| Literature DB >> 30429340 |
Karen V Kibler1, Benedikt Asbach2, Beatriz Perdiguero3, Juan García-Arriaza3, Nicole L Yates4, Robert Parks4, Sherry Stanfield-Oakley4, Guido Ferrari4, David C Montefiori4, Georgia D Tomaras4, Mario Roederer5, Kathryn E Foulds5, Donald N Forthal6, Michael S Seaman7, Steve Self8, Raphael Gottardo8, Sanjay Phogat9, James Tartaglia9, Susan Barnett10, Anthony D Cristillo11, Deborah Weiss11, Lindsey Galmin11, Song Ding12, Jonathan L Heeney13, Mariano Esteban3, Ralf Wagner2,14, Giuseppe Pantaleo15, Bertram L Jacobs16,17.
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.Entities:
Keywords: Gag-Pol-Nef; HIV; NYVAC; NYVAC-KC; T cell response; antibody responses; gp140; nonhuman primates; vaccines
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Year: 2019 PMID： 30429340 PMCID： PMC6340019 DOI： 10.1128/JVI.01513-18
Source DB: PubMed Journal: J Virol ISSN： 0022-538X Impact factor: 5.103