Mucosal immunization of cynomolgus macaques with two serotypes of live poliovirus vectors expressing simian immunodeficiency virus antigens: Stimulation of humoral, mucosal, and cellular immunity

Poliovirus live virus vectors are a candidate recombinant vaccine system. P revious studies using this system showed that a live poliovirus vector expr essing a foreign antigen between the structural and nonstructural proteins generates both antibody and cytotoxic T-lymphocyte responses in mice. Here we describe a novel in vitro method of cloning recombinant polioviruses inv olving a hybrid-PCR approach. We report the construction of recombinant vec tors of two different serotypes of poliovirus-expressing simian immunodefic iency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17(gag) and gp41(env). All macaques generated a mucosal a nti-SIV immunoglobulin A (IgA) response in rectal secretions. Two of the fo ur macaques generated mucosal antibody responses detectable in vaginal lava ges. Strong serum IgG responses lasting for at least 1 year were detected i n two of the four monkeys. SIV-specific T-cell lymphoproliferative response s were detected in three of the four monkeys. SIV-specific cytotoxic T lymp hocytes were detected in two of the four monkeys. This is the first report of poliovirus-elicited vaginal IgA or cytotoxic T lymphocytes in any natura lly infectable primate, including humans. These findings support the concep t that a live poliovirus vector is a potentially useful delivery system tha t elicits humoral, mucosal, and cellular immune responses against exogenous antigens.