Improved access to antiretroviral
therapy (ART) and
antenatal care has significantly reduced in utero and peripartum mother-to-child human immunodeficiency virus (HIV) transmission. However, as breast milk transmission of HIV still occurs at an unacceptable rate, there remains a need to develop an effective
vaccine for the pediatric population. Previously, we compared different
HIV vaccine strategies, intervals, and adjuvants in infant rhesus macaques to optimize the induction of HIV envelope (Env)-specific
antibodies with Fc-mediated effector function. In this study, we tested the efficacy of an optimized
vaccine regimen against oral simian-human immunodeficiency virus (SHIV) acquisition in infant macaques. Twelve animals were immunized with 1086.c gp120
protein adjuvanted with
3M-052 in stable
emulsion and modified
vaccinia Ankara (MVA) virus expressing 1086.c HIV Env. Twelve control animals were immunized with empty MVA. The
vaccine prime was given within 10 days of birth, with booster doses being administered at weeks 6 and 12. The
vaccine regimen induced Env-specific plasma
IgG antibodies capable of antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Beginning at week 15, infants were exposed orally to escalating doses of heterologous SHIV-1157(QNE)Y173H once a week until infected. Despite the induction of strong Fc-mediated antibody responses, the
vaccine regimen did not reduce the risk of
infection or time to acquisition compared to controls. However, among vaccinated animals, ADCC postvaccination and postinfection was associated with reduced peak
viremia. Thus, nonneutralizing Env-specific
antibodies with Fc effector function elicited by this
vaccine regimen were insufficient for protection against heterologous oral SHIV
infection shortly after the final immunization but may have contributed to control of
viremia. IMPORTANCE Women of childbearing age are three times more likely to contract
HIV infection than their male counterparts. Poor HIV testing rates coupled with low adherence to antiretroviral
therapy (ART) result in a high risk of mother-to-infant HIV transmission, especially during the breastfeeding period. A preventative
vaccine could curb pediatric
HIV infections, reduce potential health sequalae, and prevent the need for lifelong ART in this population. The results of the current study imply that the HIV Env-specific
IgG antibodies elicited by this candidate
vaccine regimen, despite a high magnitude of Fc-mediated effector function but a lack of
neutralizing antibodies and polyfunctional T cell responses, were insufficient to protect infant rhesus macaques against oral virus acquisition.