2005 ACIP recommendations effect on newborn hepatitis B vaccination rates and the factors affecting the successful implementation of the recommendations in the US

Background. Hepatitis B virus infection is one of major causes of acute and chronic hepatitis, cirrhosis of the liver, and primary hepatocellular carcinoma. Hepatitis B and its long term consequences are major health problems in the United States. Hepatitis B virus can be vertically transmitted from mother to infant during birth. Hepatitis B vaccination at birth is the most effective measure to prevent the newborn from HBV infection and its consequences, and is part of any robust perinatal hepatitis B prevention program following ACIP recommendations. Universal vaccination of the new born will prevent HBV infection during early childhood and, assuming that children receive the three dosages of the vaccine, it will also prevent adolescent and adult infections. Hepatitis B vaccination is now recommended as part of a comprehensive strategy to eliminate HBV transmission in the United States. ^ Objective. (1)To assess if the hepatitis B vaccination rates of newborn babies have improved after the 2005 ACIP recommendations. (2) To identify factors that affects the implementation of ACIP recommendation for hepatitis B vaccination in newborn babies. These factors will encourage ongoing improvement by identifying successful efforts and pinpointing areas that fall short and need attention. Additional focus areas may be identified to accelerate progress in eliminating perinatal HBV transmission.^ Methods. This review includes information from all pertinent articles, reviews, National immunization survey (NIS) surveys, reports, peer reviewed literature and web sources that were published after 1991.The key words to be used for selecting the articles are: "Perinatal Hepatitis B Prevention program", "Universal Hepatitis B vaccination of newborn babies", "ACIP Recommendations." The data gathered will be supplemented with an analysis of vaccination rates using the National Immunization Survey (NIS) birth dose coverage data.^ Results. The data collected in the NIS of 2009 reveals that the national coverage for birth dose of HepB increased to 60.8% from 50.1% in 2006. The largest increase observed for the birth dose in the past 5 years is from 2008 which increased from 55.3 % to 60.8% in 2009. By state, coverage ranged from 22.8% in Vermont to 80.7% in Michigan. %. Overall, in 2009 the estimated vaccination rates are in higher ranges for most states compared to the estimated vaccination rates in 2006. States vary widely in hepatitis B vaccination rates and in their compliance with the 2005 ACIP recommendation. There are many factors at various stages that might affect the successful implementation of the new ACIP recommendation as revealed in literature review. ^ Conclusions. HBV perinatal transmission can be eliminated, but it requires identifying the gaps and measures taken to increase the current vaccination coverage, ensuring timely administration of post exposure immunoprophylaxis and continued evaluations of the impact of immunization recommendations.^

Elimination of racial/ethnic Hepatitis B vaccination disparities in the US in the 2007--2008 National Health and Nutrition Examination Survey

Viral hepatitis is a significant public health problem worldwide and is due to viral infections that are classified as Hepatitis A, B, C, D, and E. Hepatitis B is one of the five known hepatic viruses. A safe and effective vaccine for Hepatitis B was first developed in 1981, and became adopted into national immunization programs targeting infants since 1990 and adolescents since 1995. In the U.S., this vaccination schedule has led to an 82% reduction in incidence from 8.5 cases per 100,000 in 1990 to 1.5 cases per 100,000 in 2007. Although there has been a decline in infection among adolescents, there is still a large burden of hepatitis B infection among adults and minorities. There is very little research in regards to vaccination gaps among adults. Using the National Health and Nutrition Examination Survey (NHANES) question "{Have you/Has SP (Study Participant)} ever received the 3-dose series of the hepatitis B vaccine?" the existence of racial/ethnic gaps using a cross-sectional study design was explored. In this study, other variables such as age, gender, socioeconomic variables (federal poverty line, educational attainment), and behavioral factors (sexual practices, self-report of men having sex with men, and intravenous drug use) were examined. We found that the current vaccination programs and policies for Hepatitis B had eliminated racial and ethnic disparities in Hepatitis B vaccination, but that a low coverage exists particularly for adults who engage in high risk behaviors. This study found a statistically significant 10% gap in Hepatitis B vaccination between those who have and those who do not have access to health insurance.^

Immune response to hepatitis B vaccination in drug using populations: A systematic review and meta-regression analysis

Hepatitis B virus (HBV) is a significant cause of liver diseases and related complications worldwide. Both injecting and non-injecting drug users are at increased risk of contracting HBV infection. Scientific evidence suggests that drug users have subnormal response to HBV vaccination and the seroprotection rates are lower than that in the general population; potentially due to vaccine factors, host factors, or both. The purpose of this systematic review is to examine the rates of seroprotection following HBV vaccination in drug using populations and to conduct a meta-analysis to identify the factors associated with varying seroprotection rates. Seroprotection is defined as developing an anti-HBs antibody level of ≥ 10 mIU/ml after receiving the HBV vaccine. Original research articles were searched using online databases and reference lists of shortlisted articles. HBV vaccine intervention studies reporting seroprotection rates in drug users and published in English language during or after 1989 were eligible. Out of 235 citations reviewed, 11 studies were included in this review. The reported seroprotection rates ranged from 54.5 – 97.1%. Combination vaccine (HAV and HBV) (Risk ratio 12.91, 95% CI 2.98-55.86, p = 0.003), measurement of anti-HBs with microparticle immunoassay (Risk ratio 3.46, 95% CI 1.11-10.81, p = 0.035) and anti-HBs antibody measurement at 2 months after the last HBV vaccine dose (RR 4.11, 95% CI 1.55-10.89, p = 0.009) were significantly associated with higher seroprotection rates. Although statistically nonsignificant, the variables mean age>30 years, higher prevalence of anti-HBc antibody and anti-HIV antibody in the sample population, and current drug use (not in drug rehabilitation treatment) were strongly associated with decreased seroprotection rates. Proportion of injecting drug users, vaccine dose and accelerated vaccine schedule were not predictors of heterogeneity across studies. Studies examined in this review were significantly heterogeneous (Q = 180.850, p = 0.000) and factors identified should be considered when comparing immune response across studies. The combination vaccine showed promising results; however, its effectiveness compared to standard HBV vaccine needs to be examined systematically. Immune response in DUs can possibly be improved by the use of bivalent vaccines, booster doses, and improving vaccine completion rates through integrated public programs and incentives.^

Influenza vaccination as a primary or secondary prevention for cardiovascular diseases: A systematic review of the literature

Background: Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. CVD mainly comprise of coronary heart disease and stroke and were ranked first and fourth respectively amongst leading causes of death in the United States. Influenza (flu) causes annual outbreaks and pandemics and is increasingly recognized as an important trigger for acute coronary syndromes and stroke. Influenza vaccination is an inexpensive and effective strategy for prevention of influenza related complications in high risk individuals. Though it is recommended for all CVD patients, Influenza vaccine is still used at suboptimal levels in these patients owing to prevailing controversy related to its effectiveness in preventing CVD. This review was undertaken to critically assess the effectiveness of influenza vaccination as a primary or secondary prevention method for CVD. ^ Methods: A systematic review was conducted using electronic databases OVID MEDLINE, PUBMED (National Library of Medicine), EMBASE, GOOGLE SCHOLAR and TRIP (Turning Research into Practice). The study search was limited to peer-reviewed articles published in English language from January 1970 through May 2012. The case control studies, cohort studies and randomized controlled trials related to influenza vaccination and CVD, with data on at least one of the outcomes were identified. In the review, only population-based epidemiologic studies in all ethnic groups and of either sex and with age limitation of 30 yrs or above, with clinical CVD outcomes of interest were included. ^ Results: Of the 16 studies (8 case control studies, 6 cohort studies and 2 randomized controlled trials) that met the inclusion criteria, 14 studies reported that there was a significant benefit in u influenza vaccination as primary or secondary prevention method for preventing new cardiovascular events. In contrary to the above findings, two studies mentioned that there was no significant benefit of vaccination in CVD prevention. ^ Conclusion: The available body of evidence in the review elucidates that vaccination against influenza is associated with reduction in the risk of new CVD events, hospitalization for coronary heart disease and stroke and as well as the risk of death. The study findings disclose that the influenza vaccination is very effective in CVD prevention and should be encouraged for the high risk population. However, larger and more future studies like randomized control trials are needed to further evaluate and confirm these findings. ^

Characterizing Overall Response to Two-shot Vaccination for BVDV Type 2 in Angus Weanling Calves

Vaccination is a management strategy utilized to help reduce prevalence of bovine respiratory disease in feedlots. However, not all animals respond similarly to vaccinations. It is believed that an animal’s genetics control part of the ability to respond to a vaccination protocol. In order to evaluate the genetic control of a new trait such as response to vaccination, it is important to understand the non-genetic factors that affect an animal’s response to vaccination. The objective of this study was to characterize the non-genetic factors affecting overall response to a two-shot vaccination for bovine viral diarrhea virus type 2 (BVDV2) in Angus weanling calves.

T cell vaccination induces T cell receptor Vβ-specific Qa-1-restricted regulatory CD8+ T cells

Vaccination of mice with activated autoantigen-reactive CD4+ T cells (T cell vaccination, TCV) has been shown to induce protection from the subsequent induction of a variety of experimental autoimmune diseases, including experimental allergic encephalomyelitis (EAE). Although the mechanisms involved in TCV-mediated protection are not completely known, there is some evidence that TCV induces CD8+ regulatory T cells that are specific for pathogenic CD4+ T cells. Previously, we demonstrated that, after superantigen administration in vivo, CD8+ T cells emerge that preferentially lyse and regulate activated autologous CD4+ T cells in a T cell receptor (TCR) Vβ-specific manner. This TCR Vβ-specific regulation is not observed in β2-microglobulin-deficient mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar Vβ8-specific Qa-1-restricted CD8+ T cells are also induced by TCV with activated CD4+ Vβ8+ T cells. These CD8+ T cells specifically lyse murine or human transfectants coexpressing Qa-1 and murine TCR Vβ8. Further, CD8+ T cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic protein-specific CD4+Vβ8+ T cell clone specifically recognize other CD4+ T cells and T cell tumors that express Vβ8 and the syngeneic Qa-1a but not the allogeneic Qa-1b molecule. Thus, Vβ-specific Qa-1-restricted CD8+ T cells are induced by activated CD4+ T cells. We suggest that these CD8+ T cells may function to specifically regulate activated CD4+ T cells during immune responses.

Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination

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.

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma

We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte–macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

Variable efficacy of repeated annual influenza vaccination

Conclusions have differed in studies that have compared vaccine efficacy in groups receiving influenza vaccine for the first time to efficacy in groups vaccinated more than once. For example, the Hoskins study [Hoskins, T. W., Davis, J. R., Smith, A. J., Miller, C. L. & Allchin, A. (1979) Lancet i, 33–35] concluded that repeat vaccination was not protective in the long term, whereas the Keitel study [Keitel, W. A., Cate, T. R., Couch, R. B., Huggins, L. L. & Hess, K. R. (1997) Vaccine 15, 1114–1122] concluded that repeat vaccination provided continual protection. We propose an explanation, the antigenic distance hypothesis, and test it by analyzing seven influenza outbreaks that occurred during the Hoskins and Keitel studies. The hypothesis is that variation in repeat vaccine efficacy is due to differences in antigenic distances among vaccine strains and between the vaccine strains and the epidemic strain in each outbreak. To test the hypothesis, antigenic distances were calculated from historical hemagglutination inhibition assay tables, and a computer model of the immune response was used to predict the vaccine efficacy of individuals given different vaccinations. The model accurately predicted the observed vaccine efficacies in repeat vaccinees relative to the efficacy in first-time vaccinees (correlation 0.87). Thus, the antigenic distance hypothesis offers a parsimonious explanation of the differences between and within the Hoskins and Keitel studies. These results have implications for the selection of influenza vaccine strains, and also for vaccination strategies for other antigenically variable pathogens that might require repeated vaccination.

Therapeutic passive vaccination against chronic Lyme disease in mice

Passive and active immunization against outer surface protein A (OspA) has been successful in protecting laboratory animals against subsequent infection with Borrelia burgdorferi. Antibodies (Abs) to OspA convey full protection, but only when they are present at the time of infection. Abs inactivate spirochetes within the tick and block their transmission to mammals, but do not affect established infection because of the loss of OspA in the vertebrate host. Our initial finding that the presence of high serum titers of anti-OspC Abs (5 to 10 μg/ml) correlates with spontaneous resolution of disease and infection in experimentally challenged immunocompetent mice suggested that therapeutic vaccination with OspC may be feasible. We now show that polyclonal and monospecific mouse immune sera to recombinant OspC, but not to OspA, of B. burgdorferi resolve chronic arthritis and carditis and clear disseminated spirochetes in experimentally infected C.B.-17 severe combined immunodeficient mice in a dose-dependent manner. This was verified by macroscopical and microscopical examination of affected tissues and recultivation of spirochetes from ear biopsies. Complete resolution of disease and infection was achieved, independent of whether OspC-specific immune sera (10 μg OspC-specific Abs) were repeatedly given (4× in 3- to 4-day intervals) before the onset (day 10 postinfection) or at the time of fully established arthritis and carditis (days 19 or 60 postinfection). The results indicate that in mice spirochetes constitutively express OspC and are readily susceptible to protective OspC-specific Abs throughout the infection. Thus, an OspC-based vaccine appears to be a candidate for therapy of Lyme disease.

Protective anti-tumor immunity induced by vaccination with recombinant adenoviruses encoding multiple tumor-associated cytotoxic T lymphocyte epitopes in a string-of-beads fashion

Vaccines harboring genes that encode functional oncoproteins are intrinsically hazardous, as their application may lead to introduction of these genes into normal cells and thereby to tumorigenesis. On the other hand, oncoproteins are especially attractive targets for immunotherapy of cancer, as their expression is generally required for tumor growth, making the arisal of tumor variants lacking these antigens unlikely. Using murine tumor models, we investigated the efficacy of polyepitope recombinant adenovirus (rAd) vaccines, which encode only the immunogenic T cell epitopes derived from several oncogenes, for the induction of protective anti-tumor immunity. We chose to employ rAd, as these are safe vectors that do not induce the side effects associated with, for example, vaccinia virus vaccines. A single polyepitope rAd was shown to give rise to presentation of both H-2 and human leukocyte antigen-restricted cytotoxic T lymphocyte (CTL) epitopes. Moreover, vaccination with a rAd encoding H-2-restricted CTL epitopes, derived from human adenovirus type 5 early region 1 and human papilloma virus type 16-induced tumors, elicited strong tumor-reactive CTL and protected the vaccinated animals against an otherwise lethal challenge with either of these tumors. The protection induced was superior compared with that obtained by vaccination with irradiated tumor cells. Thus, vaccination with polyepitope rAd is a powerful approach for the induction of protective anti-tumor immunity that allows simultaneous immunization against multiple tumor-associated T cell epitopes, restricted by various major histocompatibility complex haplotypes.

Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen

DNA vaccines that encode encephalitogenic sequences in tandem can protect from subsequent experimental autoimmune encephalomyelitis induced with the corresponding peptide. The mechanism for this protection and, in particular, if it is specific for the amino acid sequence encoding the vaccine are not known. We show here that a single amino acid exchange in position 79 from serine (nonself) to threonine (self) in myelin basic protein peptide MBP68–85, which is a major encephalitogenic determinant for Lewis rats, dramatically alters the protection. Moreover, vaccines encoding the encephalitogenic sequence MBP68–85 do not protect against the second encephalitogenic sequence MBP89–101 in Lewis rats and vice versa. Thus, protective immunity conferred by DNA vaccination exquisitely discriminates between peptide target autoantigens. No bystander suppression was observed. The exact underlying mechanisms remain elusive because no simple correlation between impact on ex vivo responses and protection against disease were noted.