A novel combination vaccine for HIV-1 and tuberculosis is safe and immunogenic in infant rhesus macaques (53.25)

Abstract

Despite improved therapies, breast milk transmission of HIV to newborns does not decline. In many resource-poor countries, these infants are also at risk for Mycobacterium tuberculosis infection. We hypothesized that a highly attenuated Mtb with improved safety and similar immunogenicity to the current BCG vaccine, but modified to harbor HIV genes, could protect infants against both HIV and Tb. We have tested 3 different rAMtb-SIV vectors in infant rhesus macaques. Vaccine safety was evaluated by immunizing 1-week old SIV-infected macaques orally (PO) and intradermally (ID) with rAMtb. Next, we tested the immunogenicity of (1) a PO prime/ID boost rAMtb-SIV, (2) a PO rAMtb-SIV prime/IM Ad5-SIV boost, and (3) an ID rAMtb-SIV prime/IM Ad5-SIV boost vaccine regimen. Our studies show that rAMtb-SIV does not cause rAMtb dissemination, even when given to immunocompromised SIV infected infants. Further, our data confirm that the oral route of immunization is effective in infant macaques. Vaccinated animals showed increased dendritic cell responsiveness to in vitro TLR stimulation, supporting our hypothesis that rAMtb is highly immunogenic in infants. While all vaccine regimens elicited cellular and humoral Mtb-specific immune responses, SIV-specific responses were greatly enhanced by the heterologous boost. Thus, rAMtb-HIV should be further developed as a pediatric combination vaccine. We will test vaccine efficacy against multiple oral SIV challenges and against Mtb exposure.