Prime-boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu+ metastatic breast cancer in mice.

INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu+ cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models. METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines. RESULTS: Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime-boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime-boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNgamma. CONCLUSION: We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime-boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime-boost protocol, is justified.

Prime and boost vaccination against HER2/neu in breast cancer

Breast cancer is the most common cancer among women with approximately 180,000 new cases being diagnosed yearly in the United States (1). HER2/neu gene amplification and subsequent protein overexpression is found in 20–30% of breast cancer patients and can lead to the promotion of various metastasis-related properties (2–4) and/or resistance to cancer therapies such as chemotherapy and radiation (5). ^ The protein product of the HER2/neu gene, p185, is a proven target for immunological therapy. Recently, passive immunotherapy with the monoclonal antibody Trastuzumab® has validated an immunological approach to HER2/neu+ breast cancer. Immunity to HER2/ neu, when found in breast cancer patients, is of low magnitude. Vaccination-induced HER2/neu-specific antibodies and HER2/neu-specific cytotoxic T cells could result in long-lived immunity with therapeutic benefit. Many features of DNA vaccines and attenuated viral vectors may contribute to the efficacy of prime-boost vaccination. In particular, vaccines capable of eliciting strong cell-mediated immunity are thought to hold the greatest promise for control of cancer (6–9). ^ To optimize cellular immunization to HER2/neu in my study, the HER2/neu gene was presented to the immune system using a priming vector followed by a second vector used as the boost. In both animals and humans, priming with DNA and boosting with a poxviruses, vaccinia or canarypox appears to be particularly promising for induction of a broad immune responses (10). ^ I tested three gene vaccines encoding the HER2/neu gene: (1) a plasmid, SINCP, that contains part of the genome of Sindbis virus; (2) Viral Replicon Particles (VRP) of Venezuela Equine Encephalitis virus (VEE) and (3) E1/E2a-deleted human Type 5 Adenovirus. In SINCP and the VRP, the caspid and envelope genes of the virus were deleted and replaced with the gene for HER2/neu. SINCP-neu, VRP- neu and Adeno-neu when used alone were effective vaccines protecting healthy mice from challenge with a breast cancer cell line injected in the mammary fat pad or injected i.v. to induce experimental lung metastasis. However, SINCP-neu, VRP-neu or Adeno-neu when used alone were not able to prolong survival of mice in therapeutic models in which vaccination occurred after injection of a breast cancer cell line. ^ When the vaccines were combined in a mixed regimen of a SINCP- neu prime VRP-neu or Adeno-neu boost, there was a significant difference in tumor growth and survival in the therapeutic vaccine models. In vitro assays demonstrated that vaccination with each of the three vaccines induced IgG specific for p185, the gene product of HER2/neu, induced p185-specific T lymphocytes, as measured by tetramer analysis. Vaccination also induced intracellular INF-γ and a positive ELISPOT assay. These findings indicate that SINCP-neu, VRP-neu and Adeno-neu, used alone or in combination, may have clinical potential as adjuvant immunotherapy for the treatment of HER2/neu-expressing tumors. ^

DNA vaccination against the novel tumor antigen, MUC18, for the therapy of metastatic melanoma

Melanoma patients with metastases have a very low survival rate and limited treatment options. Therefore, the targeting of melanoma cells when they begin to invade and metastasize would be beneficial. A specific adhesion molecule that is upregulated at the vertical growth phase is the melanoma cell adhesion molecule (MCAM/MUC18). MUC18 is expressed in late primary and metastatic melanoma with little or no expression on normal melanocytes. MUC18 has been demonstrated to have a role in the progression and metastasis of human melanoma. We utilized the alphavirus-based DNA plasmid, SINCp, encoding full length human MUC18 for vaccination against B16F10 murine melanoma cells expressing human MUC18. The alphavirus-based DNA plasmid leads to the expression of large quantities of heterologous protein as well as danger signals due to dsRNA intermediates produced during viral replication. In a preventative primary tumor model and an experimental tumor model, mice vaccinated against human MUC18 had decreased tumor incidence and reduced lung metastases when challenged with B16F10 murine melanoma cells expressing human MUC18. In a therapeutic tumor model, vaccination against human MUC18 reduced the tumor burden in mice with pre-existing lung metastases but did not have a significant effect on therapeutic vaccination in a primary tumor model. We next cloned murine MUC18 into SINCp for use in determining the efficacy of vaccination against murine MUC18 in a syngeneic animal model. Mice were vaccinated and challenged in a primary tumor and experimental metastasis model. In both models, vaccination significantly reduced tumor incidence and lung metastases. Humoral and cell-mediated responses were then determined. Flow cytometry and immunohistochemistry showed that specific antibodies were developed from vaccination against both human and murine MUC18. IgG2a antibody isotype was also developed indicating a Th1 type response. ELISPOT results showed that mice vaccinated against human MUC18 created a specific T cell response to targets expressing human MUC18. Mice vaccinated against murine MUC18 raised specific effector cells against target cells expressing murine MUC18 in a cell killing assay. These results indicate that vaccination against MUC18 developed specific immune responses against MUC18 and were effective in controlling tumor growth in melanoma expressing MUC18. ^

Survey of VFC provider knowledge of catch-up regimens and contraindications to vaccination in Houston, Texas

In 2004, Houston had one of the lowest childhood immunization levels among major metropolitan cities in the United States at 65% for the 4:3:1:3:3 vaccination series. Delays in the receipt of scheduled vaccinations may be related to missed opportunities due to health care provider lack of knowledge about catch-up regimens and contraindications for pediatric vaccination. The objectives of this study are to identify, measure, and report on VFC provider-practice characteristics, knowledge of catch-up regimens and contraindications, and use of Reminder recall (R/R) and moved or gone elsewhere (MOGE) practices among providers with high (>80%) and low (<70%) immunization coverage among 19-35 month old children. The sampling frame consists of 187 Vaccines for Children (VFC) providers with 2004 clinic assessment software application (CASA) scores. Data were collected by personal interview with each participating practice provider. Only ten VFC providers were successful at maximizing vaccinations for every vignette and no provider administered the maximum possible number of vaccinations at visit 2 for all six vignettes. Both coverage groups administered polio conjugate vaccine (PCV), haemophilus influenza type b (Hib), and diphtheria, tetanus and acellular pertussis (DTaP) most frequently and omitted most frequently varicella zoster vaccine (VZV) and measles, mumps, and rubella (MMR) vaccine. ^

Influenza vaccination and peoples' knowledge and attitudes towards it: Factors that influenced influenza vaccination during the 2004--2005 influenza vaccine shortage

Influenza and pneumonia together comprise the seventh leading cause of death among adults in the U.S and were responsible for 65,163 deaths in 2003 and an average of 36,000 deaths per year in the United States from 1990 to 1999. Vaccination is efficacious and cost-effective in terms of preventing the infection and reducing both health care costs and productivity losses associated with influenza illness. The vaccine shortage of 2004–2005 resulted in a 39% decrease in the influenza vaccine supplies. During the fall of 2004, we conducted a nationwide, random-digit dialing, telephonic-interview survey of 1,202 adults aged 18 years and older to ascertain influenza vaccine knowledge, attitude and behavior. Of the 1,202 total interviewed subjects, 44.7% had received or intended to receive vaccine at the time of the survey (2004–05) and 39.6% had received the influenza vaccine the previous year (2003–04). Receipt of vaccine increased with previous receipt of the influenza vaccine (OR 13.17, 95% CI 8.65–20.08), increased motivation status (OR 7.58, 95% CI 4.03–14.25), subjective risk status (OR 3.33, 95% CI 2.23–4.97), age (OR 1.83, 95% CI 1.22–2.75) and previous receipt of the pneumococcal vaccine (OR 1.75, 95% CI 1.02–3.0). The influenza vaccine shortage of 2004–05 did not have a negative impact on the vaccination rates of study population. In addition to the increased rates, a large majority of respondents were also aware of the shortage of influenza vaccine during the 2004–05 season, about the indications for receiving the influenza vaccine, about alternative methods to prevent contracting the influenza and increased motivation to receive the vaccine. ^

Hepatitis B vaccination of high risk pregnant women: A clinical trial at Parkland Memorial Hospital

Hepatitis B infection is a major public health problem of global proportions. It is estimated that 2 billion people worldwide are infected by the Hepatitis B virus (HBV) at some point, and 350 million are chronic carriers. The Centers for Disease Control and Prevention (CDC) report an incidence in the United States of 140,000–320,000 infections each year (asymptomatic and symptomatic), and estimate 1–1.25 million people are chronically infected. Hepatitis B and its chronic complications (cirrhosis of the liver, liver failure, hepatocellular carcinoma) responsible for 4,000–5,000 deaths in America each year. ^ One quarter of those who become chronic carriers develop progressive liver disease, and chronic HBV infection is thought to be responsible for 60 million cases of cirrhosis worldwide, surpassing alcohol as a cause of liver disease. Since there are few treatment options for the person chronically infected with Hepatitis B, and what is available is expensive, prevention is clearly best strategy for combating this disease. ^ Since the approval of the Hepatitis B vaccine in 1981, national and international vaccination campaigns have been undertaken for the prevention of Hepatitis B. Despite encouraging results, however, studies indicate that prevalence rates of Hepatitis B infection have not been significantly reduced in certain high risk populations because vaccination campaigns targeting those groups do not exist and opportunities for vaccination by individual physicians in clinical settings are often missed. Many of the high-risk individuals who go unvaccinated are women of childbearing age, and a significant proportion of these women become infected with the Hepatitis B virus (HBV) during pregnancy. Though these women are often seen annually or for prenatal care (because of the close spacing of their children and their high rate of fertility), the Hepatitis B vaccine series is seldom recommended by their health care provider. In 1993, ACOG issued a statement recommending Hepatitis B vaccination of pregnant women who were defined as high-risk by diagnosis of a sexually transmitted disease. ^ Hepatitis B vaccine has been extensively studied in the non-pregnant population. The overall efficacy of the vaccine in infants, children and adults is greater than 90%. In the small clinical trials to date, the vaccine seemed to be effective in those pregnant women receiving 3 doses; however, by using the usual 0, 1 and 6 month regimen, most pregnant women were unable to complete a full series during pregnancy. There is data now available supporting the use of an "accelerated" dosing schedule at 0, 1 and 4 months. This has not been evaluated in pregnant women. A clinical trial proving the efficacy of the 0, 1, 4 schedule and its feasibility in this population would add significantly to the body of research in this area, and would have implications for public health policy. Such a trial was undertaken in the Parkland Memorial Hospital Obstetrical Infectious Diseases clinic. In this study, the vaccine was very well tolerated with no major adverse events reported, 90% of fully vaccinated patients achieved immunity, and only Body Mass Index (BMI) was found to be a significant factor affecting efficacy. This thesis will report the results of the trial and compare it to previous trials, and will discuss barriers to implementation, lessons learned and implications for future trials. ^

Associations between vaccination and childhood cancers in Texas counties

Background. In Dr. Mel Greaves "delayed-infection hypothesis," postponed exposure to common infections increases the likelihood of childhood cancer. Hygienic advancements in developed countries have reduced children's exposure to pathogens and children encounter common infectious agents at an older age with an immune system unable to deal with the foreign antigens. Vaccinations may be considered to be simulated infections as they prompt an antigenic response by the immune system. Vaccinations may regulate the risk of childhood cancer by modulating the immune system. The aim of the study was to determine if children born in Texas counties with higher levels of vaccination coverage were at a reduced risk for childhood cancer.^ Methods. We conducted a case-control study to examine the risk of childhood cancers, specifically leukemia, brain tumors, and non-Hodgkin lymphoma, in relation to vaccination rates in Texas counties. We utilized a multilevel mixed-effects regression model of the individual data from the Texas Cancer Registry (TCR) with group-level exposure data (i.e., the county- and public health region-level vaccination rates).^ Results. Utilizing county-level vaccination rates and controlling for child's sex, birth year, ethnicity, birth weight, and mother's age at child's birth the hepatitis B vaccine revealed negative associations with developing all cancer types (OR = 0.81, 95% CI: 0.67–0.98) and acute lymphoblastic leukemia (ALL) (OR = 0.63, 95% CI: 0.46–0.88). The decreased risk for ALL was also evident for the inactivated polio vaccine (IPV) (OR = 0.67, 95% CI: 0.49–0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44-0.87). Using public health region vaccine coverage levels, an inverse association between the Haemophilus influenzae type b (Hib) vaccine and ALL (OR: 0.58; 95% CI: 0.42–0.82) was present. Conversely, the measles, mumps, and rubella (MMR) vaccine resulted in a positive association with developing non-Hodgkin lymphoma (OR = 2.81, 95% CI: 1.27–6.22). ^

Impact of maternal Tdap vaccination on pertussis infection in young infants

Undiagnosed infected mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention (CDC) recommends Tdap vaccine for post-partum women before hospital discharge. This intervention has been implemented at Ben Taub General Hospital (BTGH) in Houston, TX since January 2008. Our objective was to compare the proportion of infants born at BTGH and developing pertussis to the total number of pertussis cases before and after the intervention. Methods. We conducted a cross-sectional comparative study between the pre-intervention (7/2000 to 12/2007) and post-intervention (1/2008 to 5/2009) periods. Information on pertussis diagnosis was determined using ICD-9 codes, infection control records, and molecular microbiology reports from Texas Children's Hospital (TCH) and BTGH. Only patients ≤ 6 months of age with laboratory-confirmed B. pertussis infection were included in the study. Results. 481 infants had pertussis illness; 353 (73.3%) during pre-intervention and 128 (26.6%) during post-intervention years. The groups were comparable in all measures including age (median 73 vs. 62.5 days; p=0.08), gender (males 54.2%; p=0.47), length of hospitalization (median 9.8 vs. 4 9.5 days; p=0.5), outcomes (2 deaths in each period; p=0.28) and pertussis illness at TCH (95.2% vs. 95.3%; p=0.9). The proportion of pertussis patients born at BTGH, and thus amenable to protection by the intervention, was not statically different between the two periods after adjusting for age, gender and ethnicity (7.3% vs. 9.3%; an OR=1.05, 95% CI 0.5-2.1, p=0.88). Conclusions. Vaccinating only mothers with Tdap in the post-partum period does not reduce the proportion of pertussis in infants age ≤ 6 months. Efforts should be directed at Tdap immunization of not only mothers, but also all household and key contacts of newborns to protect them against pertussis illness before the primary DTaP series is completed.^

A review of economic analysis in the vaccination program; decision making and governance: Adivisory Committee on Immunization Practices (ACIP)

The Advisory Committee on Immunization Practices (ACIP) develops written recommendations for the routine administration of vaccines to children and adults in the U.S. civilian population. The ACIP is the only entity in the federal government that makes such recommendations. ACIP elaborates on selection of its members and rules out concerns regarding its integrity, but fails to provide information about the importance of economic analysis in vaccine selection. ACIP recommendations can have large health and economic consequences. Emphasis on economic evaluation in health is a likely response to severe pressures of the federal and state health budget. This study describes the economic aspects considered by the ACIP while sanctioning a vaccine, and reviews the economic evaluations (our economic data) provided for vaccine deliberations. A five year study period from 2004 to 2009 is adopted. Publicly available data from ACIP web database is used. Drummond et al. (2005) checklist serves as a guide to assess the quality of economic evaluations presented. Drummond et al.'s checklist is a comprehensive hence it is unrealistic to expect every ACIP deliberation to meet all of their criteria. For practical purposes we have selected seven criteria that we judge to be significant criteria provided by Drummond et al. Twenty-four data points were obtained in a five year period. Our results show that out of the total twenty-four data point‘s (economic evaluations) only five data points received a score of six; that is six items on the list of seven were met. None of the data points received a perfect score of seven. Seven of the twenty-four data points received a score of five. A minimum of a two score was received by only one of the economic analyses. The type of economic evaluation along with the model criteria and ICER/QALY criteria met at 0.875 (87.5%). These three criteria were met at the highest rate among the seven criteria studied. Our study findings demonstrate that the perspective criteria met at 0.583 (58.3%) followed by source and sensitivity analysis criteria both tied at 0.541 (54.1%). The discount factor was met at 0.250 (25.0%).^ Economic analysis is not a novel concept to the ACIP. It has been practiced and presented at these meetings on a regular basis for more than five years. ACIP‘s stated goal is to utilize good quality epidemiologic, clinical and economic analyses to help policy makers choose among alternatives presented and thus achieve a better informed decision. As seen in our study the economic analyses over the years are inconsistent. The large variability coupled with lack of a standardized format may compromise the utility of the economic information for decision-making. While making recommendations, the ACIP takes into account all available information about a vaccine. Thus it is vital that standardized high quality economic information is provided at the ACIP meetings. Our study may provide a call for the ACIP to further investigate deficiencies within the system and thereby to improve economic evaluation data presented. ^

Studies of biological rhythms in responses to influenza infection and vaccination

Three studies examined seasonal or circadian variations in selected responses to influenza infection or vaccination. The first, a seroepidemiologic study, evaluated temporal patterns of antibody titers to influenza A/Texas. Human umbilical cord bloods were sampled over a two-year period when the virus was not present in the community. No endogenous seasonal pattern was detected. The second study included three experiments on circadian rhythms in mice. Neither susceptibility nor protection from inactivated or attenuated vaccine varied significantly according to time of administration. A slight effect, however, was suggested with inactivated vaccine. Three human vaccine trials comprised the third study. Outcome variables included rise in antibody titer, final antibody titer, incidence of adverse reactions, and protection from community infection. Patterns in antibody response and protection variables were inconsistent, and generally not clinically significant. Local reactions to inactivated vaccine were more frequent if injections were received in the afternoon as compared to morning. This was true to adults that had been previously vaccinated. ^

Process and outcome evaluation of the hepatitis B perinatal vaccination program in Houston, Texas, 1991--1993

A retrospective cohort study was designed to evaluate the compliance of vaccination dose schedules and vaccination effectiveness at 12 months of age among a total of 226 high-risk infants born to HBsAg-positive pregnant women who participated in the HBV Perinatal Vaccination Program in Houston, Texas, 1991-1993.^ The seroprevalence of HBsAg-positivity was 0.5% among pregnant women who attended prenatal clinics in Houston, Texas, 1991-1993. The Asian women had the highest seroprevalence rate (5.9%), followed by black (1.9%), white (0.7%), and Hispanic women (0.3%). The seroprevalence of HBsAg increased with age (p =.02); the highest seroprevalence rate found among the $>$40 group (5.4%), followed by the 20-40 age group, and the $<$20 age. A steady increase was observed in the number of infants, from 45 in 1991, to 103 in 1993. The majority of these infants were black (58.0%), followed by Hispanic (28.8%), Asian (8.4%), and white infants (4.0%). Significant increases were observed from 1991 to 1993 in the number of infants who initiated vaccination (86.7% to 98.1%, p =.02) and in those infants who were post-tested at 12 months of age (24.4% to 44.7%, p =.04). During the same period an increase was also observed in the number of infants who completed the vaccination dose schedules (62.2% to 72.8%, p =.37). The compliance rates were not statistically significant regarding gender, race or ethnicity, health service area, medical referral source, and residential geographic areas. About 56.0% of the reasons cited for non-compliance among the 144 infants who neither completed the vaccination dose schedules nor received the 12-month post-test were "moved," and "no response/not at home." A total of 82 infants completed the vaccination dose schedules and were post-tested at 12 months of age for anti-HBs-positivity, and 96.3% of these infants seroconverted. A race-specific statistically significant seroconversion difference was found among infants who received all vaccination doses and were post-tested at 12 months of age (100% for the black and the white, 96.3% for the Hispanic, and 80.0% for the Asians infants, p =.05).^ From a public health perspective, the HBV Perinatal Vaccination Program improved during its first three years (1991-1993). It was effective in preventing perinatal HBV infection in almost 97.0% of infants who were vaccinated and post-tested. To increase the efficiency and efficacy of the program, the following recommendations are proposed: (1) Increase the vaccination compliance rate by educating and improving the tracking, communication and coordination channels with those individuals involved in the process and by increasing staff resources. (2) Reduce the post-test vaccination non-compliance by post-testing infants simultaneously with third vaccination dose at 6 months of age, and only post-test those infants who are anti-HBs-negative at 9-12 months of age. (Abstract shortened by UMI.) ^

Use of intranet and other interventions to increase influenza vaccination among health care workers

Influenza (the flu) is a serious respiratory illness that can cause severe complications, often leading to hospitalization and even death. Influenza epidemics occur in most countries every year, usually during the winter months. Despite recommendations from the Centers for Disease Control and Prevention (CDC) and efforts by health care institutions across the United States, influenza vaccination rates among health care workers in the United States remain low. How to increase the number of vaccinated health care workers is an important public health question and is examined in two journal articles included here. ^ The first journal article evaluates the effectiveness of an Intranet intervention in increasing the proportion of health care workers (HCWs) who received influenza vaccination. Hospital employees were required go to the hospital's Intranet and select "vaccine received," "contraindicated," or "declined" from the online questionnaire. Declining employees automatically received an online pop-up window with education about vaccination; managers were provided feedback on employees' participation rates via e-mail messages. Employees were reminded of the Intranet requirement in articles in the employee newsletter and on the hospital's Intranet. Reminders about the Intranet questionnaire were provided through managers and newsletters to the HCWs. Fewer than half the employees (43.7%) completed the online questionnaire. Yet the hospital witnessed a statistically significant increase in the percentage of employees who received the flu vaccine at the hospital – 48.5% in the 2008-09 season as compared to 36.5%, 38.5% and 29.8% in the previous three years (P < 0.05). ^ The second article assesses current interventions employed by hospitals, health systems and nursing homes to determine which policies have been the most effective in boosting vaccination rates among American health care workers. A systematic review of research published between January 1994 and March 2010 suggests that education is necessary but not usually sufficient to increase vaccine uptake. Education about the flu and flu vaccines is most effective when complemented with easy access and making the vaccine free, although this combination may not be sufficient to achieve the desired vaccination levels among HCWs. The findings point toward adding incentives for HCWs to get vaccinated and requiring them to record their vaccination status on a declination/consent form – either written or electronic. ^ Based on these findings, American health care organizations, such as hospitals, nursing homes, and long-term care facilities, should consider using online declination forms as a method for increasing influenza vaccination rates among their employees. These online forms should be used in conjunction with other policies, including free vaccine, mobile distribution and incentives. ^ To further spur health care organizations to adopt policies and practices that will raise influenza vaccination rates among employees, The Joint Commission – an independent, not-for- profit organization that accredits and certifies more than 17,000 health care organizations and programs in the United States – should consider altering its standards. Currently, The Joint Commission does not require signed declination forms from employees who eschew vaccination; it only echoes the CDC's recommendations: "Health care facilities should require personnel who refuse vaccination to complete a declination form." Because participation in Joint Commission accreditation is required for Medicare reimbursement, action taken by the Joint Commission to require interventions such as mandatory declination/consent forms might result in immediate action by health care organizations to follow these new standards and lead to higher vaccination rates among HCWs.^ 1“Frequently Asked Questions for H1N1 and Seasonal Influenza.” The Joint Commission - Infection Control: http://www.jointcommission.org/PatientSafety/InfectionControl/h1n1_faq.htm. ^

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.^