Kibler, Karen V. and Asbach, Benedikt and Perdiguero, Beatriz and Garcia-Arriaza, Juan and Yates, Nicole L. and Parks, Robert and Stanfield-Oakley, Sherry and Ferrari, Guido and Montefiori, David C. and Tomaras, Georgia D. and Roederer, Mario and Foulds, Kathryn E. and Forthal, Donald N. and Seaman, Michael S. and Self, Steve and Gottardo, Raphael and Phogat, Sanjay and Tartaglia, James and Barnett, Susan and Cristillo, Anthony D. and Weiss, Deborah and Galmin, Lindsey and Ding, Song and Heeney, Jonathan L. and Esteban, Mariano and Wagner, Ralf and Pantaleo, Giuseppe and Jacobs, Bertram L. (2019) Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC. JOURNAL OF VIROLOGY, 93 (3): e01513-18. ISSN 0022-538X, 1098-5514
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELL RESPONSES; GROUP-M CONSENSUS; PHASE-I TRIAL; VACCINE EFFICACY; DNA PRIME; MEDIATED CYTOTOXICITY; ENVELOPE PROTEIN; ANTIBODIES; VECTORS; BOOST; Gag-Pol-Nef; HIV; NYVAC; NYVAC-KC; T cell response; antibody responses; gp140; nonhuman primates; vaccines |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Apr 2020 09:17 |
| Last Modified: | 22 Apr 2020 09:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27684 |
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