Cholera is a diarrheal disease caused by
Vibrio cholerae
that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the
V. cholerae
O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to
V. cholerae
and may be a major determinant of long-term protection from cholera. Shanchol, a widely used oral cholera vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype and OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may “prime” the mucosal immune response to vaccine antigens. Our results suggest that the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential vaccine adjuvants is warranted.
Insights into defective serological memory after acute lymphoblastic leukaemia treatment: The role of the plasma cell survival niche, memory B-cells and gut microbiota in vaccine responses