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Showing papers on "Vaccination published in 1997"


Journal ArticleDOI
TL;DR: Results of this study support recommendations for vaccination against influenza of HCWs in long-term geriatric care and suggest that vaccination of frail elderly long- term-care patients may not give clinically worthwhile benefits.
Abstract: Vaccination of health care workers (HCWs) is recommended as a strategy for preventing influenza in elderly patients in long-term care. However, there have been no controlled studies to show whether this approach is effective. During the winter of 1994-1995, 1059 patients in 12 geriatric medical long-term-care sites, randomized for vaccination of HCWs, were studied. In hospitals where HCWs were offered vaccination, 653 (61%) of 1078 were vaccinated. Vaccination of HCWs was associated with reductions in total patient mortality from 17% to 10% (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80) and in influenza-like illness (OR, 0.57; 95% CI, 0.34-0.94). Vaccination of patients was not associated with significant effects on mortality (OR, 1.15; 95% CI, 0.81-1.64). Results of this study support recommendations for vaccination against influenza of HCWs in long-term geriatric care. Vaccination of frail elderly long-term-care patients may not give clinically worthwhile benefits.

615 citations


Journal ArticleDOI
TL;DR: The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib, which should substantially reduce childhood mortality due to pneumonia and meningitis.

412 citations


Journal ArticleDOI
TL;DR: The ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination, and DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.
Abstract: To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-γ (IFN-γ) production. Moreover, both the enhancement of IFN-γ production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.

378 citations


Journal Article
TL;DR: The power of DNA delivery in vivo for both the production of a new generation of more effective and targeted vaccines or immunotherapies as well as an analytic tool for the molecular dissection of the mechanisms of immune function is demonstrated.
Abstract: Recent studies support the importance of investigating a DNA vaccination approach for the immunologic control of HIV-1. In this regard, it may be important to specifically engineer immune responses in order to improve on first generation vaccine attempts. Especially for HIV, induction of cell-mediated immunity may be an important feature for any candidate vaccine. In an attempt to engineer in vivo the enhancement of cellular immune response and to direct Ag-dependent immune response from Th2 to Th1 type, we investigated the role of codelivery of genes for IL-12 and granulocyte-macrophage-CSF along with DNA vaccine formulations for HIV-1 Ag. We found that codelivery of IL-12 expression cassettes with DNA vaccines for HIV-1 in mice resulted in splenomegaly as well as a shift in the specific immune responses induced. The codelivery of IL-12 genes resulted in the reduction of specific Ab response, while the coinjection of granulocyte-macrophage-CSF genes resulted in the enhancement of specific Ab response. In addition, we observed a significant Ag-specific stimulation of T cells with codelivery of both cytokines. Most importantly, we observed a dramatic increase in specific CTL response from the group coimmunized with the HIV-1 DNA vaccine and IL-12 genes. This work demonstrates the power of DNA delivery in vivo for both the production of a new generation of more effective and targeted vaccines or immunotherapies as well as an analytic tool for the molecular dissection of the mechanisms of immune function.

371 citations


Journal ArticleDOI
22 Oct 1997-JAMA
TL;DR: Pneumococcal vaccination saves costs in the prevention of bacteremia alone and is greatly underused among the elderly population, on both health and economic grounds, and supports recent recommendations of the Advisory Committee on Immunization Practices.
Abstract: Context. —Clinical, epidemiologic, and policy considerations support updating the cost-effectiveness of pneumococcal vaccination for elderly people and targeting the evaluation only to prevention of pneumococcal bacteremia. Objective. —To assess the implications for medical costs and health effects of vaccination against pneumococcal bacteremia in elderly people. Design. —Cost-effectiveness analysis of pneumococcal vaccination compared with no vaccination, from a societal perspective. Setting and Participants. —The elderly population aged 65 years and older in the United States in 3 geographic areas: metropolitan Atlanta, Ga; Franklin County, Ohio; and Monroe County, New York. Main Outcome Measures. —Incremental medical costs and health effects, expressed in quality-adjusted life-years per person vaccinated. Results. —Vaccination was cost saving, ie, it both reduced medical expenses and improved health, for all age groups and geographic areas analyzed in the base case. For people aged 65 years and older, vaccination saved $8.27 and gained 1.21 quality-adjusted days of life per person vaccinated. Vaccination of the 23 million elderly people unvaccinated in 1993 would have gained about 78 000 years of healthy life and saved $194 million. In univariate sensitivity analysis, the results remained cost saving except for doubling vaccination costs, including future medical costs of survivors, and lowering vaccination effectiveness. With assumptions most unfavorable to vaccination, cost per quality-adjusted life-year ranged from $35822 for ages 65 to 74 years to $598487 for ages 85 years and older. In probabilistic sensitivity analysis, probability intervals were more narrow, with less than 5% probability that the ratio for ages 85 years and older would exceed $100000. Conclusions. —Pneumococcal vaccination saves costs in the prevention of bacteremia alone and is greatly underused among the elderly population, on both health and economic grounds. These results support recent recommendations of the Advisory Committee on Immunization Practices and public and private efforts under way to improve vaccination rates.

358 citations


Journal ArticleDOI
TL;DR: The addition of HIV-1 Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species, suggesting that a DNA prime/DNA plus protein boost regimen warrants active investigation as a vaccine strategy to prevent HIV- 1 infection.
Abstract: It is generally thought that an effective vaccine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses. We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cytotoxic T lymphocyte responses can be elicited in rhesus monkeys using plasmid-encoded HIV-1 env DNA as the immunogen. In the present study, we show that the addition of HIV-1 Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species. Moreover, we demonstrate in a pilot study that immunization with HIV-1 env DNA (multiple doses) followed by a final immunization with HIV-1 env DNA plus HIV-1 Env protein (env gene from HXBc2 clone of HIV IIIB; Env protein from parental HIV IIIB) completely protects monkeys from infection after i.v. challenge with a chimeric virus expressing HIV-1 env (HXBc2) on a simian immmunodeficiency virusmac backbone (SHIV-HXBc2). The potent immunity and protection seen in these pilot experiments suggest that a DNA prime/DNA plus protein boost regimen warrants active investigation as a vaccine strategy to prevent HIV-1 infection.

334 citations


Journal ArticleDOI
TL;DR: Disseminated BCG disease has historically been a disease of infants, but cases now occur in adults and older children coinfected with human immunodeficiency virus, and cases also occur after revaccination of individuals who were anergic following the initial administration of BCG vaccine.
Abstract: The attenuated bacille Calmette-Guerin (BCG) vaccine is administered to prevent tuberculosis. Complications of vaccination are uncommon. We report a new case of disseminated BCG disease and review 27 additional cases identified from a review of > 5,000 reports published between 1980 and 1996. Twenty-four of the 28 total cases were associated with an immune deficiency, including nine cases of AIDS. Seventy-one percent of the cases occurred in children younger than 2 years old. Sixty-eight percent of the patients were male. About one-half of the patients were vaccinated in a developed nation, but 85% of the cases were reported from a developed nation. Response to therapy was poor, with an overall mortality rate of 71%. We made two new observations. Disseminated BCG disease has historically been a disease of infants, but cases now occur in adults and older children coinfected with human immunodeficiency virus. Cases also occur after revaccination of individuals who were anergic following the initial administration of BCG vaccine. Disseminated BCG disease is an uncommon but devastating complication of vaccination that should be considered in the appropriate clinical setting. Immunocompromised infants and patients with late-stage AIDS are at greatest risk and respond poorly to standard therapies.

334 citations


Journal ArticleDOI
TL;DR: Preliminary design, data collection, and analytic capability of the Vaccine Safety Datalink project has been validated by replication of previous known associations between seizures and DTP and MMR vaccines.
Abstract: Objective. To fill the large “gaps and limitations” in current scientific knowledge of rare vaccine adverse events identified in recent reviews of the Institute of Medicine. Methods. Computerized information on immunization, medical outcomes, and potential confounders on more than 500 000 children 0 to 6 years of age is linked annually at several health maintenance organizations to create a large cohort for multiple epidemiologic studies of vaccine safety. Results. Analysis of 3 years of follow-up data shows that 549 488 doses of diphtheria-tetanus-pertussis (DTP) and 310 618 doses of measles-mumps-rubella (MMR) vaccines have been administered to children in the study cohort. Analyses for associations between vaccines and 34 medical outcomes are underway. Screening of automated data shows that seizures are associated with receipt of DTP on the same day (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1 to 4.0) and 8 to 14 days after receipt of MMR (RR, 3.0; 95% CI, 2.1 to 4.2). The diversity of vaccination exposures in this large cohort permits us to show that an apparent association of seizures 8 to 14 days after Haemophilus influenzae type b vaccine (RR, 1.6; 95% CI, 1.2 to 2.1) was attributable to confounding by simultaneous MMR vaccination; the association disappears with appropriate adjustment (RR, 1.0; 95% CI, 0.7 to 1.4). Conclusion. Preliminary design, data collection, and analytic capability of the Vaccine Safety Datalink project has been validated by replication of previous known associations between seizures and DTP and MMR vaccines. The diversity in vaccine administration schedules permits potential disentangling of effects of simultaneous and combined vaccinations. The project provides a model of public health-managed care collaborations in addition to an excellent infrastructure for safety and other studies of vaccines.

327 citations


Journal ArticleDOI
TL;DR: The vaccine was safe, although 15 percent of the vaccinated infants had febrile episodes (rectal temperature, >38.1°C) during the six days after the first dose, as compared with 7 percent of all the controls.
Abstract: Background Rotaviruses are the principal known etiologic agents of severe diarrhea among infants and young children worldwide. Although a rhesus rotavirus–based quadrivalent vaccine is highly effective in preventing severe diarrhea in developed countries, in developing countries its efficacy has been less impressive. We thus conducted a catchment study in Venezuela to assess the efficacy of the vaccine against dehydrating diarrhea. Methods In this randomized, double-blind, placebo-controlled trial, 2207 infants received three oral doses of the quadrivalent rotavirus vaccine (4×105 plaque-forming units per dose) or placebo at about two, three, and four months of age. During approximately 19 to 20 months of passive surveillance, episodes of gastroenteritis were evaluated at the hospital. Results The vaccine was safe, although 15 percent of the vaccinated infants had febrile episodes (rectal temperature, >38.1°C) during the six days after the first dose, as compared with 7 percent of the controls (P<0.001). ...

327 citations


Journal ArticleDOI
TL;DR: A framework of study designs is presented that relates the scientific question of interest to the choice of comparison groups, the unit of observation, the level of information available for analysis, and the parameter of effect.
Abstract: Vaccine efficacy and effectiveness (VE) are generally measured as 1 minus some measure of relative risk (RR) in the vaccinated group compared with the unvaccinated group (VE = 1 - RR). In designing a study to evaluate vaccination, the type of effect and the question of interest determine the appropriate choice of comparison population and parameter. Possible questions of interest include that of the biologic effect of vaccination on susceptibility, on infectiousness, or on progression to disease in individuals. The indirect effects, total effects, and overall public health benefits of widespread vaccination of individuals within the context of a vaccination program might also be of primary concern. The change in behavior induced by belief in the protective effects of vaccination might influence the estimates of these effects or might itself be of interest. In this paper, the authors present a framework of study designs that relates the scientific question of interest to the choice of comparison groups, the unit of observation, the level of information available for analysis, and the parameter of effect.

314 citations


01 Jan 1997
TL;DR: In this article, the authors used plasmid-encoded HIV-1 env DNA as the immunogen and showed that the addition of the HIV Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species.
Abstract: It is generally thought that an effective vac- cine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses. We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cytotoxic T lymphocyte re- sponses can be elicited in rhesus monkeys using plasmid- encoded HIV-1 env DNA as the immunogen. In the present study, we show that the addition of HIV-1 Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species. Moreover, we demonstrate in a pilot study that immunization with HIV-1 env DNA (multiple doses) followed by a final immunization with HIV-1 env DNA plus HIV-1 Env protein (env gene from HXBc2 clone of HIV IIIB; Env protein from parental HIV IIIB) completely protects monkeys from infection after i.v. challenge with a chimeric virus expressing HIV-1 env (HXBc2) on a simian immmunodeficiency virusmac backbone (SHIV-HXBc2). The potent immunity and protec- tion seen in these pilot experiments suggest that a DNA primeyDNA plus protein boost regimen warrants active in- vestigation as a vaccine strategy to prevent HIV-1 infection. Although the correlates for immune protection against HIV infection are currently unknown, it is probable that an effective HIV vaccine should elicit both strong neutralizing antibody and cytotoxic T lymphocyte (CTL) responses. Antibody re- sponses have provided protection from HIV infection in chimpanzee challenge models (1). Potential protective roles for CTL also have been recognized recently. It has become increasingly clear that CTL may play a key role in clearing viremia during primary HIV-1 infection in humans before the development of virus-neutralizing antibodies (2, 3) and in maintaining disease-free infection (4, 5). Furthermore, it has been suggested that anti-HIV CTL responses, detected in some HIV-exposed but uninfected individuals in the absence of HIV-specific antibodies, may have prevented establishment of infection (6, 7). Although a number of live vector, recombinant protein, and peptide vaccination strategies have been shown to elicit HIV- specific antibodies and CTL in nonhuman primate models and humans, it would be desirable if these responses were more potent and durable. The demonstration of the utility of plasmid DNA immunization for the induction of virus-specific CTL and neutralizing antibodies in a variety of animal disease models (8-11) suggests that this vaccine modality may prove useful for an AIDS vaccine. In fact, DNA vaccination has been shown to elicit HIV-specific CTL and antibody responses in rhesus monkeys (12-14). We recently demonstrated that im- munization regimens with HIV-1 env DNA elicit potent, long-lived envelope (Env)-specific CTL responses in rhesus monkeys (ref. 15 and unpublished work). These experiments demonstrated that (i) antigen-specific CTL responses were elicited in all monkeys after one or two vaccinations; (ii )a n additional immunization after several months of ''rest'' sub- stantially boosted CTL responses; and, (iii) these responses persisted at least 36 weeks. Although these HIV env DNA vaccines also elicited antigen-specific antibodies in monkeys, only low titers of virus-neutralizing antibodies generally were obtained (13). The full potential for the induction of HIV-specific immune responses using DNA immunization combined with other vaccine modalities has not been determined. In the present studies, we have immunized rhesus monkeys with HIV env DNA vaccines in combination with recombinant HIV-1 en- velope glycoprotein, characterized the resulting immune re- sponses, and assessed their protective efficacy against a SHIV- HXBc2 challenge.

Journal ArticleDOI
TL;DR: The whole-cell vaccine was highly immunogenic for fimbriae, pertactin, and filamentous haemagglutinin, but had a low antipertussis toxin response.

Journal ArticleDOI
TL;DR: RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children, and incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotvirus gastroEnteritis by 90% and severe gastroenterritis of all causes in youngChildren by 60%.

Journal ArticleDOI
TL;DR: Early BCG vaccination in children with atopic heredity does not seem to affect the development of atopic disease before school age, as confirmed by serology in parents of almost two-thirds of the children in each group.

Journal ArticleDOI
01 Oct 1997-Vaccine
TL;DR: Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP, this difference was less prominent before 18 months of age, the customary age for a fourth dose.

Journal ArticleDOI
TL;DR: To determine whether a protective immune response could be elicited by oral delivery of a recombinant bacterial vaccine, tetanus toxin fragment C (TTFC) was expressed constitutively in Lactococcus lactis and administered orally to C57 BL/6 mice.
Abstract: To determine whether a protective immune response could be elicited by oral delivery of a recombinant bacterial vaccine, tetanus toxin fragment C (TTFC) was expressed constitutively in Lactococcus lactis and administered orally to C57 BL/6 mice. The antibody titers elicited were lower than those following intranasal immunization (a route already known to result in high-level systemic anti-TTFC immune responses) but the protective efficacy was the same order of magnitude. The serum antibody isotypes elicited were predominantly IgG1 and IgG2a. TTFC-specific fecal IgA responses could be detected following oral or intranasal immunization. Chemically killed lactococci administered via the intranasal route were also able to elicit serum antibody responses of similar levels and kinetics to those induced by live bacteria.

Journal ArticleDOI
TL;DR: The efficacy of DDA to promote an efficient immune response is demonstrated and it is suggested that IL-12 may accelerate this development, but not change the final outcome of a full vaccination regime.
Abstract: Mice were immunized with experimental subunit vaccines based on secreted antigens from Mycobacterium tuberculosis in a series of adjuvants, comprising incomplete Freund's adjuvant (IFA), dimethyl dioctadecyl ammoniumbromide (DDA), RIBI adjuvant, Quil-A saponin, and aluminum hydroxide. Immune responses induced by these vaccines were characterized by in vitro culture of primed cells, PCR analysis for cytokine mRNA, detection of specific immunoglobulin G isotypes induced, and monitoring of protective immunity to tuberculosis (TB). The study demonstrated marked differences in the immune responses induced by the different adjuvants and identified both IFA and DDA as efficient adjuvants for a TB subunit vaccine. Aluminum hydroxide, on the other hand, induced a Th2 response which increased the susceptibility of the animals to a subsequent TB challenge. DDA was further coadjuvanted with either the Th1-stimulating polymer poly(I-C) or the cytokines gamma interferon, interleukin 2 (IL-2), and IL-12. The addition of IL-12 was found to amplify a Th1 response in a dose-dependent manner and promoted a protective immune response against a virulent challenge. However, if the initial priming in the presence of IL-12 was followed by two booster injections of vaccine without IL-12, no improvement in long-term efficacy was found. This demonstrates the efficacy of DDA to promote an efficient immune response and suggests that IL-12 may accelerate this development, but not change the final outcome of a full vaccination regime.

Journal ArticleDOI
TL;DR: Intranasal immunization of mice with PspA (pneumococcal surface protein A) or a capsular 6B polysaccharide-tetanus toxoid conjugate induced mucosal and systemic antibody responses and provided long-lasting protection against carriage of S. pneumoniae.
Abstract: Many pathogens, including Streptococcus pneumoniae, are carried asymptomatically on the nasopharyngeal mucosa and spread among individuals by close contact. Clinical disease results when pneumococci escape from the mucosa and invade sterile sites. Although systemic immunity can prevent invasive disease, control of person-to-person spread is probably dependent on immunity acting at the mucosal surface. Intranasal immunization of mice with PspA (pneumococcal surface protein A) or a capsular 6B polysaccharide-tetanus toxoid conjugate induced mucosal and systemic antibody responses and provided long-lasting protection against carriage of S. pneumoniae. Resistance to carriage was dependent on mucosal rather than systemic immunity and was effective against heterologous strains of heterologous PspA types. Intranasal immunization with PspA also protected against systemic infection following intravenous, intratracheal, and intraperitoneal challenge.

Journal ArticleDOI
Marc Lipsitch1
TL;DR: A mathematical model is analyzed designed to predict the factors affecting, and the expected extent of, serotype replacement after vaccination against H. influenzae and their implications for vaccine policy.
Abstract: Conjugate vaccines protect vaccinated individuals against both disease from and nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. Protection is specific to the capsular serotype(s) included in the vaccine. This specificity has raised concern that vaccination against particular (“targeted”) serotypes may cause an increase in carriage of (and diseases attributable to) nontargeted serotypes. I analyzed a mathematical model designed to predict the factors affecting, and the expected extent of, such replacement in the host population. The conditions for competitive exclusion and coexistence of serotypes under mass vaccination are derived, and the equilibrium carriage of target and nontarget serotypes is determined under various ecological and epidemiological conditions. The eradication threshold for a target serotype in the presence of competing, nontarget serotypes is always lower for serotype-specific than for bivalent vaccines. In a two-serotype model, the increase in the prevalence of any single nontargeted serotype due to vaccination will not exceed the total reduction in prevalence of a targeted serotype. However, if three or more serotypes interact epidemiologically, vaccination against one type may increase carriage of a second more than it decreases carriage of the first. Carriage of a second serotype against which the vaccine offers only partial protection may initially increase and then decrease as a function of vaccine coverage. I discuss the extent to which these theoretical results can account for existing data on serotype replacement after vaccination against H. influenzae and their implications for vaccine policy.

Journal ArticleDOI
TL;DR: It decimated the local population and was instrumental in the fall of the empires of the Aztecs and the Incas, and greatly affected the development of western civilization.
Abstract: More than 200 years ago, Edward Jenner performed an experiment that laid the foundation for the eradication of smallpox and transformed humankind's fight against disease. Smallpox afflicted humankind as no other disease had don; its persistence and diffusion were without parallel. The disease brought down at least three empires. Generations watched helplessly as their children succumbed to the disease or were disfigured or blinded by it. Attempts were made to contain smallpox by isolating its sufferers and, later, by using variolation with varying degrees of success. However, the definitive solution was not found until Jenner's work was done at the end of the 18th century. Milkmaids who had developed cowpox from contact with cow udders informed Jenner that they were protected from the human form of the disease; he listened to their folk wisdom and raised it to the status of scientific fact. Jenner did not discover vaccination, but he was the first to demonstrate that this technique offered a reliable defense against smallpox. It was also a reliable defense against other illnesses, such as poliomyelitis, measles, and neonatal tetanus, although this was not known in Jenner's lifetime.

Journal ArticleDOI
TL;DR: Field and experimental results supporting the fact that as a result of the induction of abortion in pregnant animals and the low degree of immunity conferred, reduced doses of Rev 1 should not be recommended as an alternative to the full standard doses are reviewed.

Journal ArticleDOI
TL;DR: The combination of increased maternal antibody titers that should result from influenza immunization and the lesser risk of influenza in the first 6 months of life allows initiation of active immunization of children after 6 month of age.
Abstract: Background.Universal immunization of children with live attenuated cold recombinant vaccine has been proposed. The renewed recommendation for maternal immunization with influenza vaccine should increase the amount of antibody transmitted to the infant and postpone the need for active immunization. T

Journal ArticleDOI
TL;DR: Found in the dorsal root ganglia, the ventral horns of the spinal cord or the affected brainstem nuclei.
Abstract: found in the dorsal root ganglia, the ventral horns of the spinal cord or the affected brainstem nuclei. As with other primary dysautonomias, the cause of the dysautonomia in the presented case was not determined. Despite extensive clinical, epizootiological and morphological investigations, mainly on feline and equine dysautonomia, the aetiology of any of these disorders is unknown. A neurotoxic agent is commonly suspected (Pollin and Griffiths 1992).

Journal ArticleDOI
01 Jun 1997-Vaccine
TL;DR: The studies described below demonstrate that DNA vaccines in reasonable dosages encoding a variety of viral proteins could result in the generation of antibodies, neutralizing antibodies, or cytotoxic T lymphocytes in primates, and these responses could be boosted by repeat administration of the DNA vaccine.

Journal ArticleDOI
TL;DR: Treatment of animals with IL-12, either alone or as a vaccine adjuvant, has been shown to prevent disease by many of the same infectious agents, by stimulating innate resistance or promoting specific reactivity.
Abstract: Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that is crucially involved in a wide range of infectious diseases. In several experimental models of bacterial, parasitic, viral, and fungal infection, endogenous IL-12 is required for early control of infection and for generation and perhaps maintenance of acquired protective immunity, directed by T helper type 1 (Th1) cells and mediated by phagocytes. Although the relative roles of IL-12 and gamma interferon in Th1-cell priming may be to a significant extent pathogen dependent, common to most infections is that IL-12 regulates the magnitude of the gamma interferon response at the initiation of infection, thus potentiating natural resistance, favoring Th1-cell development; and inhibiting Th2 responses. Treatment of animals with IL-12, either alone or as a vaccine adjuvant, has been shown to prevent disease by many of the same infectious agents, by stimulating innate resistance or promoting specific reactivity. Although IL-12 may enhance protective memory responses in vaccination or in combination with antimicrobial chemotherapy, it is yet unclear whether exogenous IL-12 can alter established responses in humans. Continued investigation into the possible application of IL-12 therapy to human infections is warranted by the role of the cytokine in inflammation, immunopathology, and autoimmunity.

Journal ArticleDOI
TL;DR: In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified, suggesting the rapid generation and selection of FMDV antigenic variants in vivo.
Abstract: A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease Four types of peptides representing sequences of foot-and-mouth disease virus (FMDV) C3 Argentina 85 were tested: A, which includes the G-H loop of capsid protein VP1 (site A); AT, in which a T-cell epitope has been added to site A; AC, composed of site A and the carboxy-terminal region of VP1 (site C); and ACT, in which the three previous capsid motifs are colinearly represented Induction of neutralizing antibodies, lymphoproliferation in response to viral antigens, and protection against challenge with homologous infectious virus were examined None of the tested peptides, at several doses and vaccination schedules, afforded protection above 40% Protection showed limited correlation with serum neutralization activity and lymphoproliferation in response to whole virus In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified This finding suggests the rapid generation and selection of FMDV antigenic variants in vivo In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveals considerable difficulties for vaccines based on synthetic peptides to achieve the required levels of efficacy Possible modifications of the vaccine formulations to increase protective activity are discussed

Journal ArticleDOI
TL;DR: Preliminary results suggest that transmission of specific pneumococcal serotypes most often associated with disease and antibiotic resistance may at least partially be controlled by immunization.
Abstract: Background.Pneumococcal nasopharyngeal colonization is important for transmission of the organisms. We assessed the ability of two tetravalent conjugate vaccines administered in early infancy to prevent carriage of vaccine-related pneumococci.Methods.A vaccine containing pneumococcal type 6B, 14, 19

Journal ArticleDOI
01 Jul 1997-Vaccine
TL;DR: The results suggest that the current recommendation for annual influenza vaccination of persons at special risk of serious disease and complications is appropriate, but that continued efforts to improve the effectiveness of the authors' prophylactic measures against influenza are needed.

Journal ArticleDOI
TL;DR: The efficacy of a PIV-3 vaccine could be demonstrated in a trial of 600 carefully monitored children vaccinated by 3 months and followed to 15 months of age, and the population size necessary to demonstrate vaccine efficacy was estimated.
Abstract: Over a 20-year period in a population of otherwise healthy children, respiratory viruses have been cultured from nasal wash specimens from each child with a clinically significant respiratory illness. Since efforts are underway to develop vaccines for prevention of illness due to parainfluenza virus (PIV) type 3, the epidemiologic characteristics of PIVs were reviewed, and the population size necessary to demonstrate vaccine efficacy was estimated. A population of 1429 children was followed through early childhood. PIVs were isolated from 286 samples, 17.4% of positive viral cultures. PIV-3 was the most common: 10% of the children had at least one symptomatic, culture-proven PIV-3 infection. PIV-3 was endemic during the study period, while the other two PIVs, PIV-1 and -2, caused biennial flu epidemics. Only four PIV-related hospitalizations were seen. The efficacy of a PIV-3 vaccine could be demonstrated in a trial of 600 carefully monitored children vaccinated by 3 months and followed to 15 months of age.

Journal ArticleDOI
TL;DR: Vine recipients were significantly more likely than were vaccine nonrecipients to indicate that influenza and its complications are very serious for high-risk patients, and it was very important for healthcare workers to receive the vaccine to decrease risk for transmission to high- risk patients.
Abstract: OBJECTIVE: To assess factors associated with influenza vaccination of healthcare workers. DESIGN: Cross-sectional survey. SETITING: University-affiliated Veterans' Affairs medical center. PARTICIPANTS: Staff physicians and nurses employed by the medical center. MEIHODS: A mailed, self-administered questionnaire. RESULTS: The response rate was 38.0%. The mean age of the respondents was 43.6 years, 71.5% were females, and 26.2% were physicians. Nearly all of the practitioners had daily or weekly contact with elderly or high-risk patients. The influenza vaccination rate of the respondents was 61.2%. More than 50% of vaccine recipients indicated that avoiding illness, protecting patients, and being able to receive the vaccine conveniently and free of charge all were very important factors influencing their decisions to receive the vaccine. Avoiding illness was rated the most important factor by 58.8% of vaccine recipients. Among vaccine nonrecipients, concern about side effects was identified as a very important factor by 36.2% and as the most important factor by 30.9%. Vaccine recipients were significantly more likely than were vaccine nonrecipients to indicate that influenza and its complications are very serious for high-risk patients. They also were more likely to report that the vaccine is very effective, that influenza vaccination is uncommonly associated with side effects, that healthcare workers' risk for contracting influenza is higher than the general public's risk, and that it is very important for healthcare workers to receive the vaccine to decrease risk for transmission to high-risk patients. After stepwise