A major hurdle in the development of a global HIV-1 vaccine is viral diversity. For close to three decades, HIV vaccine development has focused on either the induction of T cell immune responses or antibody responses, and only rarely on both components. After the failure of the STEP trial, the scientific community concluded that a T cell-based vaccine would likely not be protective if the T cell immune responses were elicited against only a few dominant epitopes. Similarly, for vaccines focusing on antibody responses, one of the main criticisms after VaxGens failed Phase III trials was on the limited antigen breadth included in the two formulations used. The successes of polyvalent vaccine approaches against other antigenically variable pathogens encourage implementation of the same approach for the design of HIV-1 vaccines. A review of the existing HIV-1 vaccination approaches based on the polyvalent principle is included here to provide a historical perspective for the current effort of developing a polyvalent HIV-1 vaccine. Results summarized in this review provide a clear indication that the polyvalent approach is a viable one for the future development of an effective HIV vaccine.
Keywords: HIV-1, vaccine, subtypes, neutralizing antibodies, cytotoxic T lymphocytes, polyvalent vaccine, T cell immune responses, Global AIDS Epidemic, viral diversity, gorilla simian immunodeficiency virus (SIVgor), circulating recombinant forms (CRFs), VaxGen's failed Phase III trials, monoclonal antibodies (mAbs), antigenicity, immunogenicity, immunization, placebo, poliomyelitis, epidemic human diseases, flu pandemics, pneumococcus, immunocompromised individuals, human papillomavirus (HPV), vaccination technology, cell-mediated immunity, virus-specific T helper cells, superinfection, heterologous viruses, antibodyantigen interaction, ENV VACCINE, DNA-based vaccination, PhenoSense assay, pseudoviruses, monovalent antigens, Gag-specific cell-mediated immune responses, CD4 T-helper cells, mosaic vaccines, computational optimization method, synergistic effect
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