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. CristilloDeborah Weiss, Lindsey Galmin, Song Ding, Jonathan L. Heeney, Mariano Esteban, Ralf Wagner, Giuseppe Pantaleo, Bertram Jacobs

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Article numbere01513-18
JournalJournal of virology
Volume93
Issue number3
DOIs
StatePublished - Feb 1 2019

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

Fingerprint

Dive into the research topics of 'Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV -1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC'. Together they form a unique fingerprint.

Cite this