Vaccine protection against rectal acquisition of SIVmac239 in rhesus macaques
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
doi:
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:
Cytotoxic T cells – Enzyme-linked immunoassays – Immune response – Rectum – T cells – Vaccination and immunization – Vaccines – SIV
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