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Published on: May 6, 2015
Protection against mucosal simian immunodeficiency virus SIV(mac251) challenge by using replicating adenovirus-SIV
L Jean Patterson1, Nina Malkevitch, David Venzon
1Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
Whereas several recent AIDS vaccine strategies have protected rhesus macaques against a pathogenic simian/human immunodeficiency virus (SHIV)(89.6P) challenge, similar approaches have provided only modest, transient reductions in viral burden after challenge with virulent, pathogenic SIV, which is more representative of HIV infection of people. We show here that priming with replicating adenovirus recombinants encoding SIV env/rev, gag, and/or nef genes, followed by boosting with SIV gp120 or an SIV polypeptide mimicking the CD4 binding region of the envelope, protects rhesus macaques from intrarectal infection with the highly pathogenic SIV(mac251). Using trend analysis, significant reductions in acute-phase and set point viremia were correlated with anti-gp120 antibody and cellular immune responses, respectively. Within immunization groups exhibiting significant protection, a subset (39%) of macaques have exhibited either no viremia, cleared viremia, or controlled viremia at the threshold of detection, now more than 40 weeks postchallenge. This combination prime-boost strategy, utilizing replication competent adenovirus, is a promising alternative for HIV vaccine development.
Insights
A novel prime-boost vaccine strategy using adenovirus vectors and SIV components effectively protected macaques against pathogenic SIV infection. This approach shows promise for developing an effective HIV vaccine.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Existing AIDS vaccine strategies show limited efficacy against pathogenic SIV, unlike SHIV.
- Pathogenic SIV infection in macaques better represents human HIV infection.
Purpose of the Study:
- To evaluate a novel prime-boost vaccine strategy for protection against pathogenic SIV.
- To assess the efficacy of adenovirus-based immunization followed by SIV envelope component boosting.
Main Methods:
- Rhesus macaques were primed with replicating adenovirus vectors encoding SIV genes.
- Boost immunization involved SIV gp120 or a CD4 binding region mimic.
- Animals were challenged intrarectally with pathogenic SIV(mac251).
- Viral burden, viremia, and immune responses were monitored.
Main Results:
- The prime-boost strategy significantly protected macaques against SIV(mac251) challenge.
- Reductions in viremia correlated with anti-gp120 antibodies and cellular immunity.
- A subset of vaccinated macaques showed no detectable viremia or cleared it, maintaining control for over 40 weeks.
Conclusions:
- A combination prime-boost strategy using replication-competent adenovirus vectors is a promising approach for HIV vaccine development.
- This strategy induced significant protection and sustained control of pathogenic SIV infection in macaques.
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