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

Sandrine L. Hulot, Bette Korber, Elena E. Giorgi, Nathan Vandergrift, Kevin O. Saunders, Harikrishnan Balachandran, Linh V. Mach, Michelle A. Lifton, Giuseppe Pantaleo, Jim Tartaglia, Sanjay Phogat, Bertram Jacobs, Karen Kibler, Beatriz Perdiguero, Carmen E. Gomez, Mariano Esteban, Margherita Rosati, Barbara K. Felber, George N. Pavlakis, Robert Parks & 10 others Krissey Lloyd, Laura Sutherland, Richard Scearce, Norman L. Letvin, Michael S. Seaman, S. Munir Alam, David Montefiori, Hua Xin Liao, Barton F. Haynes, Sampa Santra

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4<sup>+</sup> and CD8<sup>+</sup> 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 groupMconsensus 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.

Original languageEnglish (US)
Pages (from-to)6462-6480
Number of pages19
JournalJournal of Virology
Volume89
Issue number12
DOIs
StatePublished - 2015

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Human immunodeficiency virus 1
Macaca mulatta
env Gene Products
HIV-1
T-Lymphocyte Epitopes
Vaccines
immune response
vaccines
antigens
Neutralizing Antibodies
DNA
T-lymphocytes
epitopes
Viruses
T-Lymphocytes
Proteins
Recombinant DNA
proteins
Antibodies
neutralizing antibodies

ASJC Scopus subject areas

  • Immunology
  • Virology

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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, Sandrine L.; Korber, Bette; Giorgi, Elena E.; Vandergrift, Nathan; Saunders, Kevin O.; Balachandran, Harikrishnan; Mach, Linh V.; Lifton, Michelle A.; Pantaleo, Giuseppe; Tartaglia, Jim; Phogat, Sanjay; Jacobs, Bertram; Kibler, Karen; Perdiguero, Beatriz; Gomez, Carmen E.; Esteban, Mariano; Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.; Parks, Robert; Lloyd, Krissey; Sutherland, Laura; Scearce, Richard; Letvin, Norman L.; Seaman, Michael S.; Alam, S. Munir; Montefiori, David; Liao, Hua Xin; Haynes, Barton F.; Santra, Sampa.

In: Journal of Virology, Vol. 89, No. 12, 2015, p. 6462-6480.

Research output: Contribution to journalArticle

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, HX, Haynes, BF & 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, vol. 89, no. 12, pp. 6462-6480. https://doi.org/10.1128/JVI.00383-15
Hulot, Sandrine L. ; Korber, Bette ; Giorgi, Elena E. ; Vandergrift, Nathan ; Saunders, Kevin O. ; Balachandran, Harikrishnan ; Mach, Linh V. ; Lifton, Michelle A. ; Pantaleo, Giuseppe ; Tartaglia, Jim ; Phogat, Sanjay ; Jacobs, Bertram ; Kibler, Karen ; Perdiguero, Beatriz ; Gomez, Carmen E. ; Esteban, Mariano ; Rosati, Margherita ; Felber, Barbara K. ; Pavlakis, George N. ; Parks, Robert ; Lloyd, Krissey ; Sutherland, Laura ; Scearce, Richard ; Letvin, Norman L. ; Seaman, Michael S. ; Alam, S. Munir ; Montefiori, David ; Liao, Hua Xin ; Haynes, Barton F. ; Santra, Sampa. / 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. In: Journal of Virology. 2015 ; Vol. 89, No. 12. pp. 6462-6480.
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