HIV, diarrheal diseases of children and sexually transmitted diseases infect mucosal surfaces and are associated with tremendous morbidity and mortality. Vaccines designed to protect against these pathogens must induce mucosal immune responses. To date, no single immunization strategy has proven to be satisfactory in generating the required immune response in mucosal secretions or tissues. The use of attenuated recombinant mucosal pathogens to deliver antigen to the mucosal immune system is a potentially important method of generating mucosal immunity. Dr. Feinberg's group has used recombinant DNA technology to produce chimeric polioviruses that may be used as vaccines. These viruses provide a method to deliver the appropriate antigens to mucosal surfaces and elicit specific immune responses in the desired anatomic location. We have begun testing the immunogenicity and stability of poliovirus constructs expressing HIV and SIV antigens in rhesus and cynomolgus macaques. These studies have demonstrated that the oral immunization with the recombinant viruses results in infection of cynomolgus macaques but not rhesus macaques. The recombinant viruses are stable in-vivo and the analysis of the immune responses generated by these chimeric is in progress. If this approach results in genital; immune responses to SIV antigens, animals will be challenged vaginally with virulent siv. If this approach proves successful in eliciting mucosal immunity, the studies will be expanded to include vaccination against a variety of mucosal pathogens.
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