(A) Gilchrist and Campo, et al. (18) profiled antibody responses in children previously infected by Cryptosporidium. The authors took serum from children at one year old and measured IgG and IgA against an array of proteins with signal peptide and/or transmembrane domains that correspond with Cryptosporidium extracellular parasite stages: gametocyte, sporozoite, merozoite, oocyst. (B) Cryptosporidium infection occurs after ingestion of infectious oocysts in contaminated water. Oocysts hatch in the small intestinal lumen to release four motile sporozoites that invade the apical side of intestinal epithelial cells (IECs). After invasion, sporozoites develop into intracellular trophozoites, which divide into eight merozoites that can exit the host cell and invade neighboring cells to establish a new infection. Merozoites can also develop into a trophozoite in new cells, thus undergoing asexual replication. After three rounds of asexual replication, parasites develop into male or female forms. Males exit the host cell and fertilization of a female gamete in another cell in the same host results in the formation of a zygote that can divide into four sporozoites to establish a new oocyst. New oocysts released in the feces can infect new hosts or hatch within the same host to autoinfect. Antibodies against seven proteins, expressed during the extracellular stages of Cryptosporidium’s lifecycle, were associated with protection from reinfection.