Combination adenovirus and protein vaccines prevent infection or reduce viral burden after heterologous clade C simian-human immunodeficiency virus mucosal challenge

Delphine Malherbe, Jason Mendy, Lo Vang, Philip T. Barnette, Jason Reed, Samir K. Lakhashe, Joshua Owuor, Johannes S. Gach, Alfred W. Legasse, Michael Axthelm, Celia C. LaBranche, David Montefiori, Donald N. Forthal, Byung Park, James M. Wilson, James H. McLinden, Jinhua Xiang, Jack T. Stapleton, Jonah Sacha, Barton F. Haynes & 6 others Hua Xin Liao, Ruth M. Ruprecht, Jonathan Smith, Marc Gurwith, Nancy Haigwood, Jeff Alexander

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with nonreplicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge. In both vaccine groups, plasma and buccal Env-specific IgG, tier 1 heterologous neutralizing antibodies, and antibody-dependent cell-mediated viral inhibition were readily generated. High Env-specific T cell responses elicited in all vaccinees were significantly greater than responses targeting Gag. After three intrarectal exposures to heterologous tier 1 clade C SHIV, all 10 sham-vaccinated controls were infected, whereas 4/10 SAd7- and 3/10 Ad4-vaccinated macaques remained uninfected or maintained tightly controlled plasma viremia. Time to infection was significantly delayed in SAd7- vaccinated macaques compared to the controls. Cell-associated and plasma virus levels were significantly lower in each group of vaccinated macaques compared to controls; the lowest plasma viral burden was found in animals vaccinated with the SAd7 vectors, suggesting superior immunity conferred by the replicating simian vectors. Furthermore, higher V1V2-specific binding antibody titers correlated with viral control in the SAd7 vaccine group. Thus, recombinant Ad plus protein vaccines generated humoral and cellular immunity that was effective in either protecting from SHIV acquisition or significantly reducing viremia in animals that became infected, consequently supporting additional development of replicating Ad vectors as HIV vaccines.

Original languageEnglish (US)
Article numbere01092-17
JournalJournal of Virology
Volume92
Issue number2
DOIs
StatePublished - Jan 1 2018

Fingerprint

Adenovirus Vaccines
Combined Vaccines
Simian Immunodeficiency Virus
Human immunodeficiency virus
Macaca
Adenoviridae
viral load
Viral Load
Immunity
AIDS Vaccines
Vaccines
Viremia
HIV
vaccines
Infection
infection
GB virus C
env Gene Products
immunity
Heterophile Antibodies

Keywords

  • Adenovirus
  • Adenovirus vector
  • Correlate of protection
  • HIV vaccine
  • Neutralizing antibody
  • Rhesus macaque
  • SHIV challenge
  • Simian human immunodeficiency virus
  • V1V2-specific antibody
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Combination adenovirus and protein vaccines prevent infection or reduce viral burden after heterologous clade C simian-human immunodeficiency virus mucosal challenge. / Malherbe, Delphine; Mendy, Jason; Vang, Lo; Barnette, Philip T.; Reed, Jason; Lakhashe, Samir K.; Owuor, Joshua; Gach, Johannes S.; Legasse, Alfred W.; Axthelm, Michael; LaBranche, Celia C.; Montefiori, David; Forthal, Donald N.; Park, Byung; Wilson, James M.; McLinden, James H.; Xiang, Jinhua; Stapleton, Jack T.; Sacha, Jonah; Haynes, Barton F.; Liao, Hua Xin; Ruprecht, Ruth M.; Smith, Jonathan; Gurwith, Marc; Haigwood, Nancy; Alexander, Jeff.

In: Journal of Virology, Vol. 92, No. 2, e01092-17, 01.01.2018.

Research output: Contribution to journalArticle

Malherbe, D, Mendy, J, Vang, L, Barnette, PT, Reed, J, Lakhashe, SK, Owuor, J, Gach, JS, Legasse, AW, Axthelm, M, LaBranche, CC, Montefiori, D, Forthal, DN, Park, B, Wilson, JM, McLinden, JH, Xiang, J, Stapleton, JT, Sacha, J, Haynes, BF, Liao, HX, Ruprecht, RM, Smith, J, Gurwith, M, Haigwood, N & Alexander, J 2018, 'Combination adenovirus and protein vaccines prevent infection or reduce viral burden after heterologous clade C simian-human immunodeficiency virus mucosal challenge', Journal of Virology, vol. 92, no. 2, e01092-17. https://doi.org/10.1128/JVI.01092-17
Malherbe, Delphine ; Mendy, Jason ; Vang, Lo ; Barnette, Philip T. ; Reed, Jason ; Lakhashe, Samir K. ; Owuor, Joshua ; Gach, Johannes S. ; Legasse, Alfred W. ; Axthelm, Michael ; LaBranche, Celia C. ; Montefiori, David ; Forthal, Donald N. ; Park, Byung ; Wilson, James M. ; McLinden, James H. ; Xiang, Jinhua ; Stapleton, Jack T. ; Sacha, Jonah ; Haynes, Barton F. ; Liao, Hua Xin ; Ruprecht, Ruth M. ; Smith, Jonathan ; Gurwith, Marc ; Haigwood, Nancy ; Alexander, Jeff. / Combination adenovirus and protein vaccines prevent infection or reduce viral burden after heterologous clade C simian-human immunodeficiency virus mucosal challenge. In: Journal of Virology. 2018 ; Vol. 92, No. 2.
@article{8c63eaf4af7f4e61b19c6236b56c68fd,
title = "Combination adenovirus and protein vaccines prevent infection or reduce viral burden after heterologous clade C simian-human immunodeficiency virus mucosal challenge",
abstract = "HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with nonreplicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge. In both vaccine groups, plasma and buccal Env-specific IgG, tier 1 heterologous neutralizing antibodies, and antibody-dependent cell-mediated viral inhibition were readily generated. High Env-specific T cell responses elicited in all vaccinees were significantly greater than responses targeting Gag. After three intrarectal exposures to heterologous tier 1 clade C SHIV, all 10 sham-vaccinated controls were infected, whereas 4/10 SAd7- and 3/10 Ad4-vaccinated macaques remained uninfected or maintained tightly controlled plasma viremia. Time to infection was significantly delayed in SAd7- vaccinated macaques compared to the controls. Cell-associated and plasma virus levels were significantly lower in each group of vaccinated macaques compared to controls; the lowest plasma viral burden was found in animals vaccinated with the SAd7 vectors, suggesting superior immunity conferred by the replicating simian vectors. Furthermore, higher V1V2-specific binding antibody titers correlated with viral control in the SAd7 vaccine group. Thus, recombinant Ad plus protein vaccines generated humoral and cellular immunity that was effective in either protecting from SHIV acquisition or significantly reducing viremia in animals that became infected, consequently supporting additional development of replicating Ad vectors as HIV vaccines.",
keywords = "Adenovirus, Adenovirus vector, Correlate of protection, HIV vaccine, Neutralizing antibody, Rhesus macaque, SHIV challenge, Simian human immunodeficiency virus, V1V2-specific antibody, Vaccine",
author = "Delphine Malherbe and Jason Mendy and Lo Vang and Barnette, {Philip T.} and Jason Reed and Lakhashe, {Samir K.} and Joshua Owuor and Gach, {Johannes S.} and Legasse, {Alfred W.} and Michael Axthelm and LaBranche, {Celia C.} and David Montefiori and Forthal, {Donald N.} and Byung Park and Wilson, {James M.} and McLinden, {James H.} and Jinhua Xiang and Stapleton, {Jack T.} and Jonah Sacha and Haynes, {Barton F.} and Liao, {Hua Xin} and Ruprecht, {Ruth M.} and Jonathan Smith and Marc Gurwith and Nancy Haigwood and Jeff Alexander",
year = "2018",
month = "1",
day = "1",
doi = "10.1128/JVI.01092-17",
language = "English (US)",
volume = "92",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Combination adenovirus and protein vaccines prevent infection or reduce viral burden after heterologous clade C simian-human immunodeficiency virus mucosal challenge

AU - Malherbe, Delphine

AU - Mendy, Jason

AU - Vang, Lo

AU - Barnette, Philip T.

AU - Reed, Jason

AU - Lakhashe, Samir K.

AU - Owuor, Joshua

AU - Gach, Johannes S.

AU - Legasse, Alfred W.

AU - Axthelm, Michael

AU - LaBranche, Celia C.

AU - Montefiori, David

AU - Forthal, Donald N.

AU - Park, Byung

AU - Wilson, James M.

AU - McLinden, James H.

AU - Xiang, Jinhua

AU - Stapleton, Jack T.

AU - Sacha, Jonah

AU - Haynes, Barton F.

AU - Liao, Hua Xin

AU - Ruprecht, Ruth M.

AU - Smith, Jonathan

AU - Gurwith, Marc

AU - Haigwood, Nancy

AU - Alexander, Jeff

PY - 2018/1/1

Y1 - 2018/1/1

N2 - HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with nonreplicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge. In both vaccine groups, plasma and buccal Env-specific IgG, tier 1 heterologous neutralizing antibodies, and antibody-dependent cell-mediated viral inhibition were readily generated. High Env-specific T cell responses elicited in all vaccinees were significantly greater than responses targeting Gag. After three intrarectal exposures to heterologous tier 1 clade C SHIV, all 10 sham-vaccinated controls were infected, whereas 4/10 SAd7- and 3/10 Ad4-vaccinated macaques remained uninfected or maintained tightly controlled plasma viremia. Time to infection was significantly delayed in SAd7- vaccinated macaques compared to the controls. Cell-associated and plasma virus levels were significantly lower in each group of vaccinated macaques compared to controls; the lowest plasma viral burden was found in animals vaccinated with the SAd7 vectors, suggesting superior immunity conferred by the replicating simian vectors. Furthermore, higher V1V2-specific binding antibody titers correlated with viral control in the SAd7 vaccine group. Thus, recombinant Ad plus protein vaccines generated humoral and cellular immunity that was effective in either protecting from SHIV acquisition or significantly reducing viremia in animals that became infected, consequently supporting additional development of replicating Ad vectors as HIV vaccines.

AB - HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with nonreplicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge. In both vaccine groups, plasma and buccal Env-specific IgG, tier 1 heterologous neutralizing antibodies, and antibody-dependent cell-mediated viral inhibition were readily generated. High Env-specific T cell responses elicited in all vaccinees were significantly greater than responses targeting Gag. After three intrarectal exposures to heterologous tier 1 clade C SHIV, all 10 sham-vaccinated controls were infected, whereas 4/10 SAd7- and 3/10 Ad4-vaccinated macaques remained uninfected or maintained tightly controlled plasma viremia. Time to infection was significantly delayed in SAd7- vaccinated macaques compared to the controls. Cell-associated and plasma virus levels were significantly lower in each group of vaccinated macaques compared to controls; the lowest plasma viral burden was found in animals vaccinated with the SAd7 vectors, suggesting superior immunity conferred by the replicating simian vectors. Furthermore, higher V1V2-specific binding antibody titers correlated with viral control in the SAd7 vaccine group. Thus, recombinant Ad plus protein vaccines generated humoral and cellular immunity that was effective in either protecting from SHIV acquisition or significantly reducing viremia in animals that became infected, consequently supporting additional development of replicating Ad vectors as HIV vaccines.

KW - Adenovirus

KW - Adenovirus vector

KW - Correlate of protection

KW - HIV vaccine

KW - Neutralizing antibody

KW - Rhesus macaque

KW - SHIV challenge

KW - Simian human immunodeficiency virus

KW - V1V2-specific antibody

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=85039901121&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039901121&partnerID=8YFLogxK

U2 - 10.1128/JVI.01092-17

DO - 10.1128/JVI.01092-17

M3 - Article

VL - 92

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

M1 - e01092-17

ER -