TY - JOUR
T1 - Vaccine protection against rectal acquisition of SIVmac239 in rhesus macaques
AU - Gonzalez-Nieto, Lucas
AU - Castro, Isabelle M.
AU - Bischof, Georg F.
AU - Shin, Young C.
AU - Ricciardi, Michael J.
AU - Bailey, Varian K.
AU - Dang, Christine M.
AU - Pedreño-Lopez, Nuria
AU - Magnani, Diogo M.
AU - Ejima, Keisuke
AU - Allison, David B.
AU - Gil, Hwi Min
AU - Evans, David T.
AU - Rakasz, Eva G.
AU - Lifson, Jeffrey D.
AU - Desrosiers, Ronald C.
AU - Martins, Mauricio A.
N1 - Funding Information:
This work was funded by Public Health Service (PHS) grant K01 OD023032 (M.A.M.) from the Office of the Director, National Institutes of Health (NIH). Partial support came from PHS grants R37 AI063928 (R.C.D.), R01 AI121135 (D. T.E.), R01 AI095098 (D.T.E.), and R01 AI052056 to David I. Watkins from the National Institute of Allergy and Infectious Diseases. Additional partial support came from federal funds from the National Cancer Institute under Contract HHSN261200800001E (to J.D.L.). We also acknowledge support from the Miami Center for AIDS Research at the University of Miami Miller School of Medicine funded by NIH Grant P30AI073961. Part of this work was performed in a facility supported by NIH grant 5P51OD011106 to the Wisconsin National Primate Research Center at the University of Wisconsin-Madison. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
Copyright © 2019 Gonzalez-Nieto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.ppat.1008015
DO - 10.1371/journal.ppat.1008015
M3 - Article
C2 - 31568531
AN - SCOPUS:85073184664
VL - 15
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 9
M1 - e1008015
ER -