Viral escape mutations do not account for non-protection from SIVmac239 challenge in RhCMV/SIV vaccinated rhesus macaques.

Autor:	Bimber BN; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States.; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., Sunshine J; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., McElfresh GW; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Reed JS; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Pathak R; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Bateman KB; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States., Hughes CM; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., Gilbride RM; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., Ford JC; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., Morrow D; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., Lifson JD; AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD, United States., Sacha JB; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States.; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., Hansen SG; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States.; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States., Picker LJ; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States.; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Aug 07; Vol. 15, pp. 1444621. Date of Electronic Publication: 2024 Aug 07 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1444621
Abstrakt:	Simian immunodeficiency virus (SIV) vaccines based upon 68-1 Rhesus Cytomegalovirus (RhCMV) vectors show remarkable protection against pathogenic SIVmac239 challenge. Across multiple independent rhesus macaque (RM) challenge studies, nearly 60% of vaccinated RM show early, complete arrest of SIVmac239 replication after effective challenge, whereas the remainder show progressive infection similar to controls. Here, we performed viral sequencing to determine whether the failure to control viral replication in non-protected RMs is associated with the acquisition of viral escape mutations. While low level viral mutations accumulated in all animals by 28 days-post-challenge, which is after the establishment of viral control in protected animals, the dominant circulating virus in virtually all unprotected RMs was nearly identical to the challenge stock, and there was no difference in mutation patterns between this cohort and unvaccinated controls. These data definitively demonstrate that viral mutation does not explain lack of viral control in RMs not protected by RhCMV/SIV vaccination. We further demonstrate that during chronic infection RhCMV/SIV vaccinated RMs do not acquire escape mutation in epitopes targeted by RhCMV/SIV, but instead display mutation in canonical MHC-Ia epitopes similar to unvaccinated RMs. This suggests that after the initial failure of viral control, unconventional T cell responses induced by 68-1 RhCMV/SIV vaccination do not exert strong selective pressure on systemically replicating SIV. Competing Interests: Oregon Health & Science University (OHSU), LP, JS, BB, and SH have a substantial financial interest in Vir Biotechnology Inc., a company that may have a commercial interest in the results of this research and technology. LP, and SH have received compensation for consulting for Vir. The potential individual and institutional conflicts of interest have been reviewed and managed by OHSU. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Bimber, Sunshine, McElfresh, Reed, Pathak, Bateman, Hughes, Gilbride, Ford, Morrow, Lifson, Sacha, Hansen and Picker.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu