Vaccines, Volume 2, Issue 1 (March 2014) – 12 articles , Pages 1-195

The attenuated live M. bovis Bacille-Calmette-Guérin (BCG) is still the sole vaccine used against tuberculosis, but confers only variable efficacy against adult pulmonary tuberculosis (TB). Though no clear explanation for this limited efficacy has been given, different hypotheses have been advanced, such as the waning of memory T-cell responses, a reduced antigenic repertoire and the inability to induce effective CD8⁺ T-cell responses, which are known to be essential for latent tuberculosis control. In this study, a new BCG-based vaccination protocol was studied, in which BCG was formulated in combination with a plasmid DNA vaccine. As BCG is routinely administered to neonates, we have evaluated a more realistic approach of a simultaneous intradermal coadministration of BCG with pDNA encoding the prototype antigen, PPE44. Strongly increased T- and B-cell responses were observed with this protocol in C57BL/6 mice when compared to the administration of only BCG or in combination with an empty pDNA vector, as measured by Th1-type spleen cell cytokine secretion, specific IgG antibodies, as well as specific IFN-γ producing/cytolytic-CD8⁺ T-cells. Moreover, we observed a bystander activation induced by the coding plasmid, resulting in increased immune responses against other non-plasmid encoded, but BCG-expressed, antigens. In all, these results provide a proof of concept for a new TB vaccine, based on a BCG-plasmid DNA combination. Full article

Since the initial proof-of-concept studies examining the ability of antigen-encoded plasmid DNA to serve as an immunogen, DNA vaccines have evolved as a clinically safe and effective platform for priming HIV-specific cellular and humoral responses in heterologous “prime-boost” vaccination regimens. Direct injection of plasmid DNA into the muscle induces T- and B-cell responses against foreign antigens. However, the insufficient magnitude of this response has led to the development of approaches for enhancing the immunogenicity of DNA vaccines. The last two decades have seen significant progress in the DNA-based vaccine platform with optimized plasmid constructs, improved delivery methods, such as electroporation, the use of molecular adjuvants and novel strategies combining DNA with viral vectors and subunit proteins. These innovations are paving the way for the clinical application of DNA-based HIV vaccines. Here, we review preclinical studies on the DNA-prime/modified vaccinia Ankara (MVA)-boost vaccine modality for HIV. There is a great deal of interest in enhancing the immunogenicity of DNA by engineering DNA vaccines to co-express immune modulatory adjuvants. Some of these adjuvants have demonstrated encouraging results in preclinical and clinical studies, and these data will be examined, as well. Full article

DNA vaccination has been studied in the last 20 years for HIV vaccine research. Significant experience has been accumulated in vector design, antigen optimization, delivery approaches and the use of DNA immunization as part of a prime-boost HIV vaccination strategy. Key historical data and future outlook are presented. With better understanding on the potential of DNA immunization and recent progress in HIV vaccine research, it is anticipated that DNA immunization will play a more significant role in the future of HIV vaccine development. Full article

The current study examined and compared the willingness of young Black men who have sex with men (YBMSM) to accept pre-exposure prophylaxis (PrEP), adult male circumcision, and condoms for reducing their risk of HIV acquisition. The majority (67%) reported unprotected receptive anal sex in the last six months. About three-quarters (71%) would accept using PrEP if it was 100% effective. Cost influenced PrEP acceptance with 19% indicating acceptance at $100 per month co-pay. Of those not circumcised, 50% indicated willingness if circumcision was 100% effective. Acceptance of circumcision decreased markedly to 17% with co-pays of $100. About 73% of men were willing to use condoms if they were 100% effective and 50% indicated a willingness at the cost of $10 per month. The findings suggest that condom use promotion strategies should remain at the forefront of public health efforts to control HIV incidence among YBMSM. Full article

Seven-valent pneumococcal conjugate vaccine (PCV7) introduction and routine pediatric use has substantially reduced the burden of Streptococcus pneumoniae disease worldwide. However, a significant amount of disease burden, due to serotypes not contained in PCV7, still exists globally. A newly recognized serotype, 6C, was until recently, identified and reported as serotype 6A. This review summarizes the serotype epidemiology of pneumococcal disease pre- and post-introduction of PCV7, available post-marketing surveillance data following the introduction of higher valency pneumococcal vaccines (PCV10, PCV13) and future prospects for the development of new pneumococcal vaccines. Full article

In late October 2011, the Monroe County Department of Public Health (MCDPH) was notified of a suspected case of meningitis in a 9-year old girl from Monroe County, NY. Laboratory testing at the New York State Department of Health (NYSDOH) Wadsworth Center confirmed the identification of Haemophilus influenzae serotype e (Hie) isolated from the patient’s cerebrospinal fluid (CSF) using real-time polymerase chain reaction (RT-PCR). The universal immunization of infants with conjugate H. influenzae type b (Hib) vaccine has significantly reduced the incidence of invasive Hib disease, including meningitis, one of the most serious complications for infected children. Not surprisingly, as the epidemiology of invasive H. influenzae continues to change, non-Hib serotypes will likely become more common. The findings reported here underscore the importance for clinicians, public health officials, and laboratory staff to consider non-Hib pathogens in pediatric cases of meningitis, especially when initial investigations are inconclusive. Full article

The advantages of genetic immunization of the new vaccine using plasmid DNAs are multifold. For example, it is easy to generate plasmid DNAs, increase their dose during the manufacturing process, and sterilize them. Furthermore, they can be stored for a long period of time upon stabilization, and their protein encoding sequences can be easily modified by employing various DNA-manipulation techniques. Although DNA vaccinations strongly increase Th1-mediated immune responses in animals, several problems persist. One is about their weak immunogenicity in humans. To overcome this problem, various genetic adjuvants, electroporation, and prime-boost methods have been developed preclinically, which are reviewed here. Full article

Streptococcus pneumoniae still causes severe morbidity and mortality worldwide, especially in young children and the elderly. Much effort has been dedicated to developing protein-based universal vaccines to conquer the current shortcomings of capsular vaccines and capsular conjugate vaccines, such as serotype replacement, limited coverage and high costs. A recombinant live vector vaccine delivering protective antigens is a promising way to achieve this goal. In this review, we discuss the researches using live recombinant vaccines, mainly live attenuated Salmonella and lactic acid bacteria, to deliver pneumococcal antigens. We also discuss both the limitations and the future of these vaccines. Full article

Recent studies indicate that DNA immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. However, there is limited information on the mechanism of this effect. In particular, it is not known whether DNA immunization can also enhance the development of antigen-specific B cell development. In this report, a pilot study was conducted using plague LcrV immunogen as a model system to determine whether DNA immunization is able to enhance LcrV-specific B cell development in mice. Plague is an acute and often fatal infectious disease caused by Yersinia pestis (Y. pestis). Humoral immune responses provide critical protective immunity against plague. Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge. In the current study, we further evaluated whether the use of a DNA priming immunization is able to enhance the immunogenicity of a recombinant LcrV protein vaccine, and in particular, the development of LcrV-specific B cells. Our data indicate that DNA immunization was able to elicit high-level LcrV antibody responses when used alone or as part of a prime-boost immunization approach. Most significantly, DNA immunization was also able to increase the levels of LcrV-specific B cell development. The finding that DNA immunization can enhance antigen-specific B cell responses is highly significant and will help guide similar studies in other model antigen systems. Full article

Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, CA, USA), VAX004 (Vaxgen, Inc.), HIV-1 Vaccine Trials Network (HVTN) 502 (Step), HVTN 503 (Phambili), RV144 (sponsored by the U.S. Military HIV Research Program, MHRP) and HVTN 505). Cellular, humoral, host genetic and virus sieve analyses of these human clinical trials each can provide information that may point to potentially protective mechanisms for vaccine-induced immunity. Critical to staying on the path toward development of an efficacious vaccine is utilizing information from previous human and non-human primate studies in concert with new discoveries of basic HIV-1 host-virus interactions. One way that past discoveries from correlate analyses can lead to novel inventions or new pathways toward vaccine efficacy is to examine the intersections where different components of the correlate analyses overlap (e.g., virus sieve analysis combined with humoral correlates) that can point to mechanistic hypotheses. Additionally, differences in durability among vaccine-induced T- and B-cell responses indicate that time post-vaccination is an important variable. Thus, understanding the nature of protective responses, the degree to which such responses have, or have not, as yet, been induced by previous vaccine trials and the design of strategies to induce durable T- and B-cell responses are critical to the development of a protective HIV-1 vaccine. Full article

In this brief review, we discuss immune tolerance as a factor that determines the magnitude and quality of serum antibody responses to HIV-1 infection and vaccination in the context of recent work. We propose that many conserved, neutralizing epitopes of HIV-1 are weakly immunogenic because they mimic host antigens. In consequence, B cells that strongly bind these determinants are removed by the physiological process of immune tolerance. This structural mimicry may represent a significant impediment to designing protective HIV-1 vaccines, but we note that several vaccine strategies may be able to mitigate this evolutionary adaptation of HIV and other microbial pathogens. Full article