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 Salazar & 8 others Steve Self, William Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

Fingerprint

dendritic cells
Human immunodeficiency virus 1
Macaca mulatta
Dendritic Cells
T-lymphocytes
T-Lymphocytes
antibodies
Antibodies
vaccines
Vaccines
epitopes
Epitopes
Serum
Immunoglobulin A
Antibody Formation
HIV-1
Poxviridae
recombinant antibodies
Antibodies, Monoclonal, Humanized
Immunodominant Epitopes

Keywords

  • Dendritic cells
  • HIV-1
  • Vaccines

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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

In: Journal of Virology, Vol. 91, No. 9, e01596-16, 01.05.2017.

Research output: Contribution to journalArticle

Zurawski, G, Shen, X, Zurawski, S, Tomaras, GD, Montefiori, DC, Roederer, M, Ferrari, G, Lacabaratz, C, Klucar, P, Wang, Z, Foulds, KE, Kao, SF, Yu, X, Sato, A, Yates, NL, LaBranche, C, Stanfield-Oakley, S, Kibler, K, Jacobs, B, Salazar, A, Self, S, Fulp, W, Gottardo, R, Galmin, L, Weiss, D, Cristillo, A, Pantaleo, G & 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, vol. 91, no. 9, e01596-16. https://doi.org/10.1128/JVI.01596-16
Zurawski, Gerard ; Shen, Xiaoying ; Zurawski, Sandra ; Tomaras, Georgia D. ; Montefiori, David C. ; Roederer, Mario ; Ferrari, Guido ; Lacabaratz, Christine ; Klucar, Peter ; Wang, Zhiqing ; Foulds, Kathryn E. ; Kao, Shing Fen ; Yu, Xuesong ; Sato, Alicia ; Yates, Nicole L. ; LaBranche, Celia ; Stanfield-Oakley, Sherry ; Kibler, Karen ; Jacobs, Bertram ; Salazar, Andres ; Self, Steve ; Fulp, William ; Gottardo, Raphael ; Galmin, Lindsey ; Weiss, Deborah ; Cristillo, Anthony ; Pantaleo, Giuseppe ; Levy, Yves. / 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. In: Journal of Virology. 2017 ; Vol. 91, No. 9.
@article{b5a9131cc8b647e881ace93d3bc2523f,
title = "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",
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.",
keywords = "Dendritic cells, HIV-1, Vaccines",
author = "Gerard Zurawski and Xiaoying Shen and Sandra Zurawski and Tomaras, {Georgia D.} and Montefiori, {David C.} and Mario Roederer and Guido Ferrari and Christine Lacabaratz and Peter Klucar and Zhiqing Wang and Foulds, {Kathryn E.} and Kao, {Shing Fen} and Xuesong Yu and Alicia Sato and Yates, {Nicole L.} and Celia LaBranche and Sherry Stanfield-Oakley and Karen Kibler and Bertram Jacobs and Andres Salazar and Steve Self and William Fulp and Raphael Gottardo and Lindsey Galmin and Deborah Weiss and Anthony Cristillo and Giuseppe Pantaleo and Yves Levy",
year = "2017",
month = "5",
day = "1",
doi = "10.1128/JVI.01596-16",
language = "English (US)",
volume = "91",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=85017548168&partnerID=8YFLogxK

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

VL - 91

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 9

M1 - e01596-16

ER -