Oral Coadministration of an Intramuscular DNA/Modified Vaccinia Ankara Vaccine for Simian Immunodeficiency Virus Is Associated with Better Control of Infection in Orally Exposed Infant Macaques

摘要

The majority of human immunodeficiency virus (HIV) type 1 infections in infants are acquired orally through breastfeeding. Toward development of a pediatric HIV vaccine to prevent breastmilk transmission, we tested the efficacy of a simultaneous oral and intramuscular (IM) vaccination regimen for preventing oral simian immunodeficiency virus (SIV) transmission in infant rhesus macaques. Two groups of neonatal macaques were immunized with DNA encoding SIV virus-like particles (DNA-SIV) on weeks 0 and 3, then boosted with modified vaccinia Ankara (MVA) virus expressing SIV antigens (MVA-SIV) on weeks 6 and 9. One group was prime/boosted by the IM route only. Another group was immunized with DNA by both the IM and topical oral (O) buccal routes, and boosted with MVA-SIV by both the IM and sublingual (SL) routes. A third group of control animals received saline by O + IM routes on weeks 0 and 3, and empty MVA by SL + IM routes on weeks 6 and 9. On week 12, infants were orally challenged once weekly with SIV_(mac251) until infected. The vaccine regimen that included oral routes resulted in reduced peak viremia. The rate of infection acquisition in vaccinated infants was found to be associated with prechallenge intestinal immunoglobulin G (IgG) responses to SIV gp120 and V1V2. Peak viremia was inversely correlated with postinfection intestinal IgG responses to gp120, gp41, and V1V2. These results suggest that codelivery of a pediatric HIV vaccine by an oral route may be superior to IM-only regimens for generating mucosal antibodies and preventing HIV breastmilk transmission in neonates.