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Título:	Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC
Autor:	Kibler, K.; Asbach, Benedikt; Perdiguero, Beatriz; 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 W.; Cristillo, Anthony D.; Weiss, Deborah E.; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L.; Esteban, Mariano CSIC ORCID ; Wagner, Ralf; Pantaleo, Giuseppe; Jacobs, Bertram L.
Palabras clave:	Gag-Pol-Nef HIV NYVAC NYVAC-KC T cell response Antibody responses Gp140 Nonhuman primates Vaccines
Fecha de publicación:	feb-2019
Editor:	American Society for Microbiology
Citación:	Journal of Virology 93(3): e01513-18 (2019)
Resumen:	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.
Descripción:	© 2019 Kibler et al.
Versión del editor:	http://dx.doi.org/10.1128/JVI.01513-18
URI:	http://hdl.handle.net/10261/241113
DOI:	10.1128/JVI.01513-18
Identificadores:	doi: 10.1128/JVI.01513-18 issn: 0022-538X e-issn: 1098-5514
Aparece en las colecciones:	(CNB) Artículos