A rice-based oral cholera vaccine induces macaque-specific systemic neutralizing Abs but does not influence natural intestinal immunity (46.4)

Abstract

We previously showed that oral immunization of mice with a rice-based vaccine expressing cholera toxin (CT) B subunit (MucoRice-CT-B) induced CT-specific immune responses with toxin-neutralizing activity in both systemic and mucosal compartments. Here, we examined whether the rice-based vaccine can induce CT-specific Ab responses in nonhuman primates. Orally administered MucoRice-CT-B induced high levels of CT-neutralizing serum IgG Abs in the 3 cynomolgus macaques we immunized. Although the Ab level gradually decreased, detectable levels were maintained for at least 6 months, and high titers were rapidly recovered after an oral booster dose of the rice-based vaccine. In contrast, no serum IgE Abs against rice storage protein were induced even after multiple immunizations. Interestingly, the macaques harbored naturally acquired intestinal secretory IgA (SIgA) Abs that were capable of reacting with CT and homologous heat-labile enterotoxin (LT) produced by enterotoxigenic E. coli (ETEC) and that had toxin-neutralizing activity. The SIgA Abs were present in macaques 1 month to 29 years old, and the level was not enhanced after oral vaccination with MucoRice-CT-B or after subsequent exposure to the native form of CT. These results show that oral MucoRice-CT-B can effectively induce CT-specific, neutralizing, serum IgG Ab responses even in the presence of pre-existing, naturally occurring CT- and LT-reactive SIgA Abs in nonhuman primates.