Cholera remains a major public health problem in resource-limited countries. Vaccination is an important strategy to prevent
cholera, but currently available
vaccines provide only 3 to 5 years of protection. Understanding immune responses to
cholera antigens in naturally infected individuals may elucidate which of these are key to longer-term protection seen following
infection. We recently identified Vibrio cholerae O1
sialidase, a
neuraminidase that facilitates binding of
cholera toxin to intestinal epithelial cells, as immunogenic following
infection in two recent high-throughput screens. Here, we present systemic, mucosal, and memory immune responses to
sialidase in
cholera index cases and evaluated whether systemic responses to
sialidase correlated with protection using a cohort of household contacts. Overall, we found age-related differences in antisialidase immune response following
cholera. Adults developed significant plasma anti-
sialidase IgA,
IgG, and
IgM responses following
infection, whereas older children (≥5 years) developed both
IgG and
IgM responses, and younger children only developed
IgM responses. Neither older children nor younger children had a rise in
IgA responses over the convalescent phase of
infection (day 7/day 30). On evaluation of mucosal responses and memory B-cell responses to
sialidase, we found adults developed
IgA antibody-secreting cell (ASC) and memory B-cell responses. Finally, in household contacts, the presence of serum anti-
sialidase IgA,
IgG, and
IgM antibodies at enrollment was associated with a decrease in the risk of subsequent
infection. These data show
cholera patients develop age-related immune responses against
sialidase and suggest that immune responses that target
sialidase may contribute to protective immunity against
cholera.IMPORTANCE
Cholera infection can result in severe
dehydration that may lead to death within a short period of time if not treated immediately. Vaccination is an important strategy to prevent the disease. Oral
cholera vaccines provide 3 to 5 years of protection, with 60% protective efficacy, while natural
infection provides longer-term protection than vaccination. Understanding the immune responses after natural
infection is important to better understand immune responses to
antigens that mediate longer-term protection.
Sialidase is a
neuraminidase that facilitates binding of
cholera toxin to intestinal epithelial cells. We show here that patients with
cholera develop systemic, mucosal, and memory B-cell immune responses to the
sialidase antigen of Vibrio cholerae O1 and that plasma responses targeting this
antigen correlate with protection.