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

脂多糖特异性记忆 B 细胞对减毒活霍乱疫苗的反应与预防霍乱弧菌感染有关

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作者:Douglas J Haney, Michael D Lock, Marc Gurwith, Jakub K Simon, Glenn Ishioka, Mitchell B Cohen, Beth D Kirkpatrick, Caroline E Lyon, Wilbur H Chen, Marcelo B Sztein, Myron M Levine, Jason B Harris

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.

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.

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).

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