Vaccines Have Serious Side Effects

The Revised Authoritative Guide To Vaccine Legal Exemptions

Comprehensive, authoritative information about vaccine exemptions you can trust, from Alan Phillips, J.D., a leading vaccine rights attorney with years of experience helping clients throughout the U.S. legally avoid vaccines in a wide variety of vaccine-refusal settings. Critical details for parents, students, immigrants, healthcare employees, military personnel and contractors, agencies, attorneys and clientsvirtually anyone concerned with legally avoiding vaccines in the United States. This Guide provides and explains: Important background information about the legal system; How state and federal statutes, regulations, constitutions and legal precedent interact to define the boundaries of your legal exemption rights; How to deal with local authorities and to avoid mistakes that cost others their exemption; Where legal technicalities and practical reality differand what to do about it; Read more...

The Revised Authoritative Guide To Vaccine Legal Exemptions Summary


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Monitoring vaccination studies

Assays to quantitate antigen-specific T cells are crucial for the development of cancer immunotherapy. A major issue in vaccine development is the correlation of clinical efficacy with T cell responses as surrogate markers. There is increasing evidence now from various clinical cancer vaccination trials for a relation between the detection of vaccine-induced T cells by cytokine-based assays and clinical responses (reviewed in 14). Standardization and validation of T cell assays to monitor the induction of specific T cells responses is crucial to reliable monitoring of clinical trials. Several expert workshops have been performed within the EORTC melanoma group and the International Society of Biological Therapy of Cancer (ISBTC) on T cell assay methodology and standardization (15, 16). The simultaneous use of two ex vivo T cell assays including a functional assay for T cell monitoring has been proposed (16). Controls for the quality of the samples as well as for the accuracy and...

Cancer Vaccines That Elicit

The consensus that cytotoxic T lymphocytes play a major role in tumor control led to efforts to design vaccines that specifically induce or amplify tumor-specific CTL. Key to production of such vaccines is the identification of tumor antigens recognized by CTL. In humans in particular, the vast majority of tumors arise sporadically, and the associated antigens are highly variable and difficult to predict. Early attempts to define tumor antigens based on antibody reactivity to tumor surface structures seemed of limited use, particularly once it was realized that CTL do not recognize native antigen at cell surfaces. Using these and other approaches, a large number of tumor-associated peptides have been identified (80-82). Some are derived from proteins normally expressed at low levels in a limited number of cells, but over-expressed in tumor cells. Some represent proteins (differentiation antigens) normally present only at restricted stages of development, but expressed -again, often at...

The Immune Responses Of The Primeboost Regimen With rBCGE12 AND rDISE12 Candidate Vaccine

We have started the second generation AIDS vaccine research project and successfully constructed rDIs-E12 which expressed E12 epitope under control of vaccinia p7.5 promoter in infected chicken embryo fibroblast cell. The rBCG-E12 clone that could secrete E12 epitope under control of a-antigen promoter was provided us by NIID, Japan group. The expression of a-antigen-E12 fusion protein in the both rDIs-E12 and rBCG-E12 were checked by Western blot analysis using HIV+ human serum and the size of the fusion protein was approximately 32 kDa. To test immunogenicity, we primed Balb c mice with rBCG-E12 and boosted with rDIs-E12 to analyze effect of prime-boost regimen for NT-Ab production. The ELISPOT was performed for the quantitation of antigen-specific CD8 T cells responses. We found that the E12 itself could not stimulate CTL response, it might not be CTL epitope in Balb c mice. The rBCG and rDIs vectors could stimulate CTL activity, this means CTL activity was induced with alpha...

Ist To Monitor T Cell Directed Vaccine Trials In Cancer Patients

IST is a useful tool to evaluate the induction, localization, and phenotype of antigen specific CD8+ T cells in tissues after T cell directed vaccination of cancer patients. Schrama et al. characterized the inoculation site of dendritic cell (DC) vaccination in patients with melanoma. They determined that antigen pulsed DC, but not unpulsed DC recruited and induced the local expansion of melanoma specific T cells at the inoculation site. They used MHC-multimers loaded with melanoma antigens MART, MAGE3, and gp100 and stained skin biopsies from vaccinated patients to demonstrate the specificity of the recruited and expanded T cells at the inoculation site.

What is the vaccine for MS

There seems to be a great deal of confusion in the minds of many MS patients and their families about a vaccine for MS. Some seem to think of any injectable drug as a vaccine, but this is not a correct concept. All of the medications currently approved by the FDA for chronic (long-term) use in MS are drugs but are not considered to be vaccines, although their use is to prevent periods of ill health. Interferon-beta-lb (Betaseron) and interferon-beta-la (Avonex and Rebif) and glatiramer acetate (Copaxone) are injectable drugs but are not vaccines. In contrast, a vaccine, which is generally injected, stimulates the immune system, resulting in antibody formation or a direct effect of lymphocytes against proteins or cells that have specific proteins on their surface. Several vaccines against cells in the immune system have been used in research trials.

Is there going to be a vaccine for MS

There is ongoing research into T-cell vaccines for MS. The original experiments in Europe attracted great interest. They involved injecting crude preparations of blood lymphocytes into patients in an attempt to eliminate or reduce the number of activated lymphocytes in MS patients. Ongoing studies involve a more sophisticated selection of cells to be targeted for removal by immune action. They appear to be tolerable and effective to a degree. They do not result in a long-lasting benefit. Other stalled studies attempted to induce immune tolerance without provoking a direct attack on existing cells only preliminary data on their safety have been published. No studies of this third generation type of vaccine are continuing.

Dosage And Administration Guidelines For Vaccines Available In The United States

Infants born to HBsAg-posltlve mothers (immunization and administration of 0.5 mL hepatitis B Immune globulin Is recommended for Infants born to HBjAg mothers using different administration sites) within 12 hours of birth administer vaccine at birth repeat vaccine dose at 1 and 6 months following the initial dose Vaccine Dosage

Clinical Box 52 Phytol and Vaccines

Ultrastructure Thyakoids

In immunology, an adjuvant is a substance that enhances the ability of a vaccine to stimulate an individual's specific and nonspecific immune responses. Adjuvants can increase the efficacy of a vaccine by a variety of actions, including (1) retaining the vaccine in the body or at the site of injection, (2) reducing degradation of the vaccine, and (3) recruiting macrophages and other cells to augment immune responses to a pathogen or associated antigens. Many adjuvants that are presently available can enhance the efficacy of a vaccine, but the adjuvants may also cause severe adverse inflammatory reactions. Consequently, the only adjuvant currently accepted by the Food and Drug Administration (FDA) for use in humans is aluminum hydroxide (alum). Recently, Lim and colleagues at Indiana State University have discovered that the hydrophobic phytol tail of chlorophyll and other phytol derivatives are effective and relatively safe adjuvants. This is an exciting discovery because it has the...

Avian influenza vaccine

Traditionally, vaccination has been the principal approach to protecting individuals against influenza. Currently, no influenza A H5N1 vaccine is available although several candidate vaccines are being developed. Preliminary data suggest that either higher concentrations of antigens than used in seasonal influenza vaccines and or addition of adjuvants to these vaccines will be necessary to induce protective responses 8 . Gearing production, to rapidly make necessary quantities, of such a vaccine in the event of pandemic spread will be a great challenge to the vaccine industry.

Edward Jenner Cowpox And Vaccination

In 1793, the Royal Society rejected Jenner's paper ''Inquiry into the Natural History of a Disease known in Gloucestershire by the name of the 'Cowpox.''' Five years later, Jenner published An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease Discovered in Some of the Western Counties of England, particularly Gloucestershire, and Known by the Name of the Cow Pox. Jenner named the infective cow-pox agent Variola vaccinae (Latin, vacca, meaning cow, and variola, the Latin name of smallpox). In view of the medical profession's tendency to resist new ideas and methods, the fact that Jennerian vaccination spread throughout Europe and the Americas by 1800 is as remarkable as the rewards and honors heaped upon the modest country doctor who championed the new technique. The Royal Jennerian Society was established in 1803 in order to provide free vaccinations for the impoverished children of London. To distinguish between the old practice of inoculation with smallpox...

Smallpox Inoculation Vaccination And Eradication

Variola, the smallpox virus, is a member of the orthopoxvirus family, which includes cowpox, buffalopox, camelpox, swinepox, gerbil-pox, and monkeypox. The origin of smallpox is unknown, but epidemiologists suggest that it might have evolved from one of the poxviruses of wild or domesticated animals. Based on the characteristics of the pox-viruses and genomic sequencing, virologists have suggested that smallpox and the other poxviruses might have evolved from a common ancestral virus whose natural host was a rodent. Several forms of variola, which differ in virulence, have been characterized. The complete genome of vaccinia, the virus used in vaccines that provide protection against smallpox, was decoded in 1990. Four years later, scientists Boylston's meticulous records, published in 1726 under the title An Historical Account of the Small-Pox Inoculated in New England, provided statistical evidence of the relative safety of inoculation. During the epidemic of 1721, 844 people died of...


Only four vaccination studies have been reported for shellfish. In the 1960s, Evans et al. (1968) induced bactericidin activity in the spiny lobster (P. argus), using a vaccine which consisted of killed bacteria cells. McKay and Jenkin (1969) also reported vaccine-induced immunity to bacterial challege in the Australian crayfish, Parachaeraps bicarinatus. Since these trials, two vaccines have been developed against A. viridans var. homari (gaffkemia) in American lobsters, H. americanus (Stewart and Zwicker, 1974 Keith et al., 1992 Paterson and Keith, 1992), and a Vibrio sp. NU-1 in Kuruma prawn, P japonicus (Itami et al, 1989, 1991, 1992). The vaccines against gaffkemia were developed from killed A. viridans var. homari cells, with and without supplemental vancomycin (a complex glycopeptide antibiotic active against Gram-positive bacteria). Both were effective under laboratory conditions and vaccinated lobsters showed enhanced survival in field trials. Vaccine administered by...

Vaccine development

High levels of CTL are seen in the early stages of HIV infection and the demonstration of CTL escape mutants suggests that they play a role in controlling the virus. That individuals exposed to HIV but with no evidence of infection exhibit CTL responses, reinforces the view that this type of response is important in protection. An effective vaccine might therefore contain components able to stimulate both neutralising antibody, CD4 T-cells and strong CTL responses. Clearly neither antibody- nor cell-mediated responses prevent the progression of disease in most patients, but they may delay it. However, strong pre-existing humoral and cellular immunity induced by a vaccine might still be protective. Results of vaccination experiments in monkeys and the existence of individuals who appear to be resistant to HIV infection, provide grounds for cautious optimism with regard to the feasibility of


There is considerable work being done on the development of vaccines to prevent travelers' diarrhea. Because ETECs are most frequently involved, vaccine development has been targeted at this group of organisms. Any effective vaccine would be useful not only for travelers, but even more importantly for children of the developing world where this organism is the primary bacterial cause of their diar-rheal illnesses. The vaccines being developed are to be used orally, to stimulate the local immune mechanisms of the gut. Both killed and live attenuated ETEC vaccines are being studied. For their use in travelers, vaccines would need to be given some time before travel (probably 1 to 2 weeks), and they are anticipated to provide up to 1 year or more of protection. In the developing world, they would be given to children very early in life, because this is the time when the disease is most frequent. They would probably need to be repeated at intervals after that to provide continuous...

Tuberculosis vaccine

Currently, BCG (Bacille Calmette-Guerin) is the only licensed tuberculosis vaccine. It has a number of shortcomings, among which is a relatively short period of protection, and poor antibody stimulation response beyond childhood. Since there are clearly many problems with treating TB at this point, a lot of effort and money has been focused on creation of a vaccine, as a means of preventing future infections in those at highest risk and putting a cap on the ever increasing TB epidemic. Unfortunately, it appears the obstacles in the development of such a vaccine are no less challenging than those hindering drug development. It is well know that BCG varies in effectiveness among those who receive it. This has previously been attributed to different environmental factors or differences in the BCG strains used to create the vaccine. However, a recent gene analysis has found that M. tuberculosis is genetically distinct in different parts of the world and has evolved into 6 different...

Vaccine Trials

Since the discovery that AIDS was caused by a specific retrovirus, HIV, there has been an urgent desire and effort to develop vaccines to prevent further infections. The biology of HIV poses special problems, however (Berzofsky, 1991). First, the envelope protein of HIV is highly variable, not only among strains in different infected individuals but also among strains that evolve within a single infected individual. Thus, it may be difficult to develop a vaccine that will lead to the production of neutralizing antibody that is effective against the broad range of HIV strains. Second, HIV can spread from cell to cell as well as through the blood stream. To fight cell-to-cell spread requires a cytotoxic response, mediated by cells like CD8+ cytotoxic T-lym-phocytes, as well as a humoral response (antibody production) mediated by B-lymphocytes. However, both B-lymphocytes and cytotoxic T-cells require the adequate functioning of CD4 + T-cells, known as helper T-lymphocytes (Section 1.2)....

Cancer Treatment and Research

Kirsch, Matthias, Black, Peter McL. (ed.) Angiogenesis in Brain Tumors. 2003. ISBN 1-4020-7704-1. Keller, E.T., Chung, L.W.K. (eds) The Biology of Skeletal Metastases. 2004. ISBN 1-4020-7749-1. Kumar, Rakesh (ed.) Molecular Targeting and Signal Transduction. 2004. ISBN 1-4020-7822-6. Verweij, J., Pinedo, H.M. (eds) Targeting Treatment of Soft Tissue Sarcomas. 2004. ISBN 1-4020-7808-0. Finn, W.G., Peterson, L.C. (eds) Hematopathology in Oncology. 2004. ISBN 1-4020-7919-2. Farid, N. (ed.) Molecular Basis of Thyroid Cancer. 2004. ISBN 1-4020-8106-5. Khleif, S. (ed.) Tumor Immunology and Cancer Vaccines. 2004. ISBN 1-4020-8119-7. Balducci, L., Extermann, M. (eds) Biological Basis of Geriatric Oncology. 2004. ISBN Abrey, L.E., Chamberlain, M.C., Engelhard, H.H. (eds) Leptomeningeal Metastases. 2005.

African green monkey kidney cells

Transmitted by nocturnal biting flies of the genus Culicoides. Experimentally goats are slightly susceptible but ferrets and dogs are infected more readily. Mice, rats and guinea pigs can be infected i.c. A mouse brain passage virus vaccine is effective. Virion is 75-80nm in diameter, icosahedral and similar to Bluetongue virus. Infectivity is ether-resistant but acid-sensitive, being inactivated below pH 6. Horse erythrocytes are agglutinated. Virus contains double-stranded RNA in 10 segments. Multiplies in eggs in yolk-sac, and in cell cultures of many species. Although originally confined to Africa, the virus was inadvertently introduced into Spain, and is now endemic around Madrid and other areas to the south. Synonyms African horse plague virus perdesiekte virus pestis equorum virus.

African Rift Valley fever virus See Rift Valley fever virus

200nm envelope is acquired as it buds through the plasma membrane. Survives dry at room temperature for years. Resists inactivation by some disinfectants but inactivated by 1 formaldehyde in 6 days, 2 sodium hydroxide in 24 days. Chloroform- and ether-resistant. Replicates in the chick embryo yolk-sac killing the embryo, and in cell cultures of swine macrophages, such as pig bone marrow. Hemadsorption of pig erythro-cytes is seen after 24 h and CPE later. After 100 passes the virus loses virulence for pigs but does not give protection from infection with virulent virus. Antibodies do not provide immunity. Originally observed in East, South and West Africa, the virus reached Portugal and Spain in 1957, France in 1964, Italy in 1967 and Cuba in 1971. Outbreaks occurred in Malta, Sardinia and Brazil in 1978, and Haiti in 1979. In 1982 a severe outbreak occurred for the first time in West Africa. The disease is believed to have been eradicated from Europe (except Sardinia) since 1995. In...

Clinical and Preventive Medicine 335

The Eighteenth-Century Foundations of Modern Medicine 345 Enlightenment Philosophy and Medical Reform . . . . 348 Nutrition, Malnutrition, Health, and Disease . . . . 351 Smallpox Inoculation, Vaccination, and Eradication 362 Edward Jenner, Cowpox, and Vaccination 370 The Global Eradication of Smallpox 375 Suggested Readings . . . . 380

Amplified reverse transcriptase AmpRT

Anatid herpesvirus 1 (AnHV-1) An unas-signed species in the family Herpesviridae. Differs from other her-pesviruses with respect to its structure and maturation. Mature virus particles are seen accumulated in long extensions of the endoplasmic reticulum their size varies between 160 and 380nm, and they are embedded in an osmiophilic matrix. In addition, capsids (about 80nm in diameter) and developmental stages of the viral nucleoid (about 40nm in diameter) are encountered in the nuclei of infected cells. A natural infection in domestic ducks, and possibly of mallard, Anas platyrhynchos, in the UK. There is nasal and ocular discharge, and diarrhea, with up to 97 mortality. At post-mortem examination petechial bleedings in mucosal membranes and many organs are prevalent. In less acute cases hemorrhagic or pseudomembra-nous pharyngitis, esophagitis and cloacitis are frequently observed. Typical herpesvirus particles are observed by electron microscopy in the nucleus and the cytoplasm of...

Anterior poliomyelitis virus Synonym for

Anti-idiotypes Antibodies resulting from immunization with a specific antibody (e.g. antiviral antibody). The resulting anti-idiotype antibody can have a conformation which mimics the original antigen, and so can be used itself to immunize and may induce neutralizing antibodies against the original virus. Such anti-idiotype antibodies should provide a non-infectious antigenic mass which could form the basis of a vaccine. Although protection has been demonstrated experimentally, no anti-idiotype vaccines have yet been developed.

Attachment interference See interference

Attenuated virus strains Mutant strains with low virulence or which are avirulent for their natural host species, and in which they can thus be used as a vaccine. Often obtained by passage in cell culture or in a host different from the one in which they usually cause disease.

General Non Antiretroviral

Vaccines and Immunotherapies 291 New Vaccines for Poxviruses Currently Measles, Mumps, and Rubella Vaccines 300 Varicella-Zoster Virus Vaccine 315 Influenza Virus Vaccine 318 New Developments in Influenza Vaccines 321 Hepatitis A Virus Vaccine 321 Hepatitis B Virus Vaccine 323 Rabies Virus Vaccine 326 Recent and Continuing Developments in Rabies Vaccines 330 Poliovirus Vaccines 331 Yellow Fever Virus Vaccine 336 Japanese Encephalitis Virus Vaccine 339 Adenovirus Vaccines 341 Investigational Vaccines 342 Rotavirus 342 Varicella-Zoster Virus Vaccine 345 Human Immunodeficiency Virus Vaccine 349 Herpes Simplex Virus Vaccine 352 Human Papillomavirus Vaccine 354 Cytomegalovirus Vaccine 355 Respiratory Syncytial Virus Vaccine 357 Parainfluenza Virus Vaccine 359 Other Vaccines 361

Analytic Studies Case Control Studies

Case-control studies have been extensively used in etiologic research. Their use to assess the adverse effects of drugs and other therapies is also common. Studies of the case-control design have been used with increasing frequency to evaluate the efficacy of preventive interventions (Selby et al. 1992 Weiss 1994), including vaccines (Comstock 1994). case-control studies that have evaluated the efficacy of the pneumococcal vaccine in adults (Mills and Rhoads 1996). It would be very costly and probably impossible to conduct four different cohort studies of vaccine efficacy because of the rarity of pneumococcal illness. The data from these three of the four case-control studies find a lower odds ratio for pneumococcal illness in persons who had been vaccinated, providing strong evidence for a benefit of pneumococcal vaccination in adults.

Measuring The Epidemic

Figure 1.5 The monthly infection rate (solid line) and monthly AIDS incidence (squares) in San Francisco, as estimated by Bacchetti (1990). The plot of HIV prevalence rate (percent) for homosexual and bisexual men participating in hepatitis B vaccine trials in San Francisco (triangles) is derived from data in Hessol, Lifson, O'Malley, et al. (1989). Figure 1.5 The monthly infection rate (solid line) and monthly AIDS incidence (squares) in San Francisco, as estimated by Bacchetti (1990). The plot of HIV prevalence rate (percent) for homosexual and bisexual men participating in hepatitis B vaccine trials in San Francisco (triangles) is derived from data in Hessol, Lifson, O'Malley, et al. (1989).

Possibilities for immunotherapy

Attempts at immune reconstitution have been made using interleukin 2, interferons, thymic factors or bone marrow transplantation. These have not been notably successful and remain potentially harmful, since the very factors which activate T-cells will also activate HIV replication. In vivo, activation of CD4 cells is caused by stimulation with antigens in the form of micro-organisms or vaccines. This suggests that it is sensible to treat intercurrent infections promptly and provides a rationale for prophylactic chemotherapy for pneumocystis. In some studies, vaccination (for example with influenza vaccine) has been shown to be enough of an antigenic stimulus to increase HIV replication. The advent of highly activated antiretroviral therapy (HAART) has enabled the viral load to be enormously reduced, but the difficulty of maintaining this type of therapy over long periods has led to a search for strategies to complement drug treatment. Two observations are pertinent, the first is that...

Treatment and control

As yet, there is no effective prophylactic vaccine against infection with aquatic birnaviruses, although recently several important advances have been made in this area. An excellent, concise review of the history and prospects of immunoprophylaxis against IPN has been written by Dorson (1988). The author is pessimistic about achieving an efficacious vaccine against IPN disease in salmonids for two reasons. First, the most effective method of administration of inactivated IPN vaccines is by intraperitoneal injection (Dorson, 1977 Hill and Dixon, 1977 Sano et al., 1981). This is not a viable option for the immunization of the highly susceptible fry. Although this method could be used on brood stock, it has been shown that natural carrier fish often have detectable circulating antibodies while retaining the virus in the gonads and reproductive products (Wolf et al., 1968a Yamamoto, 1975b Reno, 1976 Etchberger, 1987). Thus, it is unknown whether vaccination will confer protection against...

Topics for further study

Future studies should include the clarification of the putative picornavirus presence and its involvement in disease, comparison and grouping of all accessible isolates, improvement of serological and development of other methods for identification of virus (es). Research is also required on epizootiology (carriers, shedding mechanisms, vectors, role of farming practices, etc.) and on the immune response. Fish farmers require methods for prevention and control of GCHD, including a vaccine and a practically applicable vaccination procedure.

Suggested Readings

Smallpox Vaccine, Ahead of Its Time How the Late Development of Laboratory Methods and Other Vaccines Affected the Acceptance of Smallpox Vaccine. Berkeley, England Jenner Museum. Waterhouse, B. (1980). The Life and Scientific and Medical Career of Benjamin Waterhouse With Some Account of the Introduction of Vaccination in America, 2 vols. Edited by I. Bernard Cohen. New York Arno Press. Reprint.

Peptidemhc Tetramer Analysis

Abstract Over the past decade, the identification of tumor-associated antigens (TAAs) has allowed a novel approach to cancer therapy aimed at the induction of systemic immune responses against cancer cells through active, specific immunization. A key step in the design of effective vaccination strategies is the ability to easily and accurately determine whether the immunogen has achieved its primary goal which, in the case of anti-cancer vaccines, is the induction of TAA-specific T cells. While several methods have been utilized for this purpose, peptide MHC (pMHC) tetramers have become a particularly useful tool as they provide a flexible, rapid way to identify antigen-specific T cells directly ex vivo, and allow the characterization of their phenotype and viable isolation for further analysis. While this technology is certainly not restricted to the study of cancer-specific immune cells, for the purpose of this chapter, we will focus our discussion on this application.

Treatment and protection

Utilization of prophylactic treatments and implementation of sanitary aquacultural practices, judicious use of legal drugs and chemicals when infections occur, application of vaccines, if available, and use of genetically improved stocks are aids in health management (Plumb, 1994). Because E. tarda is a non-obligate pathogen, it is not possible to completely eliminate or totally prevent the organism's presence in most instances. For example, preventing infected animals (e.g. undesirable fish, turtles, snakes, etc.) from coming into contact with the aquaculture species is impractical, except under certain circumstances, such as closed recirculating systems. Maintaining a suitable oxygen concentration and low carbon dioxide and ammonia, reducing water enrichment and prevention of wide temperature fluctuations are basic to the health-management approach. Although these goals are difficult to attain in intensive or commercial aquaculture, they should be pursued. Immunization has become a...

Human parvovirus See B19 virus

Suckling mice are not susceptible, but transgenic mice which have been transfected with the human poliovirus receptor gene can be infected. After 1961, following the widespread use of vaccine, it was necessary to characterize virus isolates as virulent or attenuated, vaccine-derived or wild. The monkey neurovirulence test is the only one capable of assessing virulence, and transgenic mice may provide an alternative, cheaper model for vaccine testing. Sequence-based polymerase chain reaction tests can distinguish vaccine from wild strains. Two types of vaccine are available formalin-inactivated (Salk) and live-attenuated (Sabin). The widespread use of Sabin vaccine, which is given orally as a trivalent mixture of viruses attenuated by passage in cell culture (type 1, strain LSc1 type 2, strain P2712 type 3, strain Leon 12a1b), has eliminated poliomyelitis from most developed countries. No cases of poliomyelitis have been confirmed in the Americas since 1991, and the...

Hepatitisassociated antigen See Australia antigen

Simian virus strains related to but genetically distinct from the human virus have been isolated from African green and cynomolgus monkeys. An excellent formalin-inactivated vaccine is now licensed for use in people at risk for hepatitis A infection. Hepatitis B virus (HBV) Type species of the genus Orthohepadnavirus. Causes 'long incubation' hepatitis (more than 60 days). Classically, infection results from the inoculation of serum from a carrier during blood transfusion, vaccination, tattooing or ear-piercing with inadequately non-parenteral routes are also important and many cases result from domestic and sexual contact, especially homosexual practices. The complete virus is an enveloped particle 42nm in diameter, but small spherical particles 22nm in diameter and tubular forms of the same diameter but up to 100nm long, are also present in the plasma of carriers. The viral genome is 3.2kb long, and serves in infected cells as the template for a 3.4kb RNA species (pre-genomic RNA),...

Mercury Forms And Sources

Ethylmercury has received public attention because of claims that its presence in thimerosal, a preservative once used in childhood vaccines, contributed to a rise in autism 84, 114 . Experimentation on the relationship between mercury and autism is lacking, so the data pertaining to this issue are largely correlational. A relationship between vaccination and autism has been hypothesized based on the coincidence between increased vaccination and rises in the rate of autism 12, 62, 69 . However, the absence to date of a plausible common mechanism the limited bioavailability of ethylmercury, and the absence of a link in large epidemiological studies all suggest that the causes of autism lie elsewhere 3, 79, 114 .

Rifampicin See rifamycin

Cattle are less seriously affected. Herdsmen and slaughtermen often become infected and develop a biphasic illness which is usually mild, although retinal damage may occur. Buffalo, camels and antelopes may be naturally infected and die. Infection is mosquito-borne, but contact infection probably also occurs. Large mosquito-borne epizootics occurred in 1977-78 in Egypt, in 1987-88 in East Africa. Absent for a decade, it returned to Egypt in 1993. Then in 1999 a large outbreak began in the Kingdom of Saudi Arabia and Yemen, the first outbreak ever recorded outside the African continent, with more than a thousand human cases and more than 150 deaths by the end of 2000. Control is by protection from mosquitoes and by vaccination of livestock with formalin-ized or attenuated vaccines. Mice die of hepatitis when infected experimentally. Guinea pigs, ferrets and young dogs can also be infected, but birds are resistant. Virus replicates in cultures of chick, rat, mouse...

Stephen B Thacker Donna F Stroup

Public health and health care practitioners are concerned with a wide spectrum of health issues including infectious diseases, chronic conditions, reproductive outcomes, environmental health, and health events related to occupation, injuries, and behaviors. This array of problems requires a variety of intervention strategies for populations in addition to the need to provide clinical preventive services for individuals. Some critical examples are the provision of prophylactic measures (e.g., vaccination or postexposure rabies prophylaxis), educational services (e.g., public health messages to diverse populations or counseling and prophylaxis for contacts of persons with certain infectious diseases), inspection of food establishments, and control of infectious and noninfectious conditions. For these activities, the rational development of health policy depends on public health information. For example, information on the age of children with vaccine-preventable diseases has been used...

Mechanisms For Protection Of Immune Cells And Prevention Of Tumor Escape

Immune escape mechanisms utilized by malignant cells represent major obstacles in the outcome of immunotherapy in patients with malignant disease because of their multifaceted nature. Therefore, there is a need to develop strategies to counteract the immune escape mechanisms utilized by malignant cells in order to enhance the efficacy of T-cell based immunotherapies. At present, various vaccination strategies are being evaluated in phase I clinical trials. In this regard, polyvalent vaccines may be preferable to monovalent vaccines, in order to counteract the selective loss of the target antigens. Moreover, polyvalent vaccines may lead to the activation of CD4+ T lymphocytes, which appear to be an important immune component in the eradication of tumor cells (148). The choice of multivalent vaccines is also supported by the reports of beneficial effects on the clinical course of the disease in the trials conducted in patients immunized with polyvalent vaccines (149-153). However,...

Measles Edmonston virus MeV

Prodromal stage 4-5 days, followed by mounting fever, the appearance of Koplik's spots on the buccal mucosa and rash on head and neck spreading to the trunk and limbs. Recovery usually rapid but the disease can be fatal, especially in poorly nourished children. The rash is dependent on the presence of a specific immune response and is absent from certain immunodeficient patients. The patient is most infectious in the prodromal period and transmission is by airborne droplets. Respiratory complications and otitis media due to secondary bacterial infection are common. Encephalitis occurs rarely but is a serious complication with high mortality and incidence of sequelae. Subacute sclerosing panencephalitis, a rare progressive degenerative disease of the CNS, is associated with chronic infection. Virion ether-sensitive, roughly spherical, 150 nm in diameter, buoyant density in CsCl about 1.27g ml, and contains a helical nucleocapsid of about 17 x 1100nm. The...

The Interactions Between Tumor Cells And Taspecific T Cells

The hypothesis that circulating, vaccine-induced T cells may be capable to reach the tumor site and interact with tumor cells is substantiated by previous work from our laboratory. We measured by quantitative real-time polymerase chain reaction (qRT-PCR) the messenger RNA level of various cytokines supposedly produced by T cells before and during immunization. The genetic profile of individual lesions was followed by serial FNA. This study demonstrated that presence of immunization-induced T cells in the circulation correlated with increments in cytokine transcription (in particular IFN-y) during immunization compared with before. In addition, increased messenger RNA levels correlated with expression of the antigen targeted by the immunization and the localization of tHLA-staining, immunization- These findings was in agreement with earlier studies done at the National Cancer Institute, NIH in which intra-lesional localization of TA-specific T cells was noted to be necessary although...

Chum salmon reovirus Psr Psrv A

Contagious disease which only affects pigs. Causes fever, apathy, vomiting, eye discharge, diarrhea and cutaneous hemorrhages, and is frequently fatal. Secondary bacterial infection often occurs. Strains vary in virulence some are mild, others neurotropic and some are poorly neutralized by antiserum. Disease first reported in the Mid-western USA in about 1810, then in the UK in 1862, and has since spread worldwide. The pathological lesion consists of degeneration of small blood vessels causing hemorrhage. There is leukopenia, atrophy of the thymus and lymphocytic depletion of peripheral lymphoid tissues. Infection of sows 10 to 50 days pregnant may result in infection of the fetuses, abortion or congenital tremor due to cerebellar hyperplasia. Hyperimmune serum can provide passive immunity, and there are several vaccines available, attenuated in rabbits or in cell culture, that provide active immunity. However, the European Union has adopted a non-vaccination policy, and control in...

Common cold virus See human rhinoviruses

Comvax A combination vaccine containing Hemophilus B conjugate (meningococcal protein conjugate) and hepatitis B (recombinant vaccine). congenital rubella syndrome Although rubella is usually a trivial childhood exanthem, if infection occurs in utero during the first 3 months of pregnancy, 20 of infected infants are born with one or more multiple severe congenital abnormalities, including neurosensory deafness, total or partial blindness, congenital heart disease and microcephaly with mental retardation. There may also be bone translucency, retardation of growth, hepatosplenomegaly and throm-bocytopenic purpura. Vaccination of girls age 15 months against rubella as part of the MMR vaccine has resulted in a dramatic fall in congenital rubella syndrome cases since the vaccine was licensed in 1969 in the USA and 1970 in the UK.

Protection Against Other Liver Diseases

Patients with chronic HBV infection should be counseled to minimize alcohol use, although the safe level of consumption has not been defined. It is important that patients be advised to have household and sexual contacts tested for both HBsAg and HBsAb to identify both those who are infected and require further examination, and those who are susceptible to infection. Until HBsAb is documented in sexual partners, either via natural infection or vaccination, safe sex techniques must be employed. Hepatitis A (HA) vaccination is advised in all patients with chronic liver disease. Generally, screening for HA antibody is not cost effective before vaccination but may be in selected patients with a high likelihood of prior HA infection, such as those born in developing countries.

Management of Recurrent C difficile

Similar to patients with severe C. difficile infection, patients with recurrent C. difficile diarrhea have low serum antibody levels against C. difficile toxins. Treatment with normal, pooled IV gamma globulin was associated with an increased level of serum antitoxin and reduced recurrence of C. difficile diarrhea in six children with relapsing C. difficile colitis. This approach may be promising, but controlled studies are required before recommending this as a therapeutic regimen for recurrent C. difficile diarrhea. A C. difficile vaccine, based on inactivated toxins A and B, has been produced and was well tolerated and highly immunogenic in healthy volunteers. Again, controlled trials are needed to determine whether vaccination can protect susceptible individuals against C. difficile infection and colitis.

Assessment And Outlook

TCR CDR 3 analysis is a descriptive method to visualize the composition of the entire T-cell repertoire, which can be combined with other, functional readout assays of the cellular immune system. At this point, it represents a highly reproducible and high-throughput approach to gauge the T-cell repertoire in any tissue. Comparative analysis aids to compare the TCR diversity over time or in different anatomic compartments and aids to establish novel markers in the context of immunotherapy or disorders of the immune system. TCR analysis has been predominantly employed in human diseases. TCR CDR3 analysis can also be performed in murine disease models, or in non-human primates (49). The determination of the TCR repertoire may also be helpful in pre-clinical settings, i.e. in testing differences in protein or peptide composition, or vaccine formulations which affect the cellular immune response. Since T-cells are able to sense a single amino acid residue difference in antigenic peptides,...

Nonhuman primate models

The studies described above demonstrate how nonhuman primate models can be used in combination with functional genomics to understand influenza-host interactions. Our studies, in conjunction with those of others, firmly demonstrate that nonhuman primate models of influenza provide crucial information into disease progression and pathogenesis. Currently, we are focused on using functional genomics to assess the effectiveness of influenza vaccination in nonhuman primates (Baskin et al., submitted). These studies illustrate a novel use for functional geno-mics in influenza vaccine development. Genomic analyses during vaccine trials may reveal gene expression markers of protective immunity or gene expression changes that are indicative of a predisposition to a particular response to immunization and subsequent challenge.

Alexander N Zakhartchouk Qiaohua Wu and Suresh K Tikoo

Adenoviruses have become a popular vehicle for gene transfer into animal and human cells. However, wide prevalence of preexisting immunity to human adenovirus (HAdV) and the promiscuous nature of the virus have made the use of nonhuman adenoviruses an attractive alternative. Moreover, readministration of viral vectors is often required to maintain therapeutic levels of transgene expression, resulting in vector-specific immune responses. Although a number of features of bovine adenovirus (BAdV)-3 make it attractive for use as a vector in human vaccination, BAdV-3 transduces nonbovine cells, including human cells, poorly. However, genetic modification of capsid proteins (e.g., fiber, pIX) has helped in increasing the utility of BAdV-3 as a vector for transducing nonbovine cells. Here, we will describe the methods used to construct recombinant BAdV-3 expressing chimeric fiber or chimeric pIX proteins. Key Words Bovine adenovirus (BAdV)-3 pIX fiber tropism gene therapy vaccination EYFP...

The Patient And His Disease

There is an endless list of questions that patients ask, such as the influence of hormones to the disease, the risks for pregnant women, children involvement, whether there are restrictions for vaccination, whether a specific diet should be given, and so on. The information of and given by physicians also has to be improved.

Human endogenous retroviruses HERV

Human herpesvirus 1 (HHV-1) Type species of the genus Simplexvirus in the subfamily Alphaherpesvirinae. The genome DNA has been completely sequenced for the 17syn+ strain, and consists of about 150kb with a G+C of 67 . The DNA is infectious and has two components, L and S, each of which is bracketed by internal repeats. Primary infection is common in young children, often sub-clinical, but occasionally with acute stomatitis. The virus can pass along nerves and become latent in ganglia from whence it can be reactivated by non-specific stimuli (fever, sunlight, menstruation) to cause lesions, often around the mouth. Rarely, the virus may cause acute hepatitis, kerato-conjunctivitis or meningo-encephalitis. Vaccination has not been successful but treatment of kerato-conjunctivitis and skin lesions with locally applied acyclovir ointment is beneficial. In cases of encephalitis, neonatal herpes or disseminated infection, intravenous acyclovir is used. See Human herpesvirus 2. Synonyms...

Novel Method To Identify Tumorreactive T Cells Cd107 Mobilization

We developed a novel method to isolate pure, viable populations of tumor-cytolytic T cells directly ex vivo from patient blood samples using flow cytometric quantification of the surface mobilization of CD 107 - an integral membrane protein within cytolytic granules - as a marker for degranulation upon tumor stimulation (26). We showed that tumor-cytolytic T cells are indeed elicited in patients post-cancer vaccination, and that tumor-reactivity is strongly correlated with recognition efficiency of the T cells for peptide-bearing targets. Combining CD 107 mobilization with pMHC tetramer staining, we directly correlated antigen-specificity and cytolytic ability on a single-cell level to show that high recognition efficiency, tumor-cytolytic T cells represent only a minority of peptide-specific T cells elicited in patients after heteroclitic peptide vaccination (Figure 6). We have also shown that even high recognition efficiency, tumor-reactive T cells could be anergized in vivo - an...

Concentration from Sewage Water

Maini and Piva tested a series of different concentration methods for measuring adenoviruses in sewage water (10). They found no advantage in using dextran sulfate-polyethylene glycol systems, compared to alumina adsorption, for that purpose (10). Quite the opposite was found with a similar system for porcine enteroviruses by Hazlett (12), who obtained about 100-fold concentration with from 37 to full recovery. In the latter study, the concentration or adsorption, obtained with cobalt chloride, polyethylene glycol precipitation, or adsorption to aluminium hydroxide or calcium hydroxyphosphate were not satisfactory (12). Poyry used a dextran-polyethylene glycol system for the concentration of polioviruses with successful results in a study on polio vaccination in Finland (11). This method is described in Subheading 3.1.

Humoral and cellmediated immunity

Little is known about the induction of humoral and cell mediated immunity to R. salmoninarum. There is some circumstantial evidence to suggest that infected salmonids mount a protective immune response. Munro and Bruno (1988) described a natural epizootic of R. salmoninarum in Atlantic salmon, which occurred during smoltifi cation and resulted in 18 cumulative mortality. Subsequently, fish were found to be Gram- and IFAT-negative up to 69 weeks post-sea-water transfer however, 100 had agglutinin response and demonstrated a resolution of granulomatous lesions. These facts suggest that a protective immune response occurred in the survivors. Agglutinating antibodies can be induced experimentally by i.p. injection of killed R. salmoninarum however, the response is very slow (Evelyn, 1971). In general, the protection provided by vaccination with heat- or formalin-killed R. salmoninarum is limited in efficacy (Munro and Bruno, 1988 Sakai et al, 1989c). Turaga (1989) found that the best...

Newer Therapies for Food Allergy Biologic Therapy

Perhaps the most exciting developments in the field of food allergy are new therapeutic approaches that modulate immune responses to foods (Nowak-Wegrzyn, 2003). These include tolerogenic peptides, recombinant epitopes, anti-IgE and DNA vaccination, as well as administration of Th1 type cytokines, such as interleukin (IL)-12 and interferon , or strategies to antagonize the actions of Th2 cytokines, such as IL-4 and Il-5. The benefit of such approaches in food allergy was recently documented in a double blind randomized, placebo controlled, dose-ranging trial, in which a humanized monoclonal IgG1 antibody against IgE that recognizes and masks an epitope in the CH3 region of IgE responsible for binding to the FcReI on mast cells and basophils was administered subcutaneously in peanut allergic subjects (Leung et al, 2003). A statistically significant improvement (subjects increased their tolerance for peanuts from an average of 1.5 peanuts to 9 peanuts at one time) was seen between the...

Inhibitors Of Orthopoxviruses

Historical data on complication rates from the past will probably not be reliable predictors of future rates should any government undertake the vaccination of large segments of the population to deter or ameliorate the consequences of a potential terrorist use of smallpox. The world's population has changed dramatically since the middle of the twentieth century. Immunocompromised individuals comprise a much larger proportion of the overall population as a result of advances in transplantation and cancer treatment as well as the global devastation caused by HIV. In addition, the incidence of atopic dermatitis has dramatically increased in recent decades. As supplies of vaccinia immune globulin (VIG) are very limited, it may be as or even more important to identify an effective chemotherapeutic agent for the treatment of vaccinia complications as for the treatment of smallpox. Fortunately, as the viruses are closely related, most antiviral agents with activity against one of these...

Application Of Qrtpcr In Immune Monitoring Of Patients

Conclusion that peptide vaccination can result in specific reactive CTL in vivo. The findings from the molecular assay were verified in a subsequent study and were highly correlated with the results of the standard labor intensive in vitro sensitization assay (18), as well as, tetrameric HLA analysis and intracellular cytokine FACS analysis (25,26). Since then, other investigators have validated the technique for the assessment of T cell reactivities in a variety of cancers treated with varying immunization protocols including HLA matched peptides, whole proteins, and whole tumor cells (27-32). An important additional application of qRT-PCR is in the monitoring of in vivo tumors during therapy. Previously, macroscopic, microscopic and molecular changes in targeted tumor sites required resection and analysis. This approach would therefore eliminate the ability to sequentially follow an individual lesion prospectively during treatment. We have developed techniques to perform serial fine...

Mystery swine disease Lelystad virus

Myxoma virus (MYXV) The type species of the genus Leporipoxvirus. Similar to Vaccinia virus but rather more sensitive to inactivation by heat. Ether-sensitive but resistant to sodium desoxycholate. The DNA genome is 160 kb in length, G+C 40 . Antigenically similar to Rabbit fibroma virus and California rabbit fibroma virus, yet diffusion tests show a difference. Produces pocks on the CAM, but eggs are 2.5 times less sensitive than rabbit skin. Replicates and produces CPE in tissue culture of rabbit, rat, hamster and human cells also in cells of other species. Exists naturally in Uruguay and Brazil as a silent or mild infection of wild rabbits, Sylvilagus brasiliensis. Introduced into wild European rabbits, Oryctolagus cuniculus, it causes at first a severe disease, 99 fatal, with inflammation and swelling of the eyelids, nose, genital and anal openings. With passage the disease becomes endemic and less severe due to selection of resistant rabbits and attenuated strains of the virus....

Hepatitis and cholestasis

HIV infection may alter the natural history of hepatitis B infection in a number of ways. The response rate to hepatitis B vaccination is lower in HIV-infected recipients. Immunodeficiency may favour the establishment of chronic infection following acute infection and HBV replication is increased with a reduction in the rate of spontaneous loss of HBe antigen. Interferon therapy would appear to be less effective in chronic HBV HIV dual infection. The immune restoration following the initiation of antiretroviral therapy may lead to a hepatitis flare in chronic HBV carriers.

In Vitro And In Vivo Application

Multimeric MHC molecules have opened a new field not only for the analysis of antigen-specific T cells, but also to use in other applications such as expansion and isolation of antigen-specific T cells for adoptive T cell therapy. Schneck and coworkers have recently demonstrated that MHC class I-Ig dimers coated onto beads together with anti-CD28 form very potent artificial antigen-presenting cells (26). Interestingly using MHC-Ig dimers they were able to amplify CMV and MART-1 specific T cells to cell numbers at least equal to what they obtained using dendritic cells as stimulators. These amplified T cells also lysed antigen expressing tumor cells specifically. Thus, MHC-Ig dimeric molecules have now become a powerful tool in the field of tumor immunology not only for the detection of antigen specific T cells before and after different vaccination protocols but also for adoptive T cell transfer therapy. In addition, a different study has demonstrated the use of MHC class I dimers for...

Use In Clinical Trials And Furture Prospects

Considerable experience has been accumulated over the past five years on the use of tetramers to analyze patient samples in clinical trials, both in viral infections (14, 44) and cancer (13, 45, 46). A good deal of knowledge has been derived on the size, kinetics, and biology of these T cell responses. However, certain hurdles prevent the widespread use of tetramers in the clinical setting. In cancer vaccination, peptide-specific T cell responses as detected by tetramers have largely not correlated with clinical outcome (11, 45, 46). However, this issue is not unique to tetramer analysis, but applies to all methods of detecting antigen-specific T cell responses, including ELISPOT and CFC. It is becoming clear that peptide-specificity does not necessarily guarantee tumor-reactivity of a T cell response - recognition efficiency of the T cells is a key factor (26). Furthermore, T cells may be rendered non-functional or anergic in vivo, either as a consequence of direct contact with tumor...

Dissecting T Cell Function By Global Transcript Analysis

Although several groups have observed that epitope-specific immunization induces TA-specific, tumor-reactive CD8+ T cells (15 31-37), it is clear that with few exceptions (36), these immune responses are not associated with tumor regression. There are many reasons why cytotoxic, CD8+ T cells may not exert effector function at the desired site. Their number may not be sufficient, their status of differentiation or activation may not be suitable or they may not localize in the target organ. Experimental work by Kaech SM et al. (38 39) dramatically illustrates this point. These authors followed the transcriptional profile of CD8+ T cells following acute exposure to antigen in a transgenic mouse model. P14 transgenic mice that harbor P14 CD8+ T cells expressing a TCR that recognizes the GP33-41 epitope of the LCMV protein were exposed to LCMV infection and the antigen-specific CD8+ T cells harvested 8 and 40 days after. This model seems to apply very well to epitope-specific immunization...

Goals and Impacts of Health Policies

Less frequently, policies are advanced that may not be based on careful scientific consideration. For example, the 1975 campaign to immunize the American population against the swine flu was advanced without adequate consideration of the scientific evidence (Ibrahim 1985). Even though the policy was halted shortly after implementation, it led to substantial legal liability for the US government because of the potential link between swine flu vaccination and Guillain-Barre syndrome (Christoffel and Teret 1991). More recently, the ban on silicone breast implants in the United States and

Information on Health Status Risk Factors and Experiences of Populations

Since the determinants of many important public health problems are behavioral, health agencies need information that is not readily available from medical records on the prevalence of various types of behavior and on access to care. Thus, regularly conducted surveys of the general population are needed for public health surveillance. These surveys may range from large-scale assessments of the general population to assessments targeted at high-risk (i.e., particularly vulnerable) populations. This need is particularly acute at the state and local level. For example, the National Health and Nutrition Examination Survey (NHANES) (CDC 1994c) provides data to monitor changes in the dietary, nutritional, and health status of the US population. The National Health Interview Survey (NHIS) (Massey et al. 1989) is an annual cross-sectional household interview survey of the civilian, noninstitu-tionalized US population, which can be used to estimate a variety of health status measures such as...

Serotype analysis and strain characterization

Further verification that there was only one serotype of IHNV was carried out with antisera to the viral glycoprotein. The IHNV glycoprotein had been shown to be the only viral protein capable of eliciting a neutralizing antibody response in rabbits and providing protective immunity in young fish (Engelking and Leong, 1989a,b). Purified glycoprotein from IHNV-RB-1 protected the fish against challenge with a potentially lethal IHNV infection (Engelking and Leong, 1989a). The work was extended to show that the purified glycoprotein from IHNV-RB-1 also induced protective immunity against the five IHNV electropherotypes by immersion vaccination (Engelking and Leong, 1989b).

Habitat Assessment and Risk

In Maryland and Rhode Island, USA, risks at county and state level were assessed using satellite data and GIS (Glass et al., 1995 Nicholson and Mather, 1996). In Wisconsin, the distribution of human LB cases on the county level was associated with forest cover (Kitron and Kazmierczak, 1997). A risk map for Wisconsin and Illinois was developed based on canine serology and tick distribution associated with a range of environmental features (Cortinas et al., 2002 Guerra et al., 2001a,b) and can be used to target surveillance efforts and control priorities. On a continental scale, Fish and Howard (1999) provided a coarse continental map for LB risk in the USA that can be used to determine whether vaccination should be recommended or even considered. In Europe, a collaborative effort provided descriptions of LB habitats from 16 countries and these were used to associate high-risk situations with heterogeneous deciduous forest, recreational activities and diverse fauna (Gray et al., 1998).

Applications For A Novel Peptidehlagfp Complex Acquisition System

Antigen-specific T cell interactions are important components of cellular immunity to microbial agents, self-proteins, and tumor antigens. In defining these interactions, the detection and quantitative analysis of antigen-specific T cell populations has been an important step toward understanding the cellular immune response in health and disease. In this chapter, we introduce newly established system for the analyzing antigen-specific T cells, an artificial APC system which express HLA-A*201 coupled to GFP (A2GFP system) (1). A2GFP system is based on the cellular immune response between APC and CD8+ T cells. During peptide MHC recognition by T cells, membrane components of APC containing MHC class I molecules are acquired by CD8+ T cells through the TCR (2, 3). Since the acquisition of HLA-GFP peptide complexes by CD 8+ T cells is antigen-specific, and readily visualized by fluorescence microscopy and quantified by flow cytometry, we have exploited peptide HLA acquisition by T cells...

Direct Assessment Of Tcell Responses Against Tumorassociated Antigens Utilizing A Qrtpcr Assay

An immunization monitoring assay that could detect CTL (cytotoxic T lymphocytes) reactivity directly from peripheral blood, rather than after prolonged in vitro proliferation, was developed in the context of a clinical trial in which melanoma patients were vaccinated with modified peptide derivatives from the gp100 tumor antigen (17). PBMC were obtained by leukapheresis from patients before and after two cycles of peptide vaccination. Initial optimization experiments were conducted by simply exposing bulk PBMC ex vivo to the immunizing and native peptides or melanoma tumor cells. No prior in vitro sensitization or culturing of the PBMC was performed, nor were exogenous cytokines added to the cells. Because of the low overall frequency of tumor reactive CTL in bulk PBMC after immunization, changes in cytokine release after peptide elicitation were typically below the sensitivity of standard antibody detection (ELISA) assays. Therefore, real-time qRT-PCR for cytokine gene expression was...

Reports of Health Events

For some public health purposes, however, effective action requires additional detail on each case. For this reason, supplemental data collection systems have been developed for some of the diseases involved in the NNDSS. Such supplemental systems are sometimes less comprehensive in terms of the population represented but provide more detailed information on characteristics of the occurrence of disease (CDC 1991). For example, cases of hepatitis are reported weekly to NNDSS for publication in the Morbidity and Mortality Weekly Report (MMWR). In addition, the Viral Hepatitis Surveillance Project collects data on specific risk factors for different types of viral hepatitis in selected geographic areas. These data have been used to evaluate the importance of behavior associated with sexual activity and drug use as risk factors for transmitting hepatitis type B and to target educational and vaccination programs. Other uses of data may require the ability to identify the patient whose case...

Experimental Treatments and Therapeutics

Individuals receiving vaccinations with pre-aggregated Ap and an adjuvant (fol-lowedby abooster), develop antibodies that recognize Ap in the brain andvessels(Hock et al. 2002). Unfortunately, although Phase 1 trials with Ap peptide and adjuvant vaccination were not associated with any adverse events, Phase 2 trials detected complications (meningoencephalitis) in a subset of patients and were suspended (Monsonego and Weiner 2003 Masliah et al. 2005a Schenk et al. 2004 Nicoll et al. 2003 Hock et al. 2003 Bayer et al. 2005). The pathology in the index case, consistent with T-cell meningitis (Nicoll et al. 2003), was interpreted to show some clearance of Ap deposits, but some regions contained a relatively high density of tangles, neuropil threads and vascular amyloid. Ap immunoreactivity was sometimes associated with microglia, and T-cells were conspicuous in subarachnoid space and around some vessels (Nicoll et al. 2003). In another case, there was significant reduction in amyloid...

Prevention of Hepatitis B

The hepatitis B vaccine was first licensed in the United States in 1981 and is recommended for both pre- and postexposure prophylaxis. Hyperimmune globulin (HBIG) is a passive immunization that provides temporary protection and is indicated in certain postexposure situations. HBIG contains high concentrations of HB antigens, whereas regular immunoglobulin (like the one used for hepatitis A passive immunization) is prepared from plasma with varying concentrations of HB antigens. In the United States, HBIG has an HB antigen titer > 1 100,000 by radioimmunoassay. HBIG Vaccine HBIG Vaccine If a subject is exposed to HBV and was not previously immunized, a combination of HBIG and HB vaccine are recommended as depicted in Table 105-2. Two vaccines are available in the United States. For practical purposes, they are comparable in immunogenicity and efficacy rates, although the preparations are different. Recombivax-HB, manufactured by Merck Sharp & Dohme (West Point, PA) became...

Adenoviral Vectors for Infectious Disease

Recombinant adenoviral vectors for infectious diseases can generally be categorized into three general approaches. The first is the use of a vector-based vaccine where the vector encodes for proteins to achieve an immune response. In fact, adenoviruses have been used in the U.S. military for vaccines 1 . The second approach is to use adenoviral vectors, which encode immunostimula-tory genes to achieve in vivo immunotherapy. Last, these vectors can be used to provide critical accessory molecules for T- or B-cell activation for patients that are deficient in these molecules or theoretically direct anti-infectious genes such as anti-bacterial peptides. These general paradigms hold true for most gene-therapy approaches with adenoviral-based vector systems regardless if the targets are infectious disease, an inherited immune deficiency sate, or cancer. In this chapter we focus on these paradigms in the context of specific disease entities that may be candidates for treatment with...

The Future for Management of Lyme Borreliosis

An integrated approach to the control of LB is at an early stage of development, with the objective of lowering tick densities and reducing the proportion of ticks infected with B. burgdorferi s.l. The choice of intervention strategies used in an integrated programme within a disease-endemic community will depend on the level of engagement by that community. Not all methods may be applicable or acceptable to a specific target population. Some interventions only require the participation of individual households while others will require the cooperation of the entire community. Interventions such as the vaccine or personal protection measures will only reduce risk for the individual practising such behaviours. The application of acaricides to the environment or tick hosts may benefit neighbouring properties and visitors to the treated properties. Current technologies, properly applied, clearly could reduce the incidence of LB. Nevertheless, utilization of existing technology,...

PCR See polymerase chain reaction

Peptide vaccines Synthetic peptides were produced initially in 1963, and thought to have great promise as vaccines as the development of gene sequence analysis led to precise descriptions of the amino acid sequences of presumed antigenic binding sites (epitopes). Although clear evidence was obtained that protection against a major animal pathogen, foot and mouth disease virus, could be obtained by peptide immunization, albeit only at very high peptide doses in cattle, Meloen RH et al (1995) Vaccine 13, 885

Prevention and Treatment of Acute Hepatitis C

There are no vaccines available to prevent acute hepatitis C. The only way to effectively prevent it is to eliminate exposure to risk factors. No firm recommendation can be made for postexposure prophylaxis for hepatitis C. Study results are equivocal. Some experts recommend administration of Ig (0.06 mg kg) after a bonafide percutaneous exposure. The immunoglobulin should be administered as soon as possible. However, work in animal models (chimpanzees) has shown a lack of protectiveness when animals that received prophylaxis with immunoglobulin were challenged with HCV. Moreover, available data show that in humans the neutralizing antibody evoked after infection with HCV is short lived and does not protect against reinfection. Passive immunoprophylaxis for hepatitis C appears to be inefficient. To date, there is no effective vaccine against HCV infection, possibly because of the extensive genetic and antigenic diversity among HCV strains, the absence of natural immunity after...

Polyneuropathy and chemotherapy

Toxic neuropathies caused by chemotherapy are usually dose-dependent, and have a potential reversibility after termination of the drug treatment. Little is known about the influence of preexisting polyneuropathies in the development of a chemotherapeutically induced neuropathy (except vincristine given in patients with hereditary sensorimotor neuropathy), and the toxicity of only a few drug combinations have been described. This is of importance as chemotherapy is not always used as a single agent therapy, but patients often receive drug combinations or second line therapy. Additionally also biological agents such as antibodies, interferons, cytokines and vaccines are used in cancer therapy and also have a risk of inducing polyneuropathies.

Unwilling but essential test subjects

While it has long been, and continues to be, a subject that can invoke the expression of strongly-held opinions, it seems to be an unavoidable reality that without animal research we would know far less today about biological systems and the many illnesses that afflict human beings and other animals. While animals should only ever be used when there is realistically no other known alternative, and should be treated with humane respect to create a minimum of avoidable suffering, medical researchers have stated that the historical use of animals in medical tests has enabled them to find new and ever-better treatments for diseases such as cancer and antibiotics for infections. The scientific community also believes that these tests have helped radically improve surgical techniques, and aided in the development of vaccines for a vast number of deadly and debilitating viruses. Over many years, animals have unwillingly served as surrogates for human beings in procuring vital information...

Control and treatment

Data on predisposing factors are limited to water temperature. Non-specific prevention methods are not known. Breeding for resistance, using G. rarus as a model, was suggested by Wang et al. (1994). Immunization seems to be a promising approach for prevention. Injection of an inactivated virus prepared from infected tissue induced a relatively long-lasting, specific, protective immunity (Nie and Pan, 1985). Methods of large-scale virus production were improved (Yang et al., 1992 Ye et al., 1992 Luo et al., 1993) and the selection of a virus strain for the vaccine was also reported (Luo et al., 1993). Zhu et al. (1993) found that the 'Kelieao-Yufukang', a combination of two drugs, possessed in vitro and in vivo anti-GCRV activity.

Action after exposure to HBV and HCV

The greatest risk of acquiring a BBV infection from a needlestick injury comes from HBV E antigen positive, and surface antigen positive patients. If injury occurs, the recipient should have their antibody profile checked. High responders are at no risk. Low responders should receive a booster dose of vaccine and non-responders should receive HBV immunoglobulin HBV transmission can be prevented if immunoglobulin is given within 48 hours.

Host response to infection

Efforts over the last 10 years to improve the effectiveness of vaccines against furunculosis have led to a much improved understanding of the salmonid immune system, and a number of comprehensive reviews have been published (Warr and Cohen, 1991 Secombes, 1994a Secombes and Olivier, 1997). In general, most components of the fish immune system are analogous to those of higher vertebrates. These include physical barriers and chemical barriers to prevent infection, inducible but non-specific humoral factors, phagocytes and non-specific cytotoxic cells, which mediate an inflammatory response, and, finally, specific immunity, effected by lymphocytes. It is this last type that is responsible for 'immunological memory', ensuring that responses to a second exposure are faster and stronger than the initial response, thus conferring immunity (Secombes and Olivier, 1997). Specific immune responses include both humoral immunity, based on the production of antibodies by B cells, and cellular...

Current research and the future

The rapidly increasing evidence on viral involvement in AIDS-associated malignancies suggests novel molecular targets for drug discovery using drug screening and molecular modelling. Vaccines for cancers occurring in patients with human papilloma viruses associated with cervical and ano-genital carcinoma and EBV in haematological malignancies are currently being researched. Other therapeutic approaches include biological therapy (for example IL-2, IL-12, IFN-a), immune-based therapy (for example antigen-presenting cells and monoclonal antibodies against B-cell targets) and angiogenesis inhibitors.

Jaagsiekte sheep retrovirus JSRV

Replication also occurs in cell cultures of chick and various mammalian tissues, as well as mosquito cells. Causes encephalitis on i.c. injection of mice, hamsters and monkeys. Inactivated vaccine is used in Japan, Korea, Taiwan and China. In Japan and China an attenuated vaccine is now licensed and is very effective. The attenuated vaccine in Japan is used only for pigs.

Callitrichine herpesvirus 2 CalHV2 An

Camelpox virus (CMLV) A species in the genus Orthopoxvirus. Causes pustules around the lips and nose of camels, and sometimes keratitis. Usually mild but may be severe, causing abortions and up to 25 mortality, especially in young animals. Incubation period 4-15 days. Epidemics occur every 3-5 years in camels in the Middle East, N Africa, Pakistan and the former southern USSR. May cause lesions on the hands of camel drivers. Lesions produced on the CAM are very similar to those caused by Variola virus but in cell cultures giant cells are produced. Has a very limited host range. The attenuated MVA strain of Vaccinia virus can be used as an effective vaccine. Synonym photo-Shootur virus. Canarypox virus (CNPV) A species in the genus Avipoxvirus. Similar to Fowlpox virus. Causes a fatal infection in canaries, with pneumonia and exudate over serous membranes. Sparrows are susceptible, chickens usually not. A vaccine strain is under development as a candidate human vector vaccine. The...

Treatment Of Adolescents

When treating adolescents there are some important considerations the patient's age and weight can affect the dose of the drug for example, the dose of hepatitis B vaccine is different for under-15s from the dose for adults. Some drugs may have particular side-effects, making them unsuitable for teenagers for example, doxycycliney's effects on teeth and bone development. The dosing and administration of treatment should be carefully considered so that

In Situ Mhc Tetramer Staining

Abstract With the onset of MHC tetramer technology came a wealth of new understanding of antigen specific CD8+ T cells. This chapter discusses the application of MHC tetramer technology to stain antigen specific T cells in tissue sections. In situ tetramer staining (IST) can be used to determine the localization, abundance, and phenotype of antigen specific T cells in their native environment. IST can be used to stain essentially any antigen specific T cell in any tissue for which MHC tetramers are available. In this chapter, an overview of the technique is described including advantages and disadvantages of using thick fresh sections vs. thin frozen sections, and using direct labeling vs. indirect labeling. A summary of experimental systems that have employed IST to gain understanding of antigen specific CD8+ T cells is provided, including some interesting biology that has been revealed from these studies. Finally, the prospects for using IST to evaluate cancer specific T cells in...

Branched Peptides or Peptide Dendrimers

Synthetic branched polypeptides were introduced by Hudecz and coworkers (see 43 for a review) in the early 1980s. They have emerged as a new class of artificial proteins with potential biomedical application, particularly in vaccine design and serodiagnosis. They were based on a poly Lys-(DL-Ala3) backbone. Since then, several variations of branched peptides have been developed, which differ only in the design of the core matrix (Fig. 9.1). Some can be produced by classical solid-phase synthesis methods, such as the multiple antigen peptide (MAP) system, whose core contains two or three levels of geometrically branched lysine residues 44 the template-assembled synthetic protein (TASP), whose core template is made of linear or cyclic peptides with lysine side chains for peptide anchoring 45 and, more recently, a sequential oligopeptide carrier (SOCn) formed by the repetitive Lys-Aib-Gly moiety 46 . Such branched peptides are also known as peptide dendrimers 47 .

Further treatment for upper airway conditions

This is now a rare condition in countries where HiB immunisation has been introduced. However, it does still occur, in an older age group, in cases of vaccine failure and in unimmunised children. Once the airway has been secured, blood should be sent for culture and treatment with intravenous cefotaxime or ceftriaxone commenced. With appropriate treatment, most children can be extubated after 24-36 hours and have recovered fully within 3-5 days. Complications such as hypoxic cerebral damage, pulmonary oedema and other serious Haemophilus infections are rare but in the under two year old, immunity is not secure and there are cases of secondary HiB meningitis occurring after successful treatment of epiglottitis. In countries where the HiB vaccine is in use there should be an investigation into vaccine failure.

Understanding senescence and the maintenance of proliferative capacity

Understanding protective immunity is the gateway to vaccine development. Long term immunological protection is likely to depend on both the quantity and the quality of the antigen specific CD4+ and CD8+ T-cells that are generated. The level of antigen provided and the manner of presentation do certainly impact on both these parameters. However what defines exactly these parameters and how to govern them are not known yet. Although we are becoming better at inducing antigen specific T-cell responses in vivo using various vaccine strategies (e.g. antigen with adjuvants, antigen presenting dendritic cells, recombinants viral vectors, DNA), interrogation and controversy still remain as regards which are the most relevant T-cell phenotypic subpopulations or functional characteristics (i.e. effector functions as well as T-cell receptor usage and affinity - avidity) to generate. The path is still long before we reach a complete understanding of all T-cell mediated immunity mysteries the...

Strategies For Improving Systemic Therapy

An exciting new area is the identification of several specific targets for novel therapeutic approaches based on an understanding of the molecular genetic and biochemical features of the tumor. These therapeutic approaches may include monoclonal antibodies either alone or conjugated to a cytotoxic substance vaccines or gene therapy to either suppress an oncogene or replace the product of an inactivated tumor suppressor gene.58 These strategies may be combined with current chemotherapy regimens to produce a synergistic effect. Antibodies against the HER-2 neu and epidermal growth factor receptor oncogene products have been demonstrated to have a synergistic effect when combined with cisplatin, doxorubicin, and cyclophosphamide.59,60 Novel therapies may also be used to protect normal cells against the effects of chemotherapy drugs and thus lessen side effects. For example, gene therapy may allow the human multidrug-resistance gene to be transfected into human marrow progenitors to...

Suggestions For Further Study

Factors and tolerance thresholds that precipitate susceptibility to specific pathogens are not known, and development of optimal husbandry techniques for different shellfish species, age classes and environmental holding conditions should be a priority. Alternative treatments to broad-spectrum antibiotics are required, and this may be achieved by more research into vaccines and or mechanisms to stimulate the immune system in shellfish.

Etiology And Pathophysiology

Conditions for anaerobic organisms may lead to the development of tetanus. Occasionally, no apparent portal of entry can be established. Sources of infection that have been incriminated include the alimentary tract, tonsils, ear lesions, as well as contaminated vaccines, sera, and catgut (7,8).

Transmissible gastroenteritis of pigs virus

A species in the genus Coronavirus, with worldwide distribution. Causes a commonly fatal disease of young pigs and occasionally has infected dogs. There is diarrhea, vomiting, dehydration and death after 5-7 days. In pigs over 3 weeks there is more chronic diarrhea but recovery is usual. Virus replicates in the small intestine and can be demonstrated in the feces by electron microscopy. Infectivity survives drying at room temperature for 3 days. Spread by direct and indirect contact starlings may play a role in the mechanical spread. Replicates in pig kidney cell cultures. An inactivated vaccine prepared in dog cell cultures has been used. Colostrum from recovered sows protects the young. There appears to be only one antigenic type. Synonyms transmissible gastroenteritis of pigs virus porcine respiratory corona-virus.

Bovine viral diarrhea virus 1 BVDV1 A

The virus may cross the placenta, causing abortion or fetal abnormalities. Infection of the fetus with a non-cytopathic strain before development of immunological competence (110 days' gestation) can result in the animal being persistently infected with BDV for life. It is these animals that maintain the virus in the population, and that may develop severe mucosal disease which develops in such persistently infected cattle when they become infected with a second cytopathic strain of BDV. The disease is often mild and antibodies may be present in most members of a herd. Antibodies not found in humans or horses. A related virus occurs in sheep in southern Germany and pigs in Australia. Serial passage in rabbits leads to attenuation of virulence for cattle and this virus may be used as a vaccine. There are probably at least seven antigenically distinguishable types of the virus. It is spherical, 57nm in diameter with a 24nm wide core, and envelope without projections. Infectivity...

Tests for antiHIV1 and HIV2

Anti-HIV tests have transformed our understanding of the epidemiology of AIDS in the years since they were introduced in 1984, and they are still the bedrock of clinical diagnosis and much epidemiological research. Anti-HIV appears three weeks to three months after exposure to HIV and thereafter is invariably detectable in spite of any detrimental effect the virus may have on lymphocyte function and therefore antibody production. Neutralising antibodies to HIV are also measurable, but their titres are low. An inability to mount a neutralising response to HIV antigens together with the mutability of the virus are the most likely reasons why conventional approaches to preparing a vaccine have so far failed.

Supplemental Reading

N Engl J Med 1975 292 933-6. Kean, BH, Waters S. Diarrhea of travelers. I. Incidence in travelers returning to United States from Mexico. AMA Arch Indust Health 1958 18 148-50. Merson MH, Morris GK, Sack DA, et al. Travelers' diarrhea in Mexico a prospective study of physicians and family members attending a congress. N Engl J Med 1976 294 1299-305. Peltola H, Siitonen A, Kryonseppa H, et al. Prevention of travelers' diarrhea by oral subunit whole-cell cholera vaccine. Lancet 1991 338 1285-9. Sack RB. Diarrhea producing factors in cultures of Escherichia coli. Proceedings of the 4th Joint Conference, Japan-USS Cooperative Medical Science Program 1968 23-9. Sack RB. Travelers' diarrhea microbiologic basis for prevention

Viral Gastroenteritis

Rotavirus is estimated to cause 800,000 deaths per year around the world (Parashar et al, 1998). Almost all children suffer an infection with rotavirus by the age of 5 years many of these infections result in hospitalization or death. Disease is generally milder in adults. The incubation period is approximately 2 days, and vomiting, diarrhea, crampy abdominal pain, and fever characterize the clinical illness. A specific diagnosis can be established with rapid antigen detection on stool specimens. Treatment is supportive. A live, oral, tetravalent rotavirus vaccine (RRV-TV, RotaShield) was withdrawn from the market in the fall of 1999 after it was associated with intussusception (Dennehy and Bresee, 2001).

Safety Assessment Versus Efficacy Assessment

Abstract Many statistical methods have been developed that focus primarily on efficacy. Safety evaluation frequently involves many additional considerations. Randomized controlled trials, especially later phase 3 trials, are infrequently designed based on safety outcomes. Most of these trials are designed based on efficacy outcomes, and therefore have limited power to detect important differences in safety outcomes. Recently, there have been calls to design trials with sufficient power to address known safety concerns. When prevention trials introduce an experimental preventive intervention (e.g., a vaccine) to an otherwise healthy (although at-risk) population, safety considerations can substantially affect the benefit risk ratio and thus the utility and acceptability of the intervention. Observation of safety outcomes is often less controlled than for efficacy outcomes, particularly for safety concerns that emerge during the course of the trial. When either safety or efficacy...

Preparation of Purified Virus Material

The aqueous polymer extraction method has been utilized for the preparation of a Foot-and-Mouth disease virus vaccine (13,14). It was used for purification of Venezuelan equine encephalitis virus (VEE) and the material used to establish an enzyme-linked immunosorbent assay (ELISA) for detection of VEE antibodies in human and animal sera (15,16). The high purity was obtained by a three-step extraction procedure in which the virus was alternatively partitioned to the bottom and top phase. A similar procedure has been discussed by Philipson et al. (17) and Norrby and Albertsson (18).

Cell cultivation in vitro

Cultivation of cells in vitro belongs to the standard pool of techniques available not only in cellular immunology, but also in physiology, anatomy, histology, virology, molecular genetics, and biochemistry. In addition, the development of tissue culture as a modern technique helped to engender significant knowledge in the production of vaccines and in an understanding of neoplasia. In addition to its major advantages, such as the ability to control the environment, homogeneity of samples, and economy of cultivation, one must keep in mind the several disadvantages inherent in this technique. To cultivate the cells in vitro, the cells were dissociated from a three-dimensional network and from various types of intra-cellular cooperation. Thus, the validity of the cultured cells as a model of physiological function in vivo has often been criticized.

Canine adenoviruses 1 and 2 CAdV1 and

-2) Two serotypes of Canine adenovirus, a species in the genus Mastadenovirus. A natural infection of dogs, often silent, but in puppies there is often fever, vomiting and diarrhea with up to 25 mortality. There is cutaneous edema, ascites, hemorrhages into the viscera and hepatitis. Also a cause of laryngotracheitis (kennel cough). In foxes there is acute encephalitis and hemorrhage into the brain. Spread of infection is from the respiratory tract and urine. Experimentally, dogs and foxes may be infected by any route. Bears, coyotes, wolves and raccoons are susceptible. Virus replication with CPE occurs in cultures of dog, ferret, raccoon and pig cells. Hemagglutination is reported. A modified live vaccine, attenuated by passage in pig kidney cell cultures, produces solid immunity following a single dose in dogs of any age. The complete DNA sequence of canine adenovirus 1 has been determined. There was little identity to human adenoviruses in the early region genes, more in the late...

NP cells See nonproducer NP cells

Oka vaccine virus An attenuated Japanese strain of varicella-zoster virus, the basis Oka vaccine virus of a licensed vaccine against chickenpox (Varivax ), which appears to provide long-term cell-mediated and humoral immunity, although breakthrough infections after exposure to wild-type VZV are occasionally seen in vaccinees. The vaccine has also been shown to cause herpes zoster in up to 6 of immunocompro-mised vaccinees, such as children with leukemia. After more than 20 years experience with the vaccine in Japan, it was licensed and recommended for use in the US in 1995. The genome DNAs of Oka vaccine and wild-type virus can be readily distinguished by a PCR-based test.

Equine encephalosis viruses 17 EEV17

Species in the genus Lentivirus causing acute or chronic infections in horses. The disease was first described in 1843. Incubation period 12-15 days or longer. There are acute episodes with fever, anemia, nasal discharge and subcutaneous edema. Remissions occur which may last for years but the infection is usually fatal. Viremia may be present for years, even during remissions. Transmission to other species is reported but not confirmed. Insect vectors, probably mechanical, are suspected but contact infection is possible as virus is present in milk, semen, saliva and urine. Control is by slaughter as there is no vaccine of proved efficacy. The RNA genome is 8.2kb in length, and the DNA provirus includes LTRs of 321 nucleotides at each end. The virion is 80-120nm in diameter, enveloped, possibly with small projections. Agglutination of fowl, frog and human erythrocytes by serum of infected horses is reported. Strains can be distinguished by virus

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