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Comparison of immunogenicity in rhesus macaques of transmitted-founder, HIV-1 group M consensus, and trivalent mosaic envelope vaccines formulated as a DNA prime, NYVAC, and envelope protein boost
Hulot, S. L., Korber, B., Giorgi, E. E., Vandergrift, N., Saunders, K. O., Balachandran, H., Mach, L. V., Lifton, M. A., Pantaleo, G., Tartaglia, J., Phogat, S., Jacobs, B., Kibler, K., Perdiguero, B., Gomez, C. E., Esteban, M., Rosati, M., Felber, B. K., Pavlakis, G. N., ... Santra, S. (2015). Comparison of immunogenicity in rhesus macaques of transmitted-founder, HIV-1 group M consensus, and trivalent mosaic envelope vaccines formulated as a DNA prime, NYVAC, and envelope protein boost. Journal of Virology, 89(12), 6462-6480. https://doi.org/10.1128/JVI.00383-15
UNLABELLED: An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4(+) and CD8(+) T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using in silico-designed centralized immunogens for global HIV-1 vaccine development strategies.
IMPORTANCE: There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1 acquisition. This nonhuman primate study demonstrates that in silico-designed global HIV-1 immunogens, designed for a human clinical trial, are capable of eliciting not only T lymphocyte responses but also potent anti-Env antibody responses.
