Showing papers on "Vaccination published in 2004"

Prevention and control of influenza : recommendations of the Advisory Committee on Immunization Practices (ACIP)

Abstract: This report updates the 2002 recommendations by the Advisory Committee on Immunization Practices (ACIP) on the use of influenza vaccine and antiviral agents (CDC. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51 [No. RR-3]:1-31). The 2003 recommendations include new or updated information regarding 1) the timing of influenza vaccination by age and risk group; 2) influenza vaccine for children aged 6-23 months; 3) the 2003-2004 trivalent inactivated vaccine virus strains: A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like antigens (for the A/Moscow/10/99 [H3N2]-like antigen, manufacturers will use the antigenically equivalent A/Panama/2007/99 [H3N2] virus, and for the B/Hong Kong/330/2001-like antigen, manufacturers will use either B/Hong Kong/330/2001 or the antigenically equivalent B/Hong Kong/1434/2002); 4) availability of certain influenza vaccine doses with reduced thimerosal content, including single 0.25 mL-dose syringes; and 5) manufacturers of influenza vaccine for the U.S. market. Although the optimal time to vaccinate against influenza is October and November, vaccination in December and later continues to be strongly recommended A link to this report and other information regarding influenza can be accessed at http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm.

Containing Pandemic Influenza with Antiviral Agents

Abstract: For the first wave of pandemic influenza or a bioterrorist influenza attack, antiviral agents would be one of the few options to contain the epidemic in the United States until adequate supplies of vaccine were available. The authors use stochastic epidemic simulations to investigate the effectiveness of targeted antiviral prophylaxis to contain influenza. In this strategy, close contacts of suspected index influenza cases take antiviral agents prophylactically. The authors compare targeted antiviral prophylaxis with vaccination strategies. They model an influenza pandemic or bioterrorist attack for an agent similar to influenza A virus (H2N2) that caused the Asian influenza pandemic of 1957-1958. In the absence of intervention, the model predicts an influenza illness attack rate of 33% of the population (95% confidence interval (CI): 30, 37) and an influenza death rate of 0.58 deaths/1,000 persons (95% Cl: 0.4, 0.8). With the use of targeted antiviral prophylaxis, if 80% of the exposed persons maintained prophylaxis for up to 8 weeks, the epidemic would be contained, and the model predicts a reduction to an illness attack rate of 2% (95% Cl: 0.2, 16) and a death rate of 0.04 deaths/1,000 persons (95% CI: 0.0003, 0.25). Such antiviral prophylaxis is nearly as effective as vaccinating 80% of the population. Vaccinating 80% of the children aged less than 19 years is almost as effective as vaccinating 80% of the population. Targeted antiviral prophylaxis has potential as an effective measure for containing influenza until adequate quantities of vaccine are available.

Vaccination and the theory of games.

Abstract: Voluntary vaccination policies for childhood diseases present parents with a subtle challenge: if a sufficient proportion of the population is already immune, either naturally or by vaccination, then even the slightest risk associated with vaccination will outweigh the risk from infection. As a result, individual self-interest might preclude complete eradication of a vaccine-preventable disease. We show that a formal game theoretical analysis of this problem leads to new insights that help to explain human decision-making with respect to vaccination. Increases in perceived vaccine risk will tend to induce larger declines in vaccine uptake for pathogens that cause more secondary infections (such as measles and pertussis). After a vaccine scare, even if perceived vaccine risk is greatly reduced, it will be relatively difficult to restore prescare vaccine coverage levels.

A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice

Abstract: Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model.

Use of the Inactivated Intranasal Influenza Vaccine and the Risk of Bell's Palsy

Abstract: background After the introduction of an inactivated intranasal influenza vaccine that was used only in Switzerland, 46 cases of Bell’s palsy were reported. methods We conducted a matched case–control study and a case-series analysis. All primary care physicians, ear, nose, and throat specialists, and neurologists in German-speaking regions of Switzerland were requested to identify cases of Bell’s palsy diagnosed in adults between October 1, 2000, and April 30, 2001. Each physician was invited to select three control patients for each patient with Bell’s palsy, with matching according to age, date of the clinic visit, and physician. Vaccination information was provided by the physicians. results A total of 773 patients with Bell’s palsy were identified. Of the 412 (53.3 percent) who could be evaluated, 250 (60.7 percent) were enrolled and matched with 722 control patients; the other 162 patients had no controls. In the case–control study, we found that 68 patients with Bell’s palsy (27.2 percent) and 8 controls (1.1 percent) had received the intranasal vaccine (P<0.001). In contrast to parenteral vaccines, the intranasal vaccine significantly increased the risk of Bell’s palsy (adjusted odds ratio, 84.0; 95 percent confidence interval, 20.1 to 351.9). Even according to conservative assumptions, the relative risk of Bell’s palsy was estimated to be 19 times the risk in the controls, corresponding to 13 excess cases per 10,000 vaccinees within 1 to 91 days after vaccination. In the case-series analysis, the period of highest risk was 31 to 60 days after vaccination. conclusions This study suggests a strong association between the inactivated intranasal influenza vaccine used in Switzerland and Bell’s palsy. This vaccine is no longer in clinical use.

Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans.

Abstract: Protective immunity against Mycobacterium tuberculosis depends on the generation of a T(H)1-type cellular immune response, characterized by the secretion of interferon-gamma (IFN-gamma) from antigen-specific T cells. The induction of potent cellular immune responses by vaccination in humans has proven difficult. Recombinant viral vectors, especially poxviruses and adenoviruses, are particularly effective at boosting previously primed CD4(+) and CD8(+) T-cell responses against a number of intracellular pathogens in animal studies. In the first phase 1 study of any candidate subunit vaccine against tuberculosis, recombinant modified vaccinia virus Ankara (MVA) expressing antigen 85A (MVA85A) was found to induce high levels of antigen-specific IFN-gamma-secreting T cells when used alone in bacille Calmette-Guerin (BCG)-naive healthy volunteers. In volunteers who had been vaccinated 0.5-38 years previously with BCG, substantially higher levels of antigen-specific IFN-gamma-secreting T cells were induced, and at 24 weeks after vaccination these levels were 5-30 times greater than in vaccinees administered a single BCG vaccination. Boosting vaccinations with MVA85A could offer a practical and efficient strategy for enhancing and prolonging antimycobacterial immunity in tuberculosis-endemic areas.

Influenza Virus: Immunity and Vaccination Strategies. Comparison of the Immune Response to Inactivated and Live, Attenuated Influenza Vaccines

Abstract: Influenza virus is a globally important respiratory pathogen which causes a high degree of morbidity and mortality annually. The virus is continuously undergoing antigenic change and thus bypasses the host's acquired immunity to influenza. Despite the improvement in antiviral therapy during the last decade, vaccination is still the most effective method of prophylaxis. Vaccination induces a good degree of protection (60-90% efficacy) and is well tolerated by the recipient. For those at risk of complications from influenza, annual vaccination is recommended due to the antigenic changes in circulating strains. However, there is still room for improvement in vaccine efficacy, long-lasting effect, ease of administration and compliance rates. The mucosal tissues of the respiratory tract are the main portal entry of influenza, and the mucosal immune system provides the first line of defence against infection. Secretory immunoglobulin A (SIgA) and IgM are the major neutralizing antibodies directed against mucosal pathogens. These antibodies work to prevent pathogen entry and can function intracellularly to inhibit replication of virus. This review describes influenza virus infection, epidemiology, clinical presentation and immune system response, particularly as it pertains to mucosal immunity and vaccine use. Specifically, this review provides an update of the current status on influenza vaccination and concentrates on the two main types of influenza vaccines currently in use, namely the cold-adapted vaccine (CAV) given intranasally/orally, and the inactivated vaccine (IV) delivered subcutanously or intramuscularly. The commercially available trivalent IV (TIV) elicits good serum antibody responses but induces poorly mucosal IgA antibody and cell-mediated immunity. In contrast, the CAV may elicit a long-lasting, broader immune (humoral and cellular) response, which more closely resembles natural immunity. The immune response induced by these two vaccines will be compared in this review.

Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression

Abstract: The Wilms' tumor gene WT1 is overexpressed in leukemias and various types of solid tumors, and the WT1 protein was demonstrated to be an attractive target antigen for immunotherapy against these malignancies. Here, we report the outcome of a phase I clinical study of WT1 peptide-based immunotherapy for patients with breast or lung cancer, myelodysplastic syndrome, or acute myeloid leukemia. Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints. Twenty-six patients received one or more WT1 vaccinations, and 18 of the 26 patients completed WT1 vaccination protocol with three or more injections of WT1 peptides. Toxicity consisted only of local erythema at the WT1 vaccine injection sites in patients with breast or lung cancer or acute myeloid leukemia with adequate normal hematopoiesis, whereas severe leukocytopenia occurred in patients with myelodysplastic syndrome with abnormal hematopoiesis derived from WT1-expressing, transformed hematopoietic stem cells. Twelve of the 20 patients for whom the efficacy of WT1 vaccination could be assessed showed clinical responses such as reduction in leukemic blast cells or tumor sizes and/or tumor markers. A clear correlation was observed between an increase in the frequencies of WT1-specific cytotoxic T lymphocytes after WT1 vaccination and clinical responses. It was therefore demonstrated that WT1 vaccination could induce WT1-specific cytotoxic T lymphocytes and result in cancer regression without damage to normal tissues.

Projected Clinical Benefits and Cost-effectiveness of a Human Papillomavirus 16/18 Vaccine

Abstract: Background: Human papillomavirus (HPV) vaccine may be commercially available in a few years. We explored the clinical benefits and cost-effectiveness of introducing an HPV16/18 vaccine in a population with an organized cervical cancer screening program. Methods: A computer-based model of the natural history of HPV and cervical cancer was used to project cancer incidence and mortality, life expectancy (adjusted and unadjusted for quality of life), lifetime costs, and incremental cost-effectiveness ratios (i.e., the additional cost of a strategy divided by its additional clinical benefit compared with the next most expensive strategy) associated with different cancer prevention policies, including vaccination (initiated at age 12 years), cytologic screening (initiated at 18, 21, 25, 30, or 35 years), and combined vaccination and screening strategies. We assumed that vaccination was 90% effective in reducing the risk of persistent HPV16/18 infections and evaluated alternative assumptions about vaccine efficacy, waning immunity, and risk of replacement with non-16/18 HPV types. Results: Our model showed that the most effective strategy with an incremental cost-effectiveness ratio of less than $60 000 per qualityadjusted life year is one combining vaccination at age 12 years with triennial conventional cytologic screening beginning at age 25 years, compared with the next best strategy of vaccination and cytologic screening every 5 years beginning at age 21 years. This triennial strategy would reduce the absolute lifetime risk of cervical cancer by 94% compared with no intervention. These results were sensitive to alternative assumptions about the underlying patterns of cervical cancer screening, duration of vaccine efficacy, and natural history of HPV infection in older women. Conclusions: Our model predicts that a vaccine that prevents persistent HPV16/18 infection will reduce the incidence of HPV16/18associated cervical cancer, even in a setting of cytologic screening. A program of vaccination that permits a later age of screening initiation and a less frequent screening interval is likely to be a cost-effective use of health care resources. [J Natl Cancer Inst 2004;96:604 ‐15]

High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells.

Abstract: Tumor vaccines have shown promise in early clinical trials. Among them, tumor cells genetically engineered to secrete biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF) can generate a systemic antitumor immune response. Although the minimal required GM-CSF dose produced by modified tumor cells to achieve a measurable antitumor effect is well known, no data examined whether an upper therapeutic limit may exist for this vaccination strategy. Because recent data demonstrate an immunosuppressive effect of GM-CSF produced by growing tumors, we thus sought to determine whether high GM-CSF doses administered in a vaccine formulation could impair antitumor immunity. Using a vaccine strategy involving a GM-CSF-producing bystander cell line (B78H1-GM) admixed with autologous tumor, we assessed the impact of varying doses of GM-CSF while maintaining a constant antigen dose. Our results defined a threshold above which a GM-CSF-based vaccine not only lost its efficacy, but more importantly for its clinical implications resulted in substantial immunosuppression in vivo. Above this threshold, GM-CSF induced Gr1+/CD11b+ myeloid suppressor cells that substantially impaired antigen-specific T-cell responses and adversely affected antitumor immune responses in vivo. The dual effects of GM-CSF are mediated by the systemic and not local concentration of this cytokine. Myeloid suppressor cell-induced immunosuppression is mediated by nitric oxide production via inducible nitric oxide synthase (iNOS) because the specific iNOS inhibitor, l-NMMA, restored antigen-specific T-cell responsiveness in vitro. Taken together, our data demonstrated the negative impact of supra-therapeutic vaccine doses of GM-CSF and underscored the importance of identifying these critical variables in an effort to increase the therapeutic efficacy of tumor vaccines.

The Clinical Significance of Measles: A Review

Abstract: Forty years after effective vaccines were licensed, measles continues to cause death and severe disease in children worldwide. Complications from measles can occur in almost every organ system. Pneumonia, croup, and encephalitis are common causes of death; encephalitis is the most common cause of long-term sequelae. Measles remains a common cause of blindness in developing countries. Complication rates are higher in those 20 years old, although croup and otitis media are more common in those <2 years old and encephalitis in older children and adults. Complication rates are increased by immune deficiency disorders, malnutrition, vitamin A deficiency, intense exposures to measles, and lack of previous measles vaccination. Case-fatality rates have decreased with improvements in socioeconomic status in many countries but remain high in developing countries.

Influenza A Vaccine Based on the Extracellular Domain of M2: Weak Protection Mediated via Antibody-Dependent NK Cell Activity

Abstract: Vaccination of mice with a peptide corresponding to the extracellular part of M2 protein coupled to the immunodominant domain of hepatitis B core can protect mice from a lethal challenge with influenza A virus. As the extracellular part of M2 protein is highly conserved in all known human influenza A strains, such a vaccine may protect against all human influenza A strains, which would represent a major advantage over current vaccine strategies. The present study demonstrates that protection is mediated exclusively by Abs, a very important feature of a successful preventive vaccine. However, these Abs neither bind efficiently to the free virus nor neutralize virus infection, but bind to M2 protein expressed on the surface of virus-infected cells. The presence of NK cells is important for protection, whereas complement is not, supposing that protection is mediated via Ab-dependent, cell-mediated cytotoxicity. The absence of neutralizing Abs results in much weaker protection than that achieved by vaccination with UV-inactivated influenza virus. Specifically, whereas neutralizing Abs completely eliminate signs of disease even at high viral challenge doses, M2-specific Abs cannot prevent infection, but merely reduce disease at low challenge doses. M2-specific Abs fail to protect from high challenge doses, as vaccinated mice undergo lethal infection under these conditions. In conclusion, protection mediated by M2-hepatitis B core vaccine would be insufficient during the yearly epidemics, for which full protection is desirable, and overall is clearly inferior to protection achieved by immunization with classical inactivated viral preparations.

Evaluating human papillomavirus vaccination programs.

Abstract: Human papillomavirus (HPV) has been implicated as the primary etiologic agent of cervical cancer. Potential vaccines against high-risk HPV types are in clinical trials. We evaluated vaccination programs with a vaccine against HPV-16 and HPV-18. We developed disease transmission models that estimated HPV prevalence and infection rates for the population overall, by age group, by level of sexual activity within each age group, and by sex. Data were based on clinical trials and published and unpublished sources. An HPV-16/18 vaccine for 12-year-old girls would reduce cohort cervical cancer cases by 61.8%, with a cost-effectiveness ratio of $14,583 per quality-adjusted life year (QALY). Including male participants in a vaccine rollout would further reduce cervical cancer cases by 2.2% at an incremental cost-effectiveness ratio of $442,039/QALY compared to female-only vaccination. Vaccination against HPV-16 and HPV-18 can be cost-effective, although including male participants in a vaccination program is generally not cost-effective, compared to female-only vaccination.

Prevention of cervical cancer through papillomavirus vaccination

Abstract: A subset of human papillomaviruses (HPVs) promote anogenital malignancy, including cervical cancer, and prevention and treatment strategies that reflect the causal role of HPV are being developed. Vaccines based on HPV virus-like particles induce genotype-specific virus-neutralizing antibody and prevent infection with HPV1. Persistent papillomavirus infection is required for the development of papillomavirus-associated cancer and, therefore, therapeutic vaccines are being developed to eliminate established papillomavirus infection. Such vaccines test principles for the growing field of tumour-antigen-specific immunotherapy. This article reviews progress in the field and draws conclusions for the development of future prophylactic and therapeutic viral vaccines.

Single Mucosal, but Not Parenteral, Immunization with Recombinant Adenoviral-Based Vaccine Provides Potent Protection from Pulmonary Tuberculosis

Abstract: Bacillus Calmette-Guerin (BCG) vaccine has failed to control the global tuberculosis (TB) epidemic, and there is a lack of safe and effective mucosal vaccines capable of potent protection against pulmonary TB. A recombinant replication-deficient adenoviral-based vaccine expressing an immunogenic Mycobacterium tuberculosis Ag Ag85A (AdAg85A) was engineered and evaluated for its potential to be used as a respiratory mucosal TB vaccine in a murine model of pulmonary TB. A single intranasal, but not i.m., immunization with AdAg85A provided potent protection against airway Mycobacterium tuberculosis challenge at an improved level over that by cutaneous BCG vaccination. Systemic priming with an Ag85A DNA vaccine and mucosal boosting with AdAg85A conferred a further enhanced immune protection which was remarkably better than BCG vaccination. Such superior protection triggered by AdAg85 mucosal immunization was correlated with much greater retention of Ag-specific T cells, particularly CD4 T cells, in the lung and was shown to be mediated by both CD4 and CD8 T cells. Thus, adenoviral TB vaccine represents a promising novel vaccine platform capable of potent mucosal immune protection against TB. Our study also lends strong evidence that respiratory mucosal vaccination is critically advantageous over systemic routes of vaccination against TB.

Human papillomavirus vaccine acceptability among parents of 10- to 15-year-old adolescents.

Abstract: Objective. To determine human papillomavirus (HPV) vaccine acceptance among parents of 10- to 15-year-old adolescents. Materials and Methods. Five hundred seventy-five parents or guardians completed a 30-question survey regarding their knowledge of HPV and acceptance of an HPV vaccine. Afterward, subjects read an HPV educational fact sheet and completed a 26-question survey. Results were compared using the χ2 test, analysis of variance, and McNemar's test. Results. More than 60% of subjects had a general understanding of HPV. Parents opposed to the HPV vaccine were more likely to believe it would promote earlier initiation of coitus compared with parents supportive or undecided about vaccination (24%, 9%, and 6%, respectively; p = .003). Of the subjects initially opposed to or undecided about the HPV vaccine, 37% and 65%, respectively, supported HPV vaccination after an educational intervention. Conclusions. A brief educational intervention significantly improved parent's acceptance of the HPV vaccine. The negative impact of an HPV vaccine perceived as condoning early initiation of sexual intercourse seems to be minimal.

Protection of Penaeus monodon against White Spot Syndrome Virus by Oral Vaccination

Abstract: White spot syndrome virus (WSSV) occurs worldwide and causes high mortality and considerable economic damage to the shrimp farming industry. No adequate treatments against this virus are available. It is generally accepted that invertebrates such as shrimp do not have an adaptive immune response system such as that present in vertebrates. As it has been demonstrated that shrimp surviving a WSSV infection have higher survival rates upon subsequent rechallenge, we investigated the potential of oral vaccination of shrimp with subunit vaccines consisting of WSSV virion envelope proteins. Penaeus monodon shrimp were fed food pellets coated with inactivated bacteria overexpressing two WSSV envelope proteins, VP19 and VP28. Vaccination with VP28 showed a significant lower cumulative mortality compared to vaccination with bacteria expressing the empty vectors after challenge via immersion (relative survival, 61%), while vaccination with VP19 provided no protection. To determine the onset and duration of protection, challenges were subsequently performed 3, 7, and 21 days after vaccination. A significantly higher survival was observed both 3 and 7 days postvaccination (relative survival, 64% and 77%, respectively), but the protection was reduced 21 days after the vaccination (relative survival, 29%). This suggests that contrary to current assumptions that invertebrates do not have a true adaptive immune system, a specific immune response and protection can be induced in P. monodon. These experiments open up new ways to benefit the WSSV-hampered shrimp farming industry.

Effect of Vaccine Use in the Evolution of Mexican Lineage H5N2 Avian Influenza Virus

Abstract: An outbreak of avian influenza (AI) caused by a low-pathogenic H5N2 type A influenza virus began in Mexico in 1993 and several highly pathogenic strains of the virus emerged in 1994-1995. The highly pathogenic virus has not been reported since 1996, but the low-pathogenic virus remains endemic in Mexico and has spread to two adjacent countries, Guatemala and El Salvador. Measures implemented to control the outbreak and eradicate the virus in Mexico have included a widespread vaccination program in effect since 1995. Because this is the first case of long-term use of AI vaccines in poultry, the Mexican lineage virus presented us with a unique opportunity to examine the evolution of type A influenza virus circulating in poultry populations where there was elevated herd immunity due to maternal and active immunity. We analyzed the coding sequence of the HA1 subunit and the NS gene of 52 Mexican lineage viruses that were isolated between 1993 and 2002. Phylogenetic analysis indicated the presence of multiple sublineages of Mexican lineage isolates at the time vaccine was introduced. Further, most of the viruses isolated after the introduction of vaccine belonged to sublineages separate from the vaccine's sublineage. Serologic analysis using hemagglutination inhibition and virus neutralization tests showed major antigenic differences among isolates belonging to the different sublineages. Vaccine protection studies further confirmed the in vitro serologic results indicating that commercial vaccine was not able to prevent virus shedding when chickens were challenged with antigenically different isolates. These findings indicate that multilineage antigenic drift, which has not been observed in AI virus, is occurring in the Mexican lineage AI viruses and the persistence of the virus in the field is likely aided by its large antigenic difference from the vaccine strain.

Serum antibody responses after intradermal vaccination against influenza.

Abstract: Background If found to be safe and immunogenic, reduced doses of influenza vaccine given by the intradermal route could increase the number of available doses of vaccine. Methods In an open-label study, we randomly assigned 119 subjects to receive an intradermal injection of trivalent inactivated influenza vaccine, containing 6 μg of hemagglutinin for each antigen (40 percent of the usual dose), and 119 to receive an intramuscular injection of the standard dose of 15 μg of hemagglutinin for each antigen. The two groups were subdivided according to age (18 to 60 years and older than 60 years). Results Among subjects who were 18 to 60 years of age, serum antibody responses were vigorous and did not differ significantly between the intradermal and intramuscular groups, and all subjects had hemagglutination-inhibition (HAI) titers of at least 1:40. Although the subjects who were older than 60 years of age also had a vigorous antibody response, there was a trend toward a better response in the intramuscular ro...

Long-term Efficacy of BCG Vaccine in American Indians and Alaska Natives: A 60-Year Follow-up Study

Abstract: ContextThe duration of protection from tuberculosis of BCG vaccines is not known.ObjectiveTo determine the long-term duration of protection of a BCG vaccine that was previously found to be efficacious.DesignRetrospective record review using Indian Health Service records, tuberculosis registries, death certificates, and supplemental interviews with trial participants.Setting and ParticipantsFollow-up for the period 1948-1998 among American Indians and Alaska Natives who participated in a placebo-controlled BCG vaccine trial during 1935-1938 and who were still at risk of developing tuberculosis. Data from 1483 participants in the BCG vaccine group and 1309 in the placebo group were analyzed.Main Outcome MeasuresEfficacy of BCG vaccine, calculated for each 10-year interval using a Cox regression model with time-dependent variables based on tuberculosis events occurring after December 31, 1947 (end of prospective case finding).ResultsThe overall incidence of tuberculosis was 66 and 138 cases per 100 000 person-years in the BCG vaccine and placebo groups, respectively, for an estimate of vaccine efficacy of 52% (95% confidence interval, 27%-69%). Adjustments for age at vaccination, tribe, subsequent BCG vaccination, chronic medical illness, isoniazid use, and bacille Calmette-Guerin strain did not substantially affect vaccine efficacy. There was slight but not statistically significant waning of the efficacy of BCG vaccination over time, greater among men than women.ConclusionIn this trial, BCG vaccine efficacy persisted for 50 to 60 years, suggesting that a single dose of an effective BCG vaccine can have a long duration of protection.

Anti-tick vaccines.

Abstract: There is now abundant evidence that vaccination with defined protein antigens is able to induce significant immunity to tick infestation. In a limited number of cases, this immunity has been duplicated by vaccination with recombinant antigens, a critical step on the pathway to commercial vaccine production. The existence of two commercial vaccines has allowed a number of field studies showing that the existing products can make an important contribution to an integrated approach to the control of ticks in the field. Under most circumstances however, the use of a tick vaccine as the single, stand alone control technology is likely to require more efficacious vaccines than those currently available. Increases in efficacy are most likely to come through the discovery of additional, effective vaccine antigens. The number of antigens with demonstrated effect is increasing, though only slowly, while the number of potential antigens that remain to be evaluated is increasing more quickly. There is limited, though convincing, evidence that some of these antigens will show effective cross-species protection, though in a poorly understood and unpredictable way. The groundwork has been laid; the potential of the field is still to be effectively exploited.

Preventing nosocomial influenza by improving the vaccine acceptance rate of clinicians.

Abstract: Objectives: To assess the effects of interventions to prevent transmission of influenza and to increase employee compliance with influenza vaccination. Design: The change in the proportion of hospitalized patients with laboratory-confirmed nosocomial influenza was observed over time and assessed using chi-square for trend analysis. The association between nosocomial influenza in patients and healthcare worker (HCW) compliance with vaccine was assessed by logistic regression. Setting: A 600-bed, tertiary-care academic hospital. Methods: After an outbreak of influenza A at this hospital in 1988, a mobile cart program was instituted with increased efforts to motivate employees to be vaccinated and furloughed when ill as well as new measures to prevent nosocomial spread. Results: HCW vaccination rates increased from 4% in 1987–1988 to 67% in 1999–2000 (P < .0001). Proportions of nosocomially acquired influenza cases among employees or patients both declined significantly (P < .0001). Logistic regression analysis revealed a significant inverse association between HCW compliance with vaccination and the rate of nosocomial influenza among patients (P < .001). Conclusion: A mobile cart vaccination program and an increased emphasis on HCWs to receive the vaccine were associated with a significant increase in vaccine acceptance and a significant decrease in the rate of nosocomial influenza among patients.

Guillain-Barré Syndrome Following Influenza Vaccination

Abstract: ContextAn unexplained increase in the risk of Guillain-Barre syndrome (GBS) occurred among recipients of the swine influenza vaccine in 1976-1977. Guillain-Barre syndrome remains the most frequent neurological condition reported after influenza vaccination to the Vaccine Adverse Events Reporting System (VAERS) since its inception in 1990.ObjectiveTo evaluate trends of reports to VAERS of GBS following influenza vaccination in adults.Design, Setting, and ParticipantsVAERS is the US national spontaneous reporting system for adverse events following vaccination. Reports of GBS in persons 18 years or older following influenza vaccination were evaluated for each influenza season from July 1, 1990, through June 30, 2003. The number of people vaccinated was estimated from the National Health Interview Survey and US census data. Beginning in 1994, active follow-up was conducted to verify GBS diagnosis and obtain other clinical details.Main Outcome MeasureReporting rates of GBS following influenza vaccination over time.ResultsFrom July 1990 through June 2003, VAERS received 501 reports of GBS following influenza vaccination in adults. The median onset interval (13 days) was longer than that of non-GBS reports of adverse events after influenza vaccine (1 day) (P<.001). The annual reporting rate decreased 4-fold from a high of 0.17 per 100 000 vaccinees in 1993-1994 to 0.04 in 2002-2003 (P<.001). A GBS diagnosis was confirmed in 82% of reports. Preceding illness within 4 weeks of vaccination was identified in 24% of reported cases.ConclusionsFrom 1990 to 2003, VAERS reporting rates of GBS after influenza vaccination decreased. The long onset interval and low prevalence of other preexisting illnesses are consistent with a possible causal association between GBS and influenza vaccine. These findings require additional research, which can lead to a fuller understanding of the causes of GBS and its possible relationship with influenza vaccine.

Smallpox DNA Vaccine Protects Nonhuman Primates against Lethal Monkeypox

Abstract: Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.

Safety and Efficacy of Chimeric Yellow Fever-Dengue Virus Tetravalent Vaccine Formulations in Nonhuman Primates

Abstract: To construct chimeric YF/DEN viruses (ChimeriVax-DEN), the premembrane (prM) and envelope (E) genes of yellow fever (YF) 17D virus were replaced with those of each wild-type (WT) dengue (DEN) virus representing serotypes 1 to 4. ChimeriVax-DEN1-4 vaccine viruses were prepared by electroporation of Vero cells with RNA transcripts prepared from viral cDNA (F. Guirakhoo, J. Arroyo, K. V. Pugachev, C. Miller, Z.-X. Zhang, R. Weltzin, K. Georgakopoulos, J. Catalan, S. Ocran, K. Soike, M. Ratteree, and T. P. Monath, J. Virol. 75:7290-7304, 2001; F. Guirakhoo, K. Pugachev, J. Arroyo, C. Miller, Z.-X. Zhang, R. Weltzin, K. Georgakopoulos, J. Catalan, S. Ocran, K. Draper, and T. P. Monath, Virology 298:146-159, 2002). Progeny viruses were subjected to three rounds of plaque purifications to produce the Pre-Master Seed viruses at passage 7 (P7). Three further passages were carried out using U.S. current Good Manufacturing Practices (cGMP) to produce the Vaccine Lot (P10) viruses. Preclinical studies demonstrated that the vaccine candidates are replication competent and genetically stable and do not become more neurovirulent upon 20 passages in Vero cells. The safety of a tetravalent vaccine was determined and compared to that of YF-VAX in a formal monkey neurovirulence test. Brain lesions produced by the tetravalent ChimeriVax-DEN vaccine were significantly less severe than those observed with YF-VAX. The immunogenicity and protective efficacy of four different tetravalent formulations were evaluated in cynomolgus monkeys following a single-dose subcutaneous vaccination followed by a virulent virus challenge 6 months later. All monkeys developed low levels of viremia postimmunization, and all the monkeys that had received equal concentrations of either a high-dose (5,5,5,5) or a low-dose (3,3,3,3) formulation seroconverted against all four DEN virus serotypes. Twenty-two (92%) of 24 monkeys were protected as determined by lack of viremia post-challenge. This report is the first to demonstrate the safety of a recombinant DEN virus tetravalent vaccine in a formal neurovirulence test, as well as its protective efficacy in a monkey challenge model.

Effectiveness Over Time of Varicella Vaccine

Abstract: ContextReports of outbreaks of varicella in highly immunized groups have increased concern about the effectiveness of varicella vaccine.ObjectiveTo assess whether the effectiveness of varicella vaccine is affected either by time since vaccination or by age at the time of vaccination.DesignCase-control study conducted from March 1997 through June 2003.SettingTwenty different group practices in southern Connecticut.ParticipantsCase subjects, identified by active surveillance of all practices, consisted of 339 eligible children 13 months or older who were clinically diagnosed as having chickenpox and who also had a polymerase chain reaction (PCR) test result that was positive for varicella-zoster virus DNA. For each case subject, 2 controls were selected, matched by both age and pediatric practice.Main Outcome MeasuresThe effectiveness of the vaccine, especially the effects of time since vaccination and age at the time of vaccination, adjusted for possible confounders.ResultsAlthough the adjusted overall effectiveness of the vaccine was 87% (95% confidence interval, 81%-91%; P<.001), there was a substantial difference in the vaccine's effectiveness in the first year after vaccination (97%) and in years 2 to 8 after vaccination (84%, P = .003). The vaccine's effectiveness in year 1 was substantially lower if the vaccine was administered at younger than 15 months (73%) than if it was administered at 15 months or older (99%, P = .01), although the difference in effectiveness overall for children immunized at younger than 15 months was not statistically significantly different than for those immunized at 15 months or older (81% vs 88%, P = .17). Most cases of chickenpox in vaccinees were mild.ConclusionsAlthough varicella vaccine is effective, its effectiveness decreases significantly after 1 year, although most cases of breakthrough disease are mild. If administered at younger than 15 months, the vaccine's effectiveness was lower in the first year after vaccination, but the difference in effectiveness was not statistically significant for subsequent years.