Role of Immune Responses against the Envelope and the Core Antigens of Simian Immunodeficiency Virus SIVmne in Protection against Homologous Cloned and Uncloned Virus Challenge in Macaques

Abstract

We previously showed that envelope (gp160)-based vaccines, used in a live recombinant virus priming and subunit protein boosting regimen, protected macaques against intravenous and intrarectal challenges with the homologous simian immunodeficiency virus SIVmne clone E11S. However, the breadth of protection appears to be limited, since the vaccines were only partially effective against intravenous challenge by the uncloned SIVmne. To examine factors that could affect the breadth and the efficacy of this immunization approach, we studied (i) the effect of priming by recombinant vaccinia virus; (ii) the role of surface antigen gp130; and (iii) the role of core antigens (Gag and Pol) in eliciting protective immunity. Results indicate that (i) priming with recombinant vaccinia virus was more effective than subunit antigen in eliciting protective responses; (ii) while both gp130 and gp160 elicited similar levels of SIV-specific antibodies, gp130 was not as effective as gp160 in protection, indicating a possible role for the transmembrane protein in presenting functionally important epitopes; and (iii) although animals immunized with core antigens failed to generate any neutralizing antibody and were infected upon challenge, their virus load was 50- to 100-fold lower than that of the controls, suggesting the importance of cellular immunity or other core-specific immune responses in controlling acute infection. Complete protection against intravenous infection by the pathogenic uncloned SIVmne was achieved by immunization with both the envelope and the core antigens. These results indicate that immune responses to both antigens may contribute to protection and thus argue for the inclusion of multiple antigens in recombinant vaccine designs.

Immunogenicity and protective efficacy of Gag/Pol/Env vaccines derived from temporal isolates of SIVmne against cognate virus challenge

“…Our observation that CL8 vaccines protected against homologous CL8 challenge is consistent with our previous findings [13,[31][32][33], although different challenge viruses and animal species were used (molecular clone and pig-tailed macaques in the current study vs. biological clone E11S and cynomolgus macaques in previous ones). Also in line with our previous observation [31,32] is the finding that CL8 vaccines failed to protect against a highly virulent virus 170. However, protective efficacy of the CL8 vaccines was not restricted to the minimally pathogenic homologous virus, as protection and substantial reduction of viral load was achieved in CL8-immunized macaques challenged by the 170/8 chimera, infection by which resulted in high and persistent viremia accompanied by progressive and irreversible CD4 + T cells loss.…”

DNA prime/protein boost vaccine strategy in neonatal macaques against simian human immunodeficiency virus

“…For the most part, a direct comparison to most of these studies is not possible as a result of numerous dierences in experimental protocols. Dierences include animal age, mode of DNA inoculation, use of plasmid vectors or vaccinia virus for priming inoculation, choice of boosting components, challenge routes, and virus strains [26,32,43,46]. However, one study that closely approximated ours in both design and immunizing reagents was completed recently in juvenile macaques [51].…”

Enhanced replication of HIV‐1 in vivo in pigtailed macaques (Macaca nemestrina)

“…A challenge model using SHIV infection of macaques now allows for the testing of vaccines that are aimed at inducing a response against HIV-1 envelope glycoproteins. In such a system, however, testing of HIV-1 gag or pol components is not possible, and experiments using SIV have suggested that immune responses against these viral proteins are important in achieving protection [25]. These developments again underline the need for an animal model that uses HIV-1 rather than SIV or SHIV.…”