Prolonged survival of vaccinated macaques after oral SIVmac239 challenge regardless of viremia control in the chronic phase

Abstract

To evaluate the efficacy of a multigenic vaccine and its protective immunity in the SIVmac239 challenge model, 12 rhesus macaques were divided into two groups. The vaccine group was intramuscularly immunized with multigenic DNA and recombinant adenovirus vaccine, while the control group received buffers. At 16 weeks after the laSt immunization, all macaques were challenged orally with pathogenic SIVmac239. The mean plasma SIV RNA loads of the vaccine group were significantly lower than those of the placebo control group LIP to 16 weeks post-challenge. The vaccine-induced Gag-specific IFN-gamma ELISPOT T cell responses inversely correlated with the viral loads before the chronic phase. Two out of six vaccinated macaques with strong and sustained Gag-specific T cell responses showed viremia control and maintained CD4(+) T cell percentage. However, the other four vaccinated macaques showed high viral loads and reduced level of CD4(+) T cell percentages during the chronic phase, comparable to those in control macaques. Five Out of six vaccinated macaques Survived for more than 72 weeks, while five out of six controls died of an AIDS-related disease. Therefore, the vaccination conferred not only reduction of viral loads in a portion of vaccinated macaques (2/6), but also prolonged survival of all vaccinated macaques regardless of viremia control, Our results further suggest that new experimental approaches may be needed to assess protective effects from AIDS-associated disease in the immunized macaques after oral SIV challenge. (C) 2008 Published by Elsevier Ltd.