http://www.mdpi.com/journal/vaccines Latest open access articles published in Vaccines at http://www.mdpi.com/journal/vaccines http://www.mdpi.com/2076-393X/1/2/167 Hepatitis B remains a significant health issue worldwide, and contributes significantly to the incidence of cirrhosis and hepatocellular carcinoma. Widespread adoption of hepatitis B vaccination strategies has lead to significant declines in acute hepatitis B infections. Current recommendations for vaccination in the non-pregnant population include vaccinating all persons found to have risk-factors for disease acquisition. Hepatitis B virus is known to occur through vertical transmission or early childhood transmission, and strategies to decrease transmission include avoidance of exposure, avoidance of high-risk behaviors, universal screening of women during pregnancy, and active and passive immunization. It is currently recommended that all pregnant women undergo screening for hepatitis B virus at presentation for prenatal care. Those who engage in high-risk behavior should be re-screened at presentation for delivery. Studies have demonstrated the safety and efficacy of the hepatitis B vaccine in pregnancy, and its use is an important component in prevention of disease acquisition. Pregnant women in the United States who are found to be at risk for disease acquisition should be specifically targeted for vaccination. Vaccines 2013-05-08 1 2 Review 10.3390/vaccines1020167 167 173 2076-393X 2013-05-08 doi: 10.3390/vaccines1020167 Robert Stewart Jeanne Sheffield http://www.mdpi.com/2076-393X/1/2/154 Rates of delay and refusal of recommended childhood vaccines are increasing in many U.S. communities. Children’s health care providers have a strong influence on parents’ knowledge, attitudes, and beliefs about vaccines. Provider attitudes towards immunizations vary and affect their immunization advocacy. One factor that may contribute to this variability is their familiarity with vaccine-preventable diseases and their sequelae. The purpose of this study was to investigate the association of health care provider year of graduation with vaccines and vaccine-preventable disease beliefs. We conducted a cross sectional survey in 2005 of primary care providers identified by parents of children whose children were fully vaccinated or exempt from one or more school immunization requirements. We examined the association of provider graduation cohort (5 years) with beliefs on immunization, disease susceptibility, disease severity, vaccine safety, and vaccine efficacy. Surveys were completed by 551 providers (84.3% response rate). More recent health care provider graduates had 15% decreased odds of believing vaccines are efficacious compared to graduates from a previous 5 year period; had lower odds of believing that many commonly used childhood vaccines were safe; and 3.7% of recent graduates believed that immunizations do more harm than good. Recent health care provider graduates have a perception of the risk-benefit balance of immunization, which differs from that of their older counterparts. This change has the potential to be reflected in their immunization advocacy and affect parental attitudes. Vaccines 2013-04-29 1 2 Article 10.3390/vaccines1020154 154 166 2076-393X 2013-04-29 doi: 10.3390/vaccines1020154 Michelle Mergler Saad Omer William Pan Ann Navar-Boggan Walter Orenstein Edgar Marcuse James Taylor M. deHart Terrell Carter Anthony Damico Neal Halsey Daniel Salmon http://www.mdpi.com/2076-393X/1/2/139 The Kaiser Permanente Vaccine Study Center is a specialized research organization in Oakland, California. They have been an active vaccine research group for many years, and have participated in and led a multitude of vaccine studies. This article will review the last three years of research activities. Vaccines 2013-04-25 1 2 Review 10.3390/vaccines1020139 139 153 2076-393X 2013-04-25 doi: 10.3390/vaccines1020139 Roger Baxter Nicola Klein http://www.mdpi.com/2076-393X/1/2/120 The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines. Vaccines 2013-04-16 1 2 Article 10.3390/vaccines1020120 120 138 2076-393X 2013-04-16 doi: 10.3390/vaccines1020120 Kamalakannan Velmurugan Leander Grode Rosemary Chang Megan Fitzpatrick Dominick Laddy David Hokey Steven Derrick Sheldon Morris David McCown Reginald Kidd Martin Gengenbacher Bernd Eisele Stefan Kaufmann John Fulkerson Michael Brennan http://www.mdpi.com/2076-393X/1/2/105 To examine changes in seroprevalence of antibodies to hepatitis A virus (HAV) during a period in which universal vaccine recommendations for all U.S. children were implemented, results from serologic testing from the National Health and Nutrition Examination Survey (NHANES) from 2003–2010 were analyzed among 7,989 participants age 6–19 years, born in the U.S. in two birth cohorts (1986–1996 and 1997–2004). Overall prevalence increased over time from 24.4% in 2003–2006 to the highest ever reported (37.6%) in 2007–2010. Specifically, increases reached statistical significance in the birth cohort born in the years after implementation of vaccine recommendations (1997–2004), among those of race/ethnicity other than white, non-Hispanic, and among states where recommendations were implemented later. The greatest increase over time was among the subgroup of persons in states with early implementation who were of race/ethnicity other than white, non-Hispanic. Geographic region and birth cohort based on vaccine recommendations as well as race/ethnicity were the main predictors of seropositivity in 2007–2010. The increase in Hepatitis A seroprevalence occurred during a time of decreasing incidence and increasing vaccination, however race/ethnic disparities persist. Vaccines 2013-04-10 1 2 Article 10.3390/vaccines1020105 105 119 2076-393X 2013-04-10 doi: 10.3390/vaccines1020105 Deanna Kruszon-Moran R. Klevens Geraldine McQuillan http://www.mdpi.com/2076-393X/1/2/88 An HIV vaccine, once it becomes available, could reduce vulnerability to HIV among African-American women. The purpose of this study was to assess determinants of HIV vaccine acceptability among African-American women across hypothetical levels of vaccine efficacy. Participants were recruited from a hospital-based family planning clinic in Atlanta, GA serving low-income patients (N = 321). Data were collected from audio-computer assisted surveys administered in the clinic waiting room. Psychosocial survey items were guided by Risk Homeostasis Theory (RHT) and Social Cognitive Theory (SCT). Multivariate logistic regression was used to identify determinants of acceptability for two hypothetical HIV vaccines with 50% and 90% efficacy. Overall, 63% of participants would accept a vaccine with 50% efficacy and 85% would accept a vaccine with 90% efficacy. In multivariate analyses, odds of acceptability for a vaccine with 50% efficacy were higher among participants with greater perceived HIV vaccine benefits (AOR = 1.13, p < 0.001) and lower among participants with more than high school education (AOR = 0.47, p = 0.033) and greater perceived costs of HIV vaccination (AOR = 0.95, p = 0.010). Odds of acceptability for a vaccine with 90% efficacy were higher among participants with greater perceived costs of unprotected sex (AOR = 1.08, p = 0.026), HIV vaccine benefits (AOR = 1.23, p < 0.001) and self-efficacy for sex refusal (AOR = 1.11, p = 0.044). HIV vaccine acceptability was high, particularly for a vaccine with 90% efficacy. Findings suggest that demographic and psychosocial factors may impact acceptability of an eventual HIV vaccine. Once an HIV vaccine is available, interventions to maximize uptake may benefit from using RHT and SCT constructs to target relevant psychosocial factors, such as perceived benefits and perceived costs of vaccination. Vaccines 2013-04-08 1 2 Article 10.3390/vaccines1020088 88 104 2076-393X 2013-04-08 doi: 10.3390/vaccines1020088 Julia Painter Clare Cene-Kush Alaina Conner Carrie Cwiak Lisa Haddad Mark Mulligan Ralph DiClemente http://www.mdpi.com/2076-393X/1/2/77 The Extended Parallel Process Model (EPPM) is an established threat- and efficacy-based behavioral framework for understanding health behaviors in the face of uncertain risk. A growing body of research has applied this model to understand these behaviors among the public health workforce. In this manuscript, we aim to explore the application of this framework to the public health workforce, with a novel focus on their confidence in vaccines and perceptions of vaccine injury compensation mechanisms. We characterize specific connections between EPPM’s threat and efficacy dimensions and relevant vaccine policy frameworks and highlight how these connections can usefully inform training interventions for public health workers to enhance their confidence in these vaccine policy measures. Vaccines 2013-04-08 1 2 Concept Paper 10.3390/vaccines1020077 77 87 2076-393X 2013-04-08 doi: 10.3390/vaccines1020077 Daniel Barnett Nicole Errett Lainie Rutkow http://www.mdpi.com/2076-393X/1/1/58 Part I. Basic Principles. TB vaccines cannot prevent establishment of the infection. They can only prevent an early pulmonary tubercle from developing into clinical disease. A more effective new vaccine should optimize both cell-mediated immunity (CMI) and delayed-type hypersensitivity (DTH) better than any existing vaccine. The rabbit is the only laboratory animal in which all aspects of the human disease can be reproduced: namely, the prevention of most primary tubercles, the arrestment of most primary tubercles, the formation of the tubercle’s solid caseous center, the liquefaction of this center, the formation of cavities and the bronchial spread of the disease. In liquefied caseum, virulent tubercle bacilli can multiply extracellularly, especially in the liquefied caseum next to the inner wall of a cavity where oxygen is plentiful. The bacilli in liquefied caseum cannot be reached by the increased number of activated macrophages produced by TB vaccines. Therefore, new TB vaccines will have little or no effect on the extracellular bacillary growth within liquefied caseum. TB vaccines can only increase the host’s ability to stop the development of new TB lesions that arise from the bronchial spread of tubercle bacilli from the cavity to other parts of the lung. Therefore, effective TB vaccines do not prevent the reactivation of latent TB. Such vaccines only control (or reduce) the number of metastatic lesions that result after the primary TB lesion was reactivated by the liquefaction process. (Note: the large number of tubercle bacilli growing extracellularly in liquefied caseum gives rise to mutations that enable antimicrobial resistance—which is a major reason why TB still exists today). Part II. Preclinical Testing. The counting of grossly visible tubercles in the lungs of rabbits after the inhalation of virulent human-type tubercle bacilli is the most pertinent preclinical method to assess the efficacy of new TB vaccines (because an effective vaccine will stop the growth of developing tubercles before while they are still microscopic in size). Unfortunately, rabbits are rarely used in preclinical vaccine trials, despite their relative ease of handling and human-like response to this infection. Mice do not generate an effective DTH response, and guinea pigs do not generate an effective CMI response. Only the rabbits and most humans can establish the proper amount of DTH and CMI that is necessary to contain this infection. Therefore, rabbits should be included in all pre-clinical testing of new TB vaccines. New drugs (and/or immunological procedures) to reduce liquefaction and cavity formation are urgently needed. A simple intradermal way to select such drugs or procedures is described herein. Part III. Clinical Testing. Vaccine trials would be much more precise if the variations in human populations (listed herein) were taken into consideration. BCG and successful new TB vaccines should always increase host resistance to TB in naive subjects. This is a basic immunological principle. The efficacies of new and old TB vaccines are often not recognized, because these variations were not identified in the populations evaluated. Vaccines 2013-01-25 1 1 Concept Paper 10.3390/vaccines1010058 58 76 2076-393X 2013-01-25 doi: 10.3390/vaccines1010058 Arthur Dannenberg Bappaditya Dey http://www.mdpi.com/2076-393X/1/1/34 Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness. Vaccines 2013-01-11 1 1 Article 10.3390/vaccines1010034 34 57 2076-393X 2013-01-11 doi: 10.3390/vaccines1010034 Carolyn Shoen Michelle DeStefano Cynthia Hager Kyi-Toe Tham Miriam Braunstein Alexandria Allen Hiriam Gates Michael Cynamon Douglas Kernodle http://www.mdpi.com/2076-393X/1/1/17 Although mentioned in the UK pandemic plan, essential service providers were not among the priority groups. They may be important targets of future influenza pandemic vaccination campaigns. Therefore, we conducted a cross-sectional survey among 380 employees from West Midlands police headquarters and 15 operational command units in the West Midlands Area during December 2009–February 2010 to identify factors affecting intention to accept the pandemic influenza A (H1N1) vaccine. One hundred and ninety nine (52.4%) employees completed the questionnaire. 39.7% were willing to accept the vaccine. The most common reasons for intention to accept were worry about catching Swine Flu (n = 42, 53.2%) and about infecting others (n = 40, 50.6%). The most common reason for declination was worry about side effects (n = 45, 57.0%). The most important factor predicting vaccine uptake was previous receipt of seasonal vaccine (OR 7.9 (95% CI 3.4, 18.5)). Employees aged <40 years, males, current smokers, and those who perceived a greater threat and severity of swine flu were also more likely to agree to the vaccine. The findings of this study could be used to improve future pandemic immunization strategies. Targeted education programs should be used to address misconceptions; the single most important factor which might lead to a large improvement in uptake is to allay concern about side effects. Vaccines 2012-12-20 1 1 Article 10.3390/vaccines1010017 17 33 2076-393X 2012-12-20 doi: 10.3390/vaccines1010017 Alice Beattie Katie Palmer Emily Rees Zoe Riddell Charlotte Roberts Rachel Jordan http://www.mdpi.com/2076-393X/1/1/1 Colorectal cancer is the third most common cause of cancer-related deaths and the second most prevalent (after breast cancer) in the western world. High metastatic relapse rates and severe side effects associated with the adjuvant treatment have urged oncologists and clinicians to find a novel, less toxic therapeutic strategy. Considering the limited success of the past clinical trials involving peptide vaccine therapy to treat colorectal cancer, it is necessary to revise our knowledge of the immune system and its potential use in tackling cancer. This review presents the efforts of the scientific community in the development of peptide vaccine therapy for colorectal cancer. We review recent clinical trials and the strategies for immunologic monitoring of responses to peptide vaccine therapy. We also discuss the mechanisms underlying the therapy and potential molecular targets in colon cancer. Vaccines 2012-08-24 1 1 Review 10.3390/vaccines1010001 1 16 2076-393X 2012-08-24 doi: 10.3390/vaccines1010001 Aleksandra Bartnik Ajit Johnson Nirmal Shi-Yu Yang