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

Vaccine. 2018 May 11;36(20):2768-2773. doi: 10.1016/j.vaccine.2018.04.011. Epub 2018 Apr 11.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Antibodies, Bacterial / blood
  • B-Lymphocytes / immunology*
  • Cholera / prevention & control*
  • Cholera Toxin / immunology
  • Cholera Vaccines / administration & dosage
  • Cholera Vaccines / immunology*
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Immunologic Memory*
  • Lipopolysaccharides / immunology*
  • Time Factors
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Vibrio cholerae O1 / immunology*

Substances

  • Antibodies, Bacterial
  • Cholera Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Lipopolysaccharides
  • Vaccines, Attenuated
  • cholera vaccine CVD 103-HgR
  • Cholera Toxin

Associated data

  • ClinicalTrials.gov/NCT01895855