Girard MP, Osmanov SK, Kieny MP. A review of vaccine research and development: the human immunodeficiency virus (HIV)

University Paris 7, 39 rue Seignemartin, FR 69008 Lyon, France.
Vaccine (Impact Factor: 3.62). 06/2006; 24(19):4062-81. DOI: 10.1016/j.vaccine.2006.02.031
Source: PubMed


Since the discovery of AIDS in 1981, the global spread of HIV has reached pandemic proportions, representing a global developmental and public health threat. The development of a safe, globally effective and affordable HIV vaccine offers the best hope for the future control of the pandemic. Significant progress has been made over the past years in the areas of basic virology, immunology, pathogenesis of HIV/AIDS and the development of antiretroviral drugs. However, the development of an HIV vaccine faces formidable scientific challenges related to the high genetic variability of the virus, the lack of immune correlates of protection, limitations with the existing animal models and logistical problems associated with the conduct of multiple clinical trials. More than 35 vaccine candidates have been tested in Phase I/II clinical trials, involving more than 10,000 volunteers, and two Phase III trials have been completed, themselves involving more than 7500 volunteers. Multiple vaccine concepts and vaccination strategies have been tested, including DNA vaccines, subunit vaccines, live vectored recombinant vaccines and various prime-boost vaccine combinations. This article reviews the state of the art in HIV vaccine development, summarizes the results obtained so far and discusses the challenges to be met in the development of the various vaccine candidates.

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    • "However, one of the main challenges in the design of an effective vaccine for HIV consists of eliciting potent, broad and long-lasting cellular (CTLs) and humoral immune responses (Excler et al. 2014). A widely used approach for developing HIV vaccine candidates employs recombinant DNA technology (Dong et al. 2005; Girard et al. 2006; Graham et al. 2010; Haynes et al. 2006; White and Meng 2012; Zolla-Pazner et al. 2008). Potential HIV vaccines are multi-epitope chimeric proteins that contain selected protective epitopes in a single antigen, while excluding the non-protective epitopes. "
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    ABSTRACT: Key message The first report on the recombinant production of a candidate vaccine in the moss system. Abstract The need for economical and efficient platforms for vaccine production demands the exploration of emerging host organisms. In this study, the production of an antigenic protein is reported employing the moss Physcomitrella patens as an expression host. A multi-epitope protein from the Human Immunodeficiency Virus (HIV) based on epitopes from gp120 and gp41 was designed as a candidate subunit vaccine and named poly-HIV. Transgenic moss plants were generated carrying the corresponding poly-HIV transgene under a novel moss promoter and subsequently seven positive lines were confirmed by PCR. The poly-HIV protein accumulated up to 3.7 µg g−1 fresh weight in protonema cultures. Antigenic and immunogenic properties of the moss-produced recombinant poly-HIV are evidenced by Western blots and by mice immunization assays. The elicitation of specific antibodies in mice was observed, reflecting the immunogenic potential of this moss-derived HIV antigen. This is the first report on the production of a potential vaccine in the moss system and opens the avenue for glycoengineering approaches for the production of HIV human-like glycosylated antigens as well as other vaccine prototypes under GMP conditions in moss bioreactors.
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    • "These include the polysaccharide or protein subunit vaccines. Finally, one of the newest concepts in vaccine technology pertains to DNA plasmids that, upon in vivo administration, successfully express proteins that induce an immune response [2]. The spectrum of existing vaccine formulations is constantly expanding, as an ever growing number of studies are underway globally to figure out the optimal conditions for vaccine administration. "
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    ABSTRACT: In today's medical industry, the range of vaccines that exist for administration in humans represents an eclectic variety of forms and immunologic mechanisms. Namely, these are the live attenuated viruses, inactivated viruses, subunit proteins, and virus-like particles for treating virus-caused diseases, as well as the bacterial-based polysaccharide, protein, and conjugated vaccines. Currently, a new approach to vaccination is being investigated with the concept of DNA vaccines. As an alternative delivery route to enhance the vaccination efficacy, microneedles have been devised to target the rich network of immunologic antigen-presenting cells in the dermis and epidermis layers under the skin. Numerous studies have outlined the parameters of microneedle delivery of a wide range of vaccines, revealing comparable or higher immunogenicity to conventional intramuscular routes, overall level of stability, and dose-sparing advantages. Furthermore, recent mechanism studies have begun to successfully elucidate the biological mechanisms behind microneedle vaccination. This paper describes the current status of microneedle vaccine research.
    Full-text · Article · Jan 2014
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    • "Protein subunit vaccines are usually not very efficient in inducing T cell responses so it remains to be established in what formulation the immunogen should be delivered. Many possibilities are being developed, from soluble proteins to DNA plasmids and viral vectors, which can all be used in multiple prime-boost combinations (Girard et al., 2006; McElrath and Haynes, 2010). Fusing Env immunogens to costimulatory molecules may be an alternative approach for aiding B cell targeting and activation (Melchers et al., 2011, 2012). "
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    ABSTRACT: The need for an effective vaccine to prevent the global spread of human immunodeficiency virus type 1 (HIV-1) is well recognized. Passive immunization and challenge studies in non-human primates testify that broadly neutralizing antibodies (BrNAbs) can accomplish protection against infection. In recent years, the introduction of new techniques has facilitated the discovery of an unprecedented number of new human BrNAbs that target and delineate diverse conserved epitopes on the envelope glycoprotein spike (Env). The epitopes of these BrNAbs can serve as templates for immunogen design aimed to induce similar antibodies. Here we will review the characteristics of the different classes of BrNAbs and their target epitopes, as well as factors associated with their development and implications for vaccine design.
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