Vibrio cholerae is a bacterial pathogen which causes the severe acute diarrheal disease
cholera. Given that a symptomatic incident of
cholera can lead to long term protection, a thorough understanding of the immune response to this pathogen is needed to identify parameters critical to the generation and durability of immunity. To approach this, we utilized a live attenuated
cholera vaccine to model the response to V. cholerae
infection in 12 naïve subjects. We found that this live
attenuated vaccine induced durable vibriocidal antibody titers that were maintained at least one year after vaccination. Similar to what we previously reported in infected patients from Bangladesh, we found that vaccination induced plasmablast responses were primarily specific to the two
immunodominant antigens lipopolysaccharide (LPS) and
cholera toxin (CT). Interestingly, the magnitude of the early plasmablast response at day 7 predicted the serological outcome of vaccination at day 30. However, this correlation was no longer present at later timepoints. The acute responses displayed preferential
immunoglobulin isotype usage, with LPS specific cells being largely
IgM or
IgA producing, while
cholera toxin responses were predominantly
IgG. Finally, CCR9 was highly expressed on
vaccine induced plasmablasts, especially on
IgM and
IgA producing cells, suggesting a role in migration to the gastrointestinal tract. Collectively, these findings demonstrate that the use of a live attenuated
cholera vaccine is an effective tool to examine the primary and long-term immune response following V. cholerae exposure. Additionally, it provides insight into the phenotype and specificity of the cells which likely return to and mediate immunity at the intestinal mucosa. A thorough understanding of these properties both in peripheral blood and in the intestinal mucosae will inform future
vaccine development against both
cholera and other mucosal pathogens. Trial Registration: NCT03251495.