Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC.

Details

Serval ID
serval:BIB_C7AB149CAD1E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC.
Journal
Journal of virology
Author(s)
Kibler K.V., Asbach B., Perdiguero B., García-Arriaza J., Yates N.L., Parks R., Stanfield-Oakley S., Ferrari G., Montefiori D.C., Tomaras G.D., Roederer M., Foulds K.E., Forthal D.N., Seaman M.S., Self S., Gottardo R., Phogat S., Tartaglia J., Barnett S., Cristillo A.D., Weiss D., Galmin L., Ding S., Heeney J.L., Esteban M., Wagner R., Pantaleo G., Jacobs B.L.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Publication state
Published
Issued date
01/02/2019
Peer-reviewed
Oui
Volume
93
Number
3
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
Animals, Antibodies, Neutralizing/blood, CD4-Positive T-Lymphocytes/immunology, HIV Antibodies/blood, HIV Antigens/immunology, HIV Infections/immunology, HIV Infections/prevention & control, HIV Infections/virology, HIV-1/immunology, Humans, Macaca mulatta, Male, Vaccination, Vaccinia virus/immunology, Viral Vaccines/administration & dosage, Viral Vaccines/immunology, Virus Replication, env Gene Products, Human Immunodeficiency Virus/immunology, Gag-Pol-Nef, HIV, NYVAC, NYVAC-KC, T cell response, antibody responses, gp140, nonhuman primates, vaccines
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2018 14:19
Last modification date
16/11/2019 7:16
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