Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection

Abstract

Background: The single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naïve adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1-2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response.

Methods: In a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera.

Results: There was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = -0.56, p < 0.001).

Discussion: Oral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection.

Clinical trials registration: NCT01895855.

Keywords: CVD 103-HgR; Cholera; Cholera-naïve; Duration of protection; Live vaccine; Memory B cells.

Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1. Effect of Placebo on Antigen-Specific Memory B Cell Percentages at 90 Days, Effect of Vaccination at 90 and 180 Days, and Effect of V. cholerae Challenge at 180 Days

Note that for the LPS-specific IgG results on Day 180, the nonparametric 95% confidence interval on the median overlaps one even though the signed-rank test of statistical significance produced a p-value less than 0.05 because the signed-rank test assesses both the direction and magnitude of changes over time and provides greater statistical power.

Figure 2. Association between Vaccine-Induced LPS-Specific IgA Memory B Cell Response and Outcome

The center line of each box represent the median, and the upper and lower edges of the box represent the 75th and 25th percentiles.