Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors

Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vacci ne vector. New poliovirus vectors based on Sabin I and 2 vaccine strain vir uses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragm ents. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SI V were inoculated into seven cynomolgus macaques. All monkeys produced subs tantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotox ic T-lymphocyte responses were detected in three of seven monkeys after vac cination. All 7 vaccinated macaques, as well as 12 control macaques, were c hallenged vaginally with pathogenic SIVmac251. Strikingly, four of the seve n vaccinated animals exhibited substantial protection against the vaginal S IV challenge. All 12 control monkeys became SIV positive. In two of the sev en SabRV-SIV-vaccinated monkeys we found no virological evidence of infecti on following challenge, indicating that these two monkeys were completely p rotected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounce d reduction in postacute viremia to < 10(3) copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six contro l animals developed clinical AIDS by 48 weeks postchallenge. In contrast, a ll seven vaccinated monkeys remained healthy as judged by all clinical para meters. These results demonstrate the efficacy of SabRV as a potential huma n vaccine vector, and they show that the use of a vaccine vector cocktail e xpressing an array of defined antigenic sequences can be an effective vacci nation strategy in an outbred population.