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- Title
Vaccine protection against rectal acquisition of SIVmac239 in rhesus macaques.
- Authors
Gonzalez-Nieto, Lucas; Castro, Isabelle M.; Bischof, Georg F.; Shin, Young C.; Ricciardi, Michael J.; Bailey, Varian K.; Dang, Christine M.; Pedreño-Lopez, Nuria; Magnani, Diogo M.; Ejima, Keisuke; Allison, David B.; Gil, Hwi Min; Evans, David T.; Rakasz, Eva G.; Lifson, Jeffrey D.; Desrosiers, Ronald C.; Martins, Mauricio A.
- Abstract
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.
- Subjects
RHESUS monkeys; GENETIC vectors; SIMIAN immunodeficiency virus; MEDICAL research; HIV; MATERNALLY acquired immunity; CYTOTOXIC T lymphocyte-associated molecule-4
- Publication
PLoS Pathogens, 2019, Vol 15, Issue 9, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1008015