Protection against Mucosal Simian Immunodeficiency Virus SIV _mac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting

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.

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

“…These replicating vaccines have been shown to elicit better cellular immune responses and prime higher titered antibodies, including functional antibodies, compared to replication-defective Ad-recombinants encoding the same HIV genes [31,32]. When combined with envelope subunit boosting, the vaccine strategy has shown potent protection against virulent SIV mac251 challenge [33] and durable protective efficacy with no intervening boost [34].…”

Chimpanzee-origin adenovirus vectors as vaccine carriers

“…Most of the past efforts focused on human Ads, such as those of the common serotype 5 (AdHu5), which cause mild upper respiratory symptoms upon natural infections. Both replication competent 9,10 and E1-deleted (DE1) replication-defective AdHu5 vectors have been developed as vaccine carriers and have shown efficacy in mice, 11 dogs 12,13 and nonhuman primates (NHPs). 7 E1-deleted AdHu5 vectors also performed well in clinical trials.…”

Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

“…Efforts have been directed at improving these responses by boosting with viral vectors (Amara et al, 2002;Brave et al, 2007;Casimiro et al, 2005;Doria-Rose et al, 2003;Hel et al, 2006;Koopman et al, 2004;Letvin et al, 2004). DNA vaccines are generally effective at stimulating CD8 responses, whilst subunit vaccines are more effective at eliciting antibody responses (Barouch et al, 2000;Earl et al, 2001Earl et al, , 2002Patterson et al, 2004;Robinson, 1999). Combined-modality DNA prime-protein boost vaccination strategies have been evaluated in the past (Cristillo et al, 2006;Letvin et al, 1997;Mooij et al, 2004;Otten et al, 2005;Pal et al, 2005Pal et al, , 2006Robinson et al, 1999).…”