Douglas J Haney1, Michael D Lock2, Marc Gurwith2, Jakub K Simon2, Glenn Ishioka2, Mitchell B Cohen3, Beth D Kirkpatrick4, Caroline E Lyon4, Wilbur H Chen5, Marcelo B Sztein5, Myron M Levine5, Jason B Harris6. 1. PaxVax, Inc., Redwood City, CA, United States. Electronic address: haney_doug@hotmail.com. 2. PaxVax, Inc., Redwood City, CA, United States. 3. University of Alabama at Birmingham, Birmingham, AL, United States. 4. Vaccine Testing Center, University of Vermont, College of Medicine, Burlington, VT, United States. 5. Center for Vaccine Development (CVD), University of Maryland School of Medicine, Baltimore, MD, United States. 6. Division of Global Health, Massachusetts General Hospital for Children, Boston, MA, United States; Department of Pediatrics, Harvard Medical School, Cambridge, MA, United States. Electronic address: jbharris@mgh.harvard.edu.
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.
RCT Entities:
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.
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