TY - JOUR
T1 - 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
AU - Zurawski, Gerard
AU - Shen, Xiaoying
AU - Zurawski, Sandra
AU - Tomaras, Georgia D.
AU - Montefiori, David C.
AU - Roederer, Mario
AU - Ferrari, Guido
AU - Lacabaratz, Christine
AU - Klucar, Peter
AU - Wang, Zhiqing
AU - Foulds, Kathryn E.
AU - Kao, Shing Fen
AU - Yu, Xuesong
AU - Sato, Alicia
AU - Yates, Nicole L.
AU - LaBranche, Celia
AU - Stanfield-Oakley, Sherry
AU - Kibler, Karen
AU - Jacobs, Bertram
AU - Salazar, Andres
AU - Self, Steve
AU - Fulp, William
AU - Gottardo, Raphael
AU - Galmin, Lindsey
AU - Weiss, Deborah
AU - Cristillo, Anthony
AU - Pantaleo, Giuseppe
AU - Levy, Yves
N1 - Publisher Copyright:
© 2017 American Society for Microbiology.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
KW - Dendritic cells
KW - HIV-1
KW - Vaccines
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UR - http://www.scopus.com/inward/citedby.url?scp=85017548168&partnerID=8YFLogxK
U2 - 10.1128/JVI.01596-16
DO - 10.1128/JVI.01596-16
M3 - Article
C2 - 28202751
AN - SCOPUS:85017548168
SN - 0022-538X
VL - 91
JO - Journal of virology
JF - Journal of virology
IS - 9
M1 - e01596-16
ER -