Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

Benedikt Asbach, Karen Kibler, Josef Köstler, Beatriz Perdiguero, Nicole L. Yates, Sherry Stanfield-Oakley, Georgia D. Tomaras, Shing Fen Kao, Kathryn E. Foulds, Mario Roederer, Michael S. Seaman, David C. Montefiori, Robert Parks, Guido Ferrari, Donald N. Forthal, Sanjay Phogat, James Tartaglia, Susan W. Barnett, Steven G. Self, Raphael Gottardo & 9 others Anthony D. Cristillo, Deborah E. Weiss, Lindsey Galmin, Song Ding, Jonathan L. Heeney, Mariano Esteban, Bertram Jacobs, Giuseppe Pantaleo, Ralf Wagner

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens.IMPORTANCE The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities-conventional intramuscular delivery and percutaneous delivery by scarification-impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.

Original languageEnglish (US)
JournalJournal of virology
Volume93
Issue number3
DOIs
StatePublished - Feb 1 2019

Fingerprint

Poxviridae
DNA Vaccines
recombinant vaccines
Human immunodeficiency virus 1
HIV-1
immune response
AIDS Vaccines
Proteins
antibodies
T-Lymphocytes
proteins
T-lymphocytes
Primates
Vaccination
humoral immunity
env Gene Products
Antibody-Dependent Cell Cytotoxicity
vaccination
Antibodies
Vaccinia virus

Keywords

  • antibody responses
  • DNA vaccine
  • Gag-Pol-Nef
  • gp140
  • human immunodeficiency virus
  • nonhuman primates
  • NYVAC
  • NYVAC-KC
  • T cell responses
  • vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost. / Asbach, Benedikt; Kibler, Karen; Köstler, Josef; Perdiguero, Beatriz; Yates, Nicole L.; Stanfield-Oakley, Sherry; Tomaras, Georgia D.; Kao, Shing Fen; Foulds, Kathryn E.; Roederer, Mario; Seaman, Michael S.; Montefiori, David C.; Parks, Robert; Ferrari, Guido; Forthal, Donald N.; Phogat, Sanjay; Tartaglia, James; Barnett, Susan W.; Self, Steven G.; Gottardo, Raphael; Cristillo, Anthony D.; Weiss, Deborah E.; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L.; Esteban, Mariano; Jacobs, Bertram; Pantaleo, Giuseppe; Wagner, Ralf.

In: Journal of virology, Vol. 93, No. 3, 01.02.2019.

Research output: Contribution to journalArticle

Asbach, B, Kibler, K, Köstler, J, Perdiguero, B, Yates, NL, Stanfield-Oakley, S, Tomaras, GD, Kao, SF, Foulds, KE, Roederer, M, Seaman, MS, Montefiori, DC, Parks, R, Ferrari, G, Forthal, DN, Phogat, S, Tartaglia, J, Barnett, SW, Self, SG, Gottardo, R, Cristillo, AD, Weiss, DE, Galmin, L, Ding, S, Heeney, JL, Esteban, M, Jacobs, B, Pantaleo, G & Wagner, R 2019, 'Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost', Journal of virology, vol. 93, no. 3. https://doi.org/10.1128/JVI.01529-18
Asbach, Benedikt ; Kibler, Karen ; Köstler, Josef ; Perdiguero, Beatriz ; Yates, Nicole L. ; Stanfield-Oakley, Sherry ; Tomaras, Georgia D. ; Kao, Shing Fen ; Foulds, Kathryn E. ; Roederer, Mario ; Seaman, Michael S. ; Montefiori, David C. ; Parks, Robert ; Ferrari, Guido ; Forthal, Donald N. ; Phogat, Sanjay ; Tartaglia, James ; Barnett, Susan W. ; Self, Steven G. ; Gottardo, Raphael ; Cristillo, Anthony D. ; Weiss, Deborah E. ; Galmin, Lindsey ; Ding, Song ; Heeney, Jonathan L. ; Esteban, Mariano ; Jacobs, Bertram ; Pantaleo, Giuseppe ; Wagner, Ralf. / Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost. In: Journal of virology. 2019 ; Vol. 93, No. 3.
@article{dcb294c8799842269d3aefc33cf159bb,
title = "Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost",
abstract = "The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens.IMPORTANCE The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities-conventional intramuscular delivery and percutaneous delivery by scarification-impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.",
keywords = "antibody responses, DNA vaccine, Gag-Pol-Nef, gp140, human immunodeficiency virus, nonhuman primates, NYVAC, NYVAC-KC, T cell responses, vaccine",
author = "Benedikt Asbach and Karen Kibler and Josef K{\"o}stler and Beatriz Perdiguero and Yates, {Nicole L.} and Sherry Stanfield-Oakley and Tomaras, {Georgia D.} and Kao, {Shing Fen} and Foulds, {Kathryn E.} and Mario Roederer and Seaman, {Michael S.} and Montefiori, {David C.} and Robert Parks and Guido Ferrari and Forthal, {Donald N.} and Sanjay Phogat and James Tartaglia and Barnett, {Susan W.} and Self, {Steven G.} and Raphael Gottardo and Cristillo, {Anthony D.} and Weiss, {Deborah E.} and Lindsey Galmin and Song Ding and Heeney, {Jonathan L.} and Mariano Esteban and Bertram Jacobs and Giuseppe Pantaleo and Ralf Wagner",
year = "2019",
month = "2",
day = "1",
doi = "10.1128/JVI.01529-18",
language = "English (US)",
volume = "93",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Priming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein Boost

AU - Asbach, Benedikt

AU - Kibler, Karen

AU - Köstler, Josef

AU - Perdiguero, Beatriz

AU - Yates, Nicole L.

AU - Stanfield-Oakley, Sherry

AU - Tomaras, Georgia D.

AU - Kao, Shing Fen

AU - Foulds, Kathryn E.

AU - Roederer, Mario

AU - Seaman, Michael S.

AU - Montefiori, David C.

AU - Parks, Robert

AU - Ferrari, Guido

AU - Forthal, Donald N.

AU - Phogat, Sanjay

AU - Tartaglia, James

AU - Barnett, Susan W.

AU - Self, Steven G.

AU - Gottardo, Raphael

AU - Cristillo, Anthony D.

AU - Weiss, Deborah E.

AU - Galmin, Lindsey

AU - Ding, Song

AU - Heeney, Jonathan L.

AU - Esteban, Mariano

AU - Jacobs, Bertram

AU - Pantaleo, Giuseppe

AU - Wagner, Ralf

PY - 2019/2/1

Y1 - 2019/2/1

N2 - The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens.IMPORTANCE The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities-conventional intramuscular delivery and percutaneous delivery by scarification-impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.

AB - The use of heterologous immunization regimens and improved vector systems has led to increases in immunogenicity of HIV-1 vaccine candidates in nonhuman primates. In order to resolve interrelations between different delivery modalities, three different poxvirus boost regimens were compared. Three groups of rhesus macaques were each primed with the same DNA vaccine encoding Gag, Pol, Nef, and gp140. The groups were then boosted with either the vaccinia virus strain NYVAC or a variant with improved replication competence in human cells, termed NYVAC-KC. The latter was administered either by scarification or intramuscularly. Finally, macaques were boosted with adjuvanted gp120 protein to enhance humoral responses. The regimen elicited very potent CD4+ and CD8+ T cell responses in a well-balanced manner, peaking 2 weeks after the boost. T cells were broadly reactive and polyfunctional. All animals exhibited antigen-specific humoral responses already after the poxvirus boost, which further increased following protein administration. Polyclonal reactivity of IgG antibodies was highest against HIV-1 clade C Env proteins, with considerable cross-reactivity to other clades. Substantial effector functional activities (antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated virus inhibition) were observed in serum obtained after the last protein boost. Notably, major differences between the groups were absent, indicating that the potent priming induced by the DNA vaccine initially framed the immune responses in such a way that the subsequent boosts with NYVAC and protein led only to an increase in the response magnitudes without skewing the quality. This study highlights the importance of selecting the best combination of vector systems in heterologous prime-boost vaccination regimens.IMPORTANCE The evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The present study evaluated a DNA prime and poxvirus and protein boost regimen and compared how two poxvirus vectors with various degrees of replication capacity and two different delivery modalities-conventional intramuscular delivery and percutaneous delivery by scarification-impact several immune effectors. It was found that despite the different poxvirus boosts, the overall immune responses in the three groups were similar, suggesting the potent DNA priming as the major determining factor of immune responses. These findings emphasize the importance of selecting optimal priming agents in heterologous prime-boost vaccination settings.

KW - antibody responses

KW - DNA vaccine

KW - Gag-Pol-Nef

KW - gp140

KW - human immunodeficiency virus

KW - nonhuman primates

KW - NYVAC

KW - NYVAC-KC

KW - T cell responses

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85060158328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060158328&partnerID=8YFLogxK

U2 - 10.1128/JVI.01529-18

DO - 10.1128/JVI.01529-18

M3 - Article

VL - 93

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -