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 Article
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.
Full Text
Duke Authors
Cited Authors
- Hulot, SL; Korber, B; Giorgi, EE; Vandergrift, N; Saunders, KO; Balachandran, H; Mach, LV; Lifton, MA; Pantaleo, G; Tartaglia, J; Phogat, S; Jacobs, B; Kibler, K; Perdiguero, B; Gomez, CE; Esteban, M; Rosati, M; Felber, BK; Pavlakis, GN; Parks, R; Lloyd, K; Sutherland, L; Scearce, R; Letvin, NL; Seaman, MS; Alam, SM; Montefiori, D; Liao, H-X; Haynes, BF; Santra, S
Published Date
- June 2015
Published In
Volume / Issue
- 89 / 12
Start / End Page
- 6462 - 6480
PubMed ID
- 25855741
Pubmed Central ID
- 25855741
Electronic International Standard Serial Number (EISSN)
- 1098-5514
Digital Object Identifier (DOI)
- 10.1128/JVI.00383-15
Language
- eng
Conference Location
- United States