Protective Efficacy of an AIDS Vaccine, a Single DNA Priming Followed by a Single Booster with a Recombinant Replication-Defective Sendai Virus Vector, in a Macaque AIDS Model

Abstract

We previously demonstrated the excellent protective efficacy of DNA priming followed by Gag-expressing Sendai virus (SeV) boosting (DNA prime/SeV-Gag boost vaccine) against a pathogenic simian-human immunodeficiency virus (SHIV89.6PD) infection in macaques. Here we show that we established a practical, safer AIDS vaccine protocol, a single DNA priming followed by a single booster with a recently developed replicationdefective F deletion SeV-expressing Gag, and show its protective efficacy against SHIV89.6PD infections.

Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques

“…However, several vaccination protocols have achieved preservation of CD4 + T cells (Amara et al, 2001;Barouch et al, 2000;Doria-Rose et al, 2003;Mooij et al, 2004;Shiver et al, 2002;Takeda et al, 2003;Voss et al, 2003), including the CD4 + memory subsets (Nishimura et al, 2004). A unique opportunity is thus provided to study immune activation and its relationship to the establishment of a set-point virus load in the absence of memory T-cell loss.…”

Viral vectors for use in the development of biodefense vaccines

“…One advantage of using RV as a vector is that it allows for expression of multiple genes and of very large genes (approximately 6.6 kb). Vaccine vectors constructed from two members of the Paramyxoviridae family, Sendai virus and bovine parainfluenza virus type 3, have been effective at inducing protective immune responses against simian-HIV and against respiratory syncytial virus in animals, respectively [109,110]. Because different viruses display different cellular tropisms and can stimulate different types of immune responses, constructing viral vectors based on these different viruses maybe useful in designing new vaccines that can stimulate immune responses most appropriate for a given biological threat agents.…”

Vaccine-based, long-term, stable control of simian/human immunodeficiency virus 89.6PD replication in rhesus macaques

“…In a model of X4-tropic simian/human immunodeficiency virus (SHIV) 89.6P or 89.6PD infection (Reimann et al, 1996;Lu et al, 1998), which causes rapid CD4 + T-cell depletion leading to an acute crash of the host immune system in macaques, several pre-clinical trials of prophylactic AIDS vaccines have successfully shown that efficient CTL induction results in control of virus replication and prevention of acute AIDS progression (Barouch et al, 2000;Amara et al, 2001;Matano et al, 2001;Rose et al, 2001;Shiver et al, 2002;Willey et al, 2003 We have developed a prophylactic AIDS vaccine using a DNA-prime/Gag-expressing Sendai virus (SeV-Gag) vector boost system and have shown its potential for efficient induction of Gag-specific CTL responses in Burmese rhesus macaques (Kano et al, 2002;Matano et al, 2004). In preclinical trials in an acute AIDS model, all of the macaques vaccinated with the DNA-prime/SeV-Gag vector boost system controlled SHIV89.6PD replication after challenge (Matano et al, 2001;Takeda et al, 2003). Furthermore, a trial of the prophylactic DNA-prime/SeV-Gag boost vaccine showed control of SIVmac239 replication leading to undetectable set-point plasma viraemia in five out of eight vaccinees (referred to as SIV controllers), despite failure of virus control in the other three vaccinees (referred to as SIV non-controllers) (Matano et al, 2004).…”

“…In preclinical trials in an acute AIDS model, all of the macaques vaccinated with the DNA-prime/SeV-Gag vector boost system controlled SHIV89.6PD replication after challenge (Matano et al, 2001;Takeda et al, 2003). Furthermore, a trial of the prophylactic DNA-prime/SeV-Gag boost vaccine showed control of SIVmac239 replication leading to undetectable set-point plasma viraemia in five out of eight vaccinees (referred to as SIV controllers), despite failure of virus control in the other three vaccinees (referred to as SIV non-controllers) (Matano et al, 2004).…”

“…et al, 2000). Three macaques (R00-020, R00-023 and R00-024) received a single immunization with CMV-SHIVdEN DNA (DNAv3) followed by a single boost with an F-deleted replication-defective SeV-Gag (F 2 SeV-Gag) (Li et al, 2000;Takeda et al, 2003). This CMV-SHIVdEN plasmid DNA was constructed from an env-and nef-deleted SHIV MD14YE molecular clone DNA and had the genes encoding SIVmac239 Gag, Pol, Vif and Vpx, SIVmac239/HIV-1 DH12 chimeric Vpr and HIV-1 DH12 Tat and Rev (Matano et al, 2004).…”