UNAIDS estimates that there are 35-40 million people infected with HIV. Heterosexual transmission of HIV continues to spread this epidemic to an estimated 3-4 million people a year. In addition, the growing number of HIV-infected women of child-bearing age results in HIV transmission to over 1,500 infants and children each day. A vaccine capable of preventing HIV transmission offers the best hope of stopping the epidemic. The most important means of eliminating pediatric HIV infection is to prevent women from becoming HIV-infected before or during pregnancy. However, there is little information regarding the efficacy of vaccines to prevent vaginal HIV transmission in pregnant women or HIV transmission from mother to infant. The SIV/cynomolgus macaque model has been recently used to demonstrate that a vaccine consisting of live, recombinant Sabin polio expressing multiple SIV antigens is immunogenic and can elicit protection against vaginal challenge with pathogenic SIV. This proposed project will evaluate the immunogeneicity of an infectious polio-SIV RNA vaccine in adult female cynomolgus macaques before, during and after pregnancy. In addition, this project will determine the immunogeneicity of the same polio-SIV RNA vaccine in the newborns of vaccinated female macaques. These studies will determine whether an infectious viral RNA vaccine is safe and immunogenic during pregnancy and in newborns. Because changes that can affect vaccine-elicited immune responses occur during pregancy, pregnant macaques must be used. In addition, maternal vaccine antigen-specific immunoglobulin that is transplacentally transferred to a fetus can modulate the infant's specific immune responses to later immunization wth the same vaccine antigens. Overall goals of the proposed project: Elicit durable, high levels of SIV-specific immune responses in blood and mucosal fluids (vaginal, rectal and oral) of cynomolgus macaques by inoculation with multiple naked, infectious Sabin-SIV RNAs. A.
Specific Aims : Evaluate immunogenicity and genetic stability of multiple infectious Sabin-SIV RNAs after inoculation in: 1) mice transgenic for the polio virus receptor (PVR) and, 2) cynomolgus macaques, (a) adult females before, during and after pregnancy (b) infants with maternally acquired Sabin-SIV antibodies (infants of vaccinated females).
