Vaccine protection against rectal acquisition of SIVmac239 in rhesus macaques

English version

Autoři: Lucas Gonzalez-Nieto ^aff001; Isabelle M. Castro ^aff001; Georg F. Bischof ^aff001; Young C. Shin ^aff001; Michael J. Ricciardi ^aff001; Varian K. Bailey ^aff001; Christine M. Dang ^aff001; Nuria Pedreño-Lopez ^aff001; Diogo M. Magnani ^aff001; Keisuke Ejima ^aff002; David B. Allison ^aff002; Hwi Min Gil ^aff003; David T. Evans ^aff003; Eva G. Rakasz ^aff003; Jeffrey D. Lifson ^aff005; Ronald C. Desrosiers ^aff001; Mauricio A. Martins ^aff001
Působiště autorů: Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, United States of America ^aff001; Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, Indiana, United States of America ^aff002; Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, United States of America ^aff003; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America ^aff004; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America ^aff005
Vyšlo v časopise: Vaccine protection against rectal acquisition of SIVmac239 in rhesus macaques. PLoS Pathog 15(9): e32767. doi:10.1371/journal.ppat.1008015
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1008015

Souhrn

A prophylactic vaccine against human immunodeficiency virus (HIV) remains a top priority in biomedical research. Given the failure of conventional immunization protocols to confer robust protection against HIV, new and unconventional approaches may be needed to generate protective anti-HIV immunity. Here we vaccinated rhesus macaques (RMs) with a recombinant (r)DNA prime (without any exogenous adjuvant), followed by a booster with rhesus monkey rhadinovirus (RRV)−a herpesvirus that establishes persistent infection in RMs (Group 1). Both the rDNA and rRRV vectors encoded a near-full-length simian immunodeficiency virus (SIVnfl) genome that assembles noninfectious SIV particles and expresses all nine SIV gene products. This rDNA/rRRV-SIVnfl vaccine regimen induced persistent anti-Env antibodies and CD8+ T-cell responses against the entire SIV proteome. Vaccine efficacy was assessed by repeated, marginal-dose, intrarectal challenges with SIVmac239. Encouragingly, vaccinees in Group 1 acquired SIVmac239 infection at a significantly delayed rate compared to unvaccinated controls (Group 3). In an attempt to improve upon this outcome, a separate group of rDNA/rRRV-SIVnfl-vaccinated RMs (Group 2) was treated with a cytotoxic T-lymphocyte antigen-4 (CTLA-4)-blocking monoclonal antibody during the vaccine phase and then challenged in parallel with Groups 1 and 3. Surprisingly, Group 2 was not significantly protected against SIVmac239 infection. In sum, SIVnfl vaccination can protect RMs against rigorous mucosal challenges with SIVmac239, a feat that until now had only been accomplished by live-attenuated strains of SIV. Further work is needed to identify the minimal requirements for this protection and whether SIVnfl vaccine efficacy can be improved by means other than anti-CTLA-4 adjuvant therapy.

Klíčová slova:

Immune response – Vaccination and immunization – T cells – Cytotoxic T cells – Vaccines – Enzyme-linked immunoassays – Rectum – SIV

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