An oral prime/boost pediatric vaccine strategy for the prevention of mother-to-child transmission of HIV by breast-feeding

Abstract

Abstract In 2014, an estimated 220,000 children became newly HIV-infected, with 50% being transmitted via breast-feeding. The present study assessed whether inclusion of an oral route of immunization would increase pediatric vaccine efficacy in the rhesus macaque model of oral SIV infection. Two groups of 6 neonatal macaques received 2 DNA-SIV immunizations at weeks 0 and 3, followed by 2 boosts with modified vaccinia Ankara virus (MVA)-SIVgag/pol/env at weeks 6 and 9. Group A was immunized by the intramuscular (IM) route. Infants in Group B received the DNA-prime both per-orally (PO) and IM and MVA-SIV was administered both by the sublingual (SL) and IM route. Mock control animals received saline immunizations PO+IM at weeks 0 and 3 and mock MVA vector SL+IM at weeks 6 and 9. At week 12, all infants were challenged once weekly using a low-dose (102 TCID50) oral SIVmac251 challenge regimen until systemic infection was confirmed by PCR. Statistical significance was determined using nonparametric Mann-Whitney or Kruskal-Wallis tests with p<0.05. Infants vaccinated by the SL/IM route had a significantly lower per-exposure risk of oral SIV infection (p<0.0001; log-ranked Mantel-Cox test) compared to mock- and IM/IM-vaccinated animals and lower peak viremia (p=0.03) compared to mock controls. Control of viremia was associated with higher fecal IgG responses to SIV V1V2 (p=0.0087) and p55 gag (p=0.0087) at the time of oral challenge initiation. In contrast, plasma SIV-specific antibodies did not influence challenge outcome. These data indicate that the inclusion of an oral route in a pediatric vaccine to prevent oral SIV infection is superior to an IM only regimen and emphasizes the importance of enhancing mucosal immune responses via local immunization.