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. 2019 Jan 31;13(1):e0007057.
doi: 10.1371/journal.pntd.0007057. eCollection 2019 Jan.

Bivalent oral cholera vaccination induces a memory B cell response to the V. cholerae O1-polysaccharide antigen in Haitian adults

Brie Falkard  1 , Richelle C Charles  1   2 , Wilfredo R Matias  2   3 , Leslie M Mayo-Smith  1 , J Gregory Jerome  4 , Evan S Offord  1 , Peng Xu  5 , Pavol Kováč  5 , Edward T Ryan  1   2   6 , Firdausi Qadri  7 , Molly F Franke  8 , Louise C Ivers  1   2   4   8   9 , Jason B Harris  1   10   11
Affiliations

Bivalent oral cholera vaccination induces a memory B cell response to the V. cholerae O1-polysaccharide antigen in Haitian adults

Brie Falkard et al. PLoS Negl Trop Dis. .

Abstract

The bivalent killed whole-cell oral cholera vaccine (BivWC) is being increasingly used to prevent cholera. The presence of O-antigen-specific memory B cells (MBC) has been associated with protective immunity against cholera, yet MBC responses have not been evaluated after BivWC vaccination. To address this knowledge gap, we measured V. cholerae O1-antigen MBC responses following BivWC vaccination. Adults in St. Marc, Haiti, received 2 doses of the BivWC vaccine, Shanchol, two weeks apart. Participants were invited to return at days 7, 21, 44, 90, 180 and 360 after the initial vaccination. Serum antibody and MBC responses were assessed at each time-point before and following vaccination. We observed that vaccination with BivWC resulted in significant O-antigen specific MBC responses to both Ogawa and Inaba serotypes that were detected by day 21 and remained significantly elevated over baseline for up to 12 months following vaccination. The BivWC oral cholera vaccine induces durable MBC responses to the V. cholerae O1-antigen. This suggests that long-term protection observed following vaccination with BivWC could be mediated or maintained by MBC responses.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Enrollment, vaccination and follow-up of study participants.
Fig 2
Fig 2. Vibriocidal responses.
Geometric mean titer (±SEM) of vibriocidal responses to V. cholerae O1 Ogawa (A) and Inaba (B). Statistically significant differences relative to baseline (Day 0) are indicated. (* = P<0.05, ** = P<0.01, *** = P<0.001, **** = P<0.0001). Seroconversion for vibriocidal is defined as ≥4-fold increase over baseline. Seroconversion for OSP is defined as ≥2-fold increase in kinetic ELISA. Participants were included if they positively seroconverted by either Day 7 or 21.
Fig 3
Fig 3. OSP-specific responses.
Mean plasma antibody IgG (A), IgA (B) and IgM (C) OSP-specific responses to V. cholerae O1 Ogawa and Inaba. Statistically significant differences relative to baseline (Day 0) are indicated. (* = P<0.05, ** = P<0.01, *** = P<0.001, **** = P<0.0001).
Fig 4
Fig 4. Memory B Cell OSP-specific responses.
Mean antigen-specific IgG (A) and IgA (B) memory B cell responses to Ogawa and Inaba OSP, as percentages of total memory B cells, with error bars representing standard error of the mean. Statistically significant differences relative to baseline (Day 0) are indicated. (* = P<0.05, ** = P<0.01, *** = P<0.001, **** = P<0.0001).
Fig 5
Fig 5. IgM Memory B Cell OSP-specific responses.
Mean antigen-specific IgM memory B cell responses to Ogawa (A) and Inaba (B) OSP determined from ELISA measurements of lymphocyte culture supernatant. Statistically significant differences relative to baseline (Day 0) are indicated. (* = P<0.05, ** = P<0.01, *** = P<0.001, **** = P<0.0001).
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