Mother-to-child-transmission of HIV by breast-feeding remains a major obstacle in the eradication of
HIV infection. Compared to adults, HIV-infected infants have more rapid disease and show higher susceptibility to
co-infections like
tuberculosis (TB). Although the Bacille Calmette-Guérin
vaccine can be administered at birth to protect against TB, BCG can disseminate in HIV-infected infants and increase mortality. Thus, a pediatric combination
vaccine to stop both HIV and TB
infection in infants is urgently needed. Towards the goal of developing a pediatric combination HIV-TB
vaccine to prevent both oral HIV acquisition by breast-feeding and TB
infection, we tested and optimized an immunization regimen using a novel live attenuated Mycobacterium tuberculosis
vaccine engineered to express simian immunodeficiency (SIV)
antigens followed by heterologous MVA-SIV boosting in the infant macaque model. A single oral dose of the attenuated Mtb-
SIV vaccine strain mc26435 during the first week of life was sufficient to induce persistent TB-specific immune responses. SIV-specific immunity was induced at low but comparable magnitudes after oral or intradermal priming, and was enhanced following MVA-SIV boosts. T cell responses were most pronounced in intestinal tissues and oral lymph nodes. Importantly, in addition to plasma SIV-specific
IgG and
IgA antibodies, infant macaques developed mucosal SIV-specific
IgA in saliva and intestinal
IgA and
IgG. While future SIV and Mtb challenge studies will be needed to determine the protective efficacy of the Mtb-SIV / MVA-
SIV vaccine, infants at high risk for oral HIV acquisition by breast-feeding and TB
infection could profoundly benefit from an effective combination
vaccine.