Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC

Karen Kibler, Benedikt Asbach, Beatriz Perdiguero, Juan García-Arriaza, Nicole L. Yates, Robert Parks, Sherry Stanfield-Oakley, Guido Ferrari, David C. Montefiori, Georgia D. Tomaras, Mario Roederer, Kathryn E. Foulds, Donald N. Forthal, Michael S. Seaman, Steve Self, Raphael Gottardo, Sanjay Phogat, James Tartaglia, Susan Barnett, Anthony D. Cristillo & 8 others Deborah Weiss, Lindsey Galmin, Song Ding, Jonathan L. Heeney, Mariano Esteban, Ralf Wagner, Giuseppe Pantaleo, Bertram Jacobs

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial.IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.

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

Fingerprint

HIV Antigens
Human immunodeficiency virus 1
Macaca mulatta
HIV-1
Vaccines
immune response
clinical trials
vaccines
antigens
Poxviridae
Phase III Clinical Trials
Primates
Clinical Trials
Viral Envelope Proteins
AIDS Vaccines
Vaccinia virus
vector vaccines
virus-like particles
Recombinant Proteins
Virion

Keywords

  • antibody responses
  • Gag-Pol-Nef
  • gp140
  • HIV
  • nonhuman primates
  • NYVAC
  • NYVAC-KC
  • T cell response
  • vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC. / Kibler, Karen; Asbach, Benedikt; Perdiguero, Beatriz; García-Arriaza, Juan; Yates, Nicole L.; Parks, Robert; Stanfield-Oakley, Sherry; Ferrari, Guido; Montefiori, David C.; Tomaras, Georgia D.; Roederer, Mario; Foulds, Kathryn E.; Forthal, Donald N.; Seaman, Michael S.; Self, Steve; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, James; Barnett, Susan; Cristillo, Anthony D.; Weiss, Deborah; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L.; Esteban, Mariano; Wagner, Ralf; Pantaleo, Giuseppe; Jacobs, Bertram.

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

Research output: Contribution to journalArticle

Kibler, K, Asbach, B, Perdiguero, B, García-Arriaza, J, Yates, NL, Parks, R, Stanfield-Oakley, S, Ferrari, G, Montefiori, DC, Tomaras, GD, Roederer, M, Foulds, KE, Forthal, DN, Seaman, MS, Self, S, Gottardo, R, Phogat, S, Tartaglia, J, Barnett, S, Cristillo, AD, Weiss, D, Galmin, L, Ding, S, Heeney, JL, Esteban, M, Wagner, R, Pantaleo, G & Jacobs, B 2019, 'Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC', Journal of virology, vol. 93, no. 3. https://doi.org/10.1128/JVI.01513-18
Kibler, Karen ; Asbach, Benedikt ; Perdiguero, Beatriz ; García-Arriaza, Juan ; Yates, Nicole L. ; Parks, Robert ; Stanfield-Oakley, Sherry ; Ferrari, Guido ; Montefiori, David C. ; Tomaras, Georgia D. ; Roederer, Mario ; Foulds, Kathryn E. ; Forthal, Donald N. ; Seaman, Michael S. ; Self, Steve ; Gottardo, Raphael ; Phogat, Sanjay ; Tartaglia, James ; Barnett, Susan ; Cristillo, Anthony D. ; Weiss, Deborah ; Galmin, Lindsey ; Ding, Song ; Heeney, Jonathan L. ; Esteban, Mariano ; Wagner, Ralf ; Pantaleo, Giuseppe ; Jacobs, Bertram. / Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC. In: Journal of virology. 2019 ; Vol. 93, No. 3.
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AU - Kibler, Karen

AU - Asbach, Benedikt

AU - Perdiguero, Beatriz

AU - García-Arriaza, Juan

AU - Yates, Nicole L.

AU - Parks, Robert

AU - Stanfield-Oakley, Sherry

AU - Ferrari, Guido

AU - Montefiori, David C.

AU - Tomaras, Georgia D.

AU - Roederer, Mario

AU - Foulds, Kathryn E.

AU - Forthal, Donald N.

AU - Seaman, Michael S.

AU - Self, Steve

AU - Gottardo, Raphael

AU - Phogat, Sanjay

AU - Tartaglia, James

AU - Barnett, Susan

AU - Cristillo, Anthony D.

AU - Weiss, Deborah

AU - Galmin, Lindsey

AU - Ding, Song

AU - Heeney, Jonathan L.

AU - Esteban, Mariano

AU - Wagner, Ralf

AU - Pantaleo, Giuseppe

AU - Jacobs, Bertram

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N2 - As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial.IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.

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KW - Gag-Pol-Nef

KW - gp140

KW - HIV

KW - nonhuman primates

KW - NYVAC

KW - NYVAC-KC

KW - T cell response

KW - vaccines

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