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.
Highlights
Human immunodeficiency virus (HIV) continues to infect thousands of new people every day, despite advances in prevention modalities and antiretroviral therapy coverage [1]
We investigated whether vaccination with a near-full-length simian immunodeficiency virus (SIVnfl) genome could protect rhesus macaques (RMs) against pathogenic SIV challenge
The sixteen RMs in Groups 1 and 2 were each primed with two rDNA-SIVnfl plasmids that differed only in the Env protein expressed by each plasmid (S1A and S1B Fig)
Summary
Human immunodeficiency virus (HIV) continues to infect thousands of new people every day, despite advances in prevention modalities and antiretroviral therapy coverage [1]. Mathematical models have suggested that combining current HIV prevention and treatment strategies with a prophylactic HIV vaccine could significantly restrict the growth of the HIV pandemic [2]. RRRV-SIVnfl vaccination induced CD8+ T-cell responses against all nine SIV proteins, consistent with the ability of the SIVnfl insert to express the entire SIVnfl proteome [11]. These features are observed following inoculation with live-attenuated SIV strains, the most effective vaccine modality against pathogenic SIV challenge in nonhuman primates
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
