h Cholera caused by Vibrio cholerae O1 confers at least 3 to 10 years of protection against subsequent disease regardless of age, despite a relatively rapid fall in antibody levels in peripheral blood, suggesting that memory B cell responses may play an important role in protection. The V. cholerae O1-specific polysaccharide (OSP) component of lipopolysaccharide (LPS) is responsible for serogroup specificity, and it is unclear if young children are capable of developing memory B cell responses against OSP, a T cell-independent antigen, following cholera. To address this, we assessed OSP-specific memory B cell responses in young children (2 to 5 years, n ؍ 11), older children (6 to 17 years, n ؍ 21), and adults (18 to 55 years, n ؍ 28) with cholera caused by V. cholerae O1 in Dhaka, Bangladesh. We also assessed memory B cell responses against LPS and vibriocidal responses, and plasma antibody responses against OSP, LPS, and cholera toxin B subunit (CtxB; a T cell-dependent antigen) on days 2 and 7, as well as days 30, 90, and 180 after convalescence. In all age cohorts, vibriocidal responses and plasma OSP, LPS, and CtxB-specific responses peaked on day 7 and fell toward baseline over the follow-up period. In comparison, we were able to detect OSP memory B cell responses in all age cohorts of patients with detectable responses over baseline for 90 to 180 days. Our results suggest that OSP-specific memory B cell responses can occur following cholera, even in the youngest children, and may explain in part the age-independent induction of long-term immunity following naturally acquired disease. C holera is a severe diarrheal disease that is endemic in 50 countries and associated with recurrent outbreaks and epidemics, especially in resource-limited settings (1). Vibrio cholerae can be classified into approximately 200 serogroups, and epidemic cholera can be caused by V. cholerae O1 and O139 serogroups (1, 2). V. cholerae O1 organisms can be biochemically typed into classical and El Tor biotypes. The O1 serogroup consists of Ogawa and Inaba serotypes, depending, respectively, on the presence or absence of a 2-O-methyl group in the nonreducing (upstream) terminal sugar of the O-specific polysaccharide (OSP) component of the lipopolysaccharide (LPS) (3, 4). Protection against cholera is serogroup specific, with serogroup specificity being determined by the OSP component of LPS (5-10). Previous infection with V. cholerae O1 provides no protection against cholera caused by V. cholerae O139 and vice versa (9,11,12). Ogawa and Inaba serotypes frequently fluctuate during cholera outbreaks, switching most commonly from Ogawa to Inaba (13). Immune responses against Inaba and Ogawa OSP cross-react, with higher immune responses targeting the homologous infecting serotype. Currently, a hybrid strain of V. cholerae O1 El Tor expressing classical cholera toxin (CT) predominates globally (14,15).Children under 5 years of age in regions where cholera is endemic have the highest burden of disease (16,17), although both children...