Induction of Positive Cellular and Humoral Immune Responses by a Prime-Boost Vaccine Encoded with Simian Immunodeficiency Virusgag/pol

Abstract

It is believed likely that immune responses are responsible for controlling viral load and infection. In this study, when macaques were primed with plasmid DNA encoding SIV gag and pol genes (SIVgag/pol DNA) and then boosted with replication-deficient vaccinia virus DIs recombinant expressing the same genes (rDIsSIVgag/pol), this prime-boost regimen generated higher levels of Gag-specific CD4+ and CD8+ T cell responses than did either SIVgag/pol DNA or rDIsSIVgag/pol alone. When the macaques were i.v. challenged with pathogenic simian/HIV, the prime-boost group maintained high CD4+ T cell counts and reduced plasma viral loads up to 30 wk after viral challenge, whereas the rDIsSIVgag/pol group showed only a partial attenuation of the viral infection, and the group immunized with SIVgag/pol DNA alone showed none at all. The protection levels were better correlated with the levels of virus-specific T cell responses than the levels of neutralization Ab responses. These results demonstrate that a vaccine regimen that primes with DNA and then boosts with a replication-defective vaccinia virus DIs generates anti-SIV immunity, suggesting that it will be a promising vaccine regimen for HIV-1 vaccine development.

Anti-V3 Humanized Antibody KD-247 Effectively Suppresses Ex Vivo Generation of Human Immunodeficiency Virus Type 1 and Affords Sterile Protection of Monkeys against a Heterologous Simian/Human Immunodeficiency Virus Infection

“…In brief, plasma samples were serially diluted and incubated with 100 TCID 50 s of challenge virus, and M8166 cells were then incubated as previously described (26). The neutralization was expressed as the percent inhibition of simian immunodeficiency virus p27 antigen production in the culture supernatants (38,39). Normal monkey plasma was used as a control.…”

Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys

“…In vivo depletion studies with an anti-CD8 monoclonal antibody demonstrated that CD8 + cells are directly involved in containing simian immunodeficiency virus (SIV) infection in primates [11,12]. As such, the most promising and effective vaccine candidates to date against simian-human immunodeficiency virus (SHIV) challenge of macaques have aimed at inducing strong cellular immune responses [13][14][15][16]. Many vaccine candidates currently in clinical trials are focused on inducing cellular immune responses, especially CD8 + cytotoxic T lymphocyte (CTL) responses [17].…”

Recombinant Vaccinia DIs Expressing Simian Immunodeficiency Virus Gag and Pol in Mammalian Cells Induces Efficient Cellular Immunity as a Safe Immunodeficiency Virus Vaccine Candidate

“…Recombinant MVA-based vaccines are being developed for a variety of diseases including HIV/AIDS (14, 20, 21, 24), and various SIV vaccines utilize prime/boost regimens, including DNA/recombinant MVA with or without IL-2 (2, 5) and DNA/recombinant adenovirus (35,38). A prime/boost regimen with DNA/recombinant DIs has been shown to elicit positive immunity in mice and macaque models (39,41). Furthermore, although rDIsSIVgag/pol was not able to replicate in the mammalian cell lines HeLa and CV-1 cells, it formed small plaques similar to those formed by MVA/SIV239gag/pol.…”

“…Because the vaccinia DIs strain lends itself to recombination, it could also be used as a vector expressing foreign genes (15,41). Recently, the simian immunodeficiency virus (SIV) gag and pol gene-encoded recombinant DIs (rDIsSIVgag/pol) proved effective at eliciting anti-SIV immunity in mice and macaques when administered as a booster antigen after priming with SIV-DNA (39,41) and with rBCGSIVgag (3).…”