HIV DNA-adenovirus multiclade envelope vaccine induces gp41 antibody immunodominance in rhesus macaques

Qifeng Han, Wilton B. Williams, Kevin O. Saunders, Kelly E. Seaton, Kevin J. Wiehe, Nathan Vandergrift, Tarra A. Von Holle, Ashley M. Trama, Robert J. Parks, Kan Luo, Thaddeus C. Gurley, Thomas B. Kepler, Dawn J. Marshall, David C. Montefiori, Laura L. Sutherland, Munir S. Alam, John F. Whitesides, Cindy M. Bowman, Sallie R. Permar, Barney S. GrahamJohn R. Mascola, Patrick C. Seed, Koen K.A. Van Rompay, Georgia D. Tomaras, M. Anthony Moody, Barton F. Haynes*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41- reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.

Original languageEnglish (US)
Article numbere00923-17
JournalJournal of virology
Volume91
Issue number21
DOIs
StatePublished - Nov 1 2017

Keywords

  • Gp41
  • HIV-1 envelope
  • HIV-1 vaccine
  • Microbiome
  • Rhesus macaques

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Han, Q., Williams, W. B., Saunders, K. O., Seaton, K. E., Wiehe, K. J., Vandergrift, N., Von Holle, T. A., Trama, A. M., Parks, R. J., Luo, K., Gurley, T. C., Kepler, T. B., Marshall, D. J., Montefiori, D. C., Sutherland, L. L., Alam, M. S., Whitesides, J. F., Bowman, C. M., Permar, S. R., ... Haynes, B. F. (2017). HIV DNA-adenovirus multiclade envelope vaccine induces gp41 antibody immunodominance in rhesus macaques. Journal of virology, 91(21), [e00923-17]. https://doi.org/10.1128/JVI.00923-17