Comparison of Systemic and Mucosal Synchronous Immunization with Replicating Single-cycle Adenoviruses and SOSIP Protein HIV-1 Vaccines.

Most HIV-1 infections occur at mucosal surfaces. A small number or single incoming virions start each infection and then these amplify exponentially, spread through mucosal tissues and then throughout the body. It is appealing to attempt to stop the infection during those first mucosal infection events when there are fewer viruses to combat. Most vaccines are injected intramuscularly (IM) to drive systemic and mucosal responses. However, data suggests that immunization at mucosal surfaces can build better mucosal barriers than systemic immunization. To explore this question, we performed synchronous immunizations of rhesus macaques with gene-based replicating single-cycle adenovirus (SC-Ad) expressing SIV gag and clade C gp160 envelope, and SOSIP clade C envelope protein vaccine. SOSIP vaccine was delivered by the IM route whereas SC-Ad was delivered by the systemic IM route or by mucosal intranasal (IN) or mucosal intravaginal (IVAG) injections. The same species C Ad6 serotype of SC-Ad was used for all four immunizations by shielding its surface with polyethylene glycol (PEG). 50% of IVAG immunized animals resisted vaginal clade C SHIV 1.5 years after last vaccination. In contrast, IN and IM vaccinated animals were infected with the virus within 10 weeks. These data suggest that vaccination at the mucosal portal of infection provides better localized protection against incoming SHIV and perhaps HIV-1 than standard intramuscular vaccination against repeated mucosal exposure to primate lentiviruses.