Vaccine-induced salivary IgA reduces SIV viremia in neonatal rhesus macaques. (P4501)

Abstract

Abstract Vertical transmission of HIV in breast milk remains a primary route of pediatric infections. While neutralizing antibodies are important for preventing viral entry, the role of mucosal antibodies for virus neutralization is still not well described. Neonates produce less mucosal IgA than adults and are thus more susceptible to oral pathogens. Here we tested whether an oral pediatric SIV vaccine could induce salivary IgA and protect against oral SIV acquisition. Rhesus macaques were immunized orally at birth with a live, attenuated Mycobacterium tuberculosis strain engineered to express SIVgag, pol and env proteins and boosted at 3 and 6 weeks with rMVAgag/pol/env. Starting at week 9, animals were orally challenged using a regimen of low-dose SIVmac251 (5000 TCID50) weekly. Although the vaccine did not prevent infection, vaccinated infants with higher SIV-specific salivary IgA antibodies at the time of challenge had lower peak viremia (p=0.034). A similar inverse correlation was observed between peak viremia and fecal IgA (p=0.0019). Salivary IgA concentrations correlated with fecal IgA (p=0.018) but not with plasma IgA (p=0.911). In fact, both plasma IgA and IgG showed trends towards a positive association with viremia. Thus, mucosal, but not systemic, antibodies efficiently controlled virus replication. Vaccine strategies that promote the development of mucosal IgA antibodies will likely improve the efficacy of pediatric vaccines to prevent oral HIV acquisition.