Superiority in rhesus macaques of targeting HIV-1 Env gp140 to CD40 versus LOX-1 in combination with replication-competent NYVAC-KC for induction of Env-specific antibody and T cell responses

Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D. Tomaras, David C. Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E. Foulds, Shing Fen Kao, Xuesong Yu, Alicia Sato, Nicole L. Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres SalazarSteve Self, William Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly-ICLC adjuvant either alone or coadministered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly-ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to a P value of 0.01) than in a group without poly-ICLC. The responses were robust and cross-reactive and contained antibodies specific to multiple epitopes within gp140, including the C1, C2, V1, V2, and V3, C4, C5, and gp41 immunodominant regions. The DC-targeting vaccines also elicited modest serum Env-specific IgA responses. All groups gave serum neutralization activity limited to tier 1 viruses and antibodydependent cytotoxicity responses (ADCC) after DC-targeting boosts. Furthermore, CD4+ and CD8+ T cell responses specific to multiple Env epitopes were strongly boosted by the DC-targeting vaccines plus poly-ICLC. Together, these results indicate that prime-boost immunization via NYVAC-KC and either anti-CD40.Env gp140/poly- ICLC or anti-LOX-1.Env gp140/poly-ICLC induced balanced antibody and T cell responses against HIV-1 Env. Coadministration of NYVAC-KC with the DC-targeting vaccines increased T cell responses but had minimal effects on antibody responses except for suppressing serum IgA responses. Overall, targeting Env to CD40 gave more robust T cell and serum antibody responses with broader epitope representation and greater durability than with LOX-1.

Original languageEnglish (US)
Article numbere01596-16
JournalJournal of virology
Volume91
Issue number9
DOIs
StatePublished - May 1 2017

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Keywords

  • Dendritic cells
  • HIV-1
  • Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Zurawski, G., Shen, X., Zurawski, S., Tomaras, G. D., Montefiori, D. C., Roederer, M., Ferrari, G., Lacabaratz, C., Klucar, P., Wang, Z., Foulds, K. E., Kao, S. F., Yu, X., Sato, A., Yates, N. L., LaBranche, C., Stanfield-Oakley, S., Kibler, K., Jacobs, B., ... Levy, Y. (2017). Superiority in rhesus macaques of targeting HIV-1 Env gp140 to CD40 versus LOX-1 in combination with replication-competent NYVAC-KC for induction of Env-specific antibody and T cell responses. Journal of virology, 91(9), [e01596-16]. https://doi.org/10.1128/JVI.01596-16