A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified Vaccinia Ankara viral vector-based vaccine induces simian immunodeficiency virus-specific systemic and mucosal immune responses in juvenile rhesus macaques.

BACKGROUND: A pediatric vaccine to prevent breast milk transmission of human immunodeficiency virus (HIV) may generate greater immune responses at viral entry sites if given by an oral route.

METHODS: We compared immune responses induced in juvenile macaques by prime/boosting with simian immunodeficiency virus (SIV)-expressing DNA/modified vaccinia Ankara virus (MVA) by the intramuscular route (IM), the oral (O)/tonsillar routes (T), the O/sublingual (SL) routes, and O+IM/SL routes.

RESULTS: O/T or O/SL immunization generated SIV-specific T cells in mucosal tissues but failed to induce SIV-specific IgA in saliva or stool or IgG in plasma. IM/IM or O+IM/SL generated humoral and cellular responses to SIV. IM/IM generated greater frequencies of TFH in spleen, but O+IM/SL animals had higher avidity plasma IgG and more often demonstrated mucosal IgA responses.

CONCLUSION: These results suggest that codelivery of HIV DNA/MVA vaccines by the oral and IM routes might be optimal for generating both systemic and mucosal antibodies.