MUCOSAL IMMUNITY INDUCED BY PARENTERAL IMMUNIZATION WITH A LIVE ATTENUATED VENEZUELAN EQUINE ENCEPHALITIS-VIRUS VACCINE CANDIDATE

Induction of a mucosal immune response is generally thought to require introduction of an immunogen directly onto the mucosal surface. It ha s been observed, however, that live, attenuated mutants of the alphavi rus, Venezuelan equine encephalitis virus (VEE), induce protection fro m virulent challenge at the respiratory mucosa even after parenteral i noculation. In this report, we propose a mechanism by which subcutaneo us immunization with a molecularly cloned, attenuated double mutant of VEE is able to stimulate the production of mucosal anti-VEE IgA. Our results showed that the immunizing virus spread to, and replicated wit hin, lymphoid tissues throughout the mouse. Several tissues known to b e inductive sites of the mucosal immune system were found to be positi ve for the presence of VEE RNA by 48 hr postimmunization. Moreover, th is mucosal lymphotropism resulted in the production of virus-specific IgA antibody detectable in vaginal secretions of immunized mice. (C) 1 997 Academic Press.