Serum IgG response to Cryptosporidium immunodominant antigen gp15 and polymorphic antigen gp40 in children with cryptosporidiosis in South India

Abstract

The surface-associated glycopeptides gp40, one of the most polymorphic Cryptosporidium antigens, and gp15, one of the most immunodominant Cryptosporidium antigens, are putative vaccine candidates because they mediate infection in vitro and induce immune responses in vivo. We evaluated antibody responses to these antigens before and after the first episode of symptomatic cryptosporidiosis in 51 children from a birth cohort study in an area in South India where Cryptosporidium is endemic and a major cause of parasitic diarrhea. IgG levels to gp15 and to homotypic and heterotypic gp40 antigens were measured in pre- and postdiarrheal sera by enzyme-linked immunosorbent assay (ELISA). There was a significant IgG response to gp15 (P < 0.001) following the first episode of cryptosporidial diarrhea. Using a general additive model, we determined the estimated time of the peak IgG response to gp15 to be 9.3 weeks (confidence interval, 5.2 to 13.4) following the diarrheal episode. In a subset of 30 children infected with Cryptosporidium hominis subtype Ia, there was a significant difference in IgG responses to homotypic C. hominis Ia and to heterotypic Cryptosporidium parvum II gp40 antigens (P = 0.035). However, there was also a significant correlation (P = 0.001) in the responses to both antigens in individual children, suggesting that while responses are in part subtype specific, there is significant cross-reactivity to both antigens. This is the first report of the characterization of immune responses to cryptosporidiosis in Indian children and the first study to investigate human immune responses to the polymorphic gp40 antigen. However, further studies are needed to determine whether immune responses to these antigens are protective against subsequent infections.