T‐cell‐mediated protective efficacy of a systemic vaccine approach in cynomolgus monkeys after SIV mucosal challenge

Abstract

The immunogenicity and the protective efficacy of a new polyvalent triple vector (DNA/SFV/MVA) based vaccine against mucosal challenge with pathogenic SIVmac251 were investigated. Cynomolgus monkeys (Macaca fascicularis) were primed intradermally with DNA, boosted twice subcutaneously with recombinant Semliki Forest virus (rSFV) and finally intramuscularly with recombinant Modified Vaccinia Virus Ankara strain (rMVA). Both DNA and recombinant viral vectors expressed SIV proteins (Gag, Pol, Tat, Rev, Nef and Env). The vaccinated monkeys developed T helper proliferative responses to viral antigens after the second immunization while interferon (IFN)-gamma enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) specific responses appeared only after the last boost with rMVA. Upon intrarectal challenge with pathogenic SIVmac251, three of four vaccinated monkeys were either fully protected or exhibited a dramatic reduction of virus replication up to undetectable level. A major contribution to this protective effect appeared to be the anamnestic T-cell IFN-gamma ELISPOT responses to vaccine antigens (Gag, Rev, Tat, Nef) that mirrored the viral clearance. These results underline the efficacy of a multiprotein approach in combination with a triple vector system of antigen delivery.

Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques

“…Previous work has shown that Cynomolgus macaques generally (65,66), and Mauritian origin Cynomolgus macaques in particular (67)(68)(69), can be infected with pathogenic SIV and develop sAIDS. When compared with Indian Rhesus macaques, Cynomolgus macaques require a higher dose of virus to consistently establish SIV infection (68) and maintain lower viral loads more similar to HIV-infected humans (66).…”

Lentiviral Vector-Based Prime/Boost Vaccination against AIDS: Pilot Study Shows Protection against Simian Immunodeficiency Virus SIVmac251 Challenge in Macaques

“…Cynomolgus macaques are used for preclinical vaccine evaluation. Various vector strategies have been tested, including DNA, recombinant Semliki Forest and modified recombinant vaccinia virus strain Ankara (MVA) (33,39,40). It is not known whether cynomolgus macaques are easier or not to protect in a vaccination protocol against simian AIDS than Indian rhesus monkeys.…”

Biochemical and Immunogenic Characterization of Soluble Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Expressed by Semliki Forest Virus

“…This system allows the packaging of suicidal, singleround infectious viral particles (23) that have been shown to stimulate protective immunity in a number of different infection models (2,13,34,35). The potential of rSFV as a valuable component of a vaccine against HIV-1 has also been demonstrated, but these studies have primarily focused on the ability of rSFV to stimulate CD8 ϩ T-cell responses (21,33,37). Here, we have characterized the ability of recombinant Semliki Forest virus (rSFV) particles to express soluble YU2gp140 (-/GCN4) trimers in vitro and compared their expression to monomeric YU2gp120 proteins expressed by rSFV.…”