Long-Term Cholera Antitoxin Memory in the Gut can be Triggered to Antibody Formation Associated with Protection within Hours of an Oral Challenge Immunization

A local mucosal immunological memory that could be efficiently triggered to protective antibody formation on renewed antigen exposure might account for the several-year long protection against reinfection and disease seen in individuals after cholera disease. The duration and other functional aspects of gut mucosal immunological memory to the cholera toxin (CT), which is the key pathogenic factor in cholera, were examined in mice. Six months or even 2 years after an initial series of oral immunizations with CT a single repeat oral exposure to CT in submicrogram amounts evoked a brisk IgA antitoxin response in the lamina propria. A three-fold increase in IgA antitoxin-producing cells (SFC) was evident within 16 h, with a further rise in SFC numbers over the next several days. The anamnestic gut mucosal IgA antitoxin response was associated with a substantial increase in protection against challenge of intestinal loops with CT. The rapid increase in IgA antitoxin SFC in the gut is believed to reflect memory cells dispersed in the gut mucosa which can be rapidly triggered into antitoxin formation by antigen encounter in vivo and such cells could clearly be responsible for the long-term immunity seen after cholera disease or oral vaccination.