Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques

Given the mucosal transmission of HIV-1, we compared whether a mucosal vacc ine could Induce mucosal cytotoxic T lymphocytes (CTLs) and protect rhesus macaques against mucosal infection with simian/human immunodeficiency virus (SHIV) more effectively than the same vaccine given subcutaneously. Here w e show that mucosal CTLs specific for simian immunodeficiency virus can be induced by intrarectal immunization of macaques with a synthetic-peptide va ccine incorporating the LT(R192G) adjuvant. This response correlated with t he level of T-helper response. After intrarectal challenge with pathogenic SHIV-Ku2, viral titers were eliminated more completely (to undetectable lev els) both in blood and intestine, a major reservoir for virus replication, in intrarectally immunized animals than in subcutaneously immunized or cont rol macaques. Moreover, CD4(+) T cells were better preserved. Thus, inducti on of CTLs in the intestinal mucosa, a key site of virus replication, with a mucosal AIDS vaccine ameliorates infection by SHIV in non-human primates.