J Virol. 2019 Feb 1; 93(3):NA.

PubMed ID: 30429340

Replication-competent NYVAC-KC yields improved immunogenicity to HIV-1 antigens in Rhesus Macaques compared to nonreplicating NYVAC

Kibler KV, Asbach B, Perdiguero B, Garcia-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 BL

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.