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O antigen allows B. parapertussis to evade B. pertussis vaccine-induced immunity by blocking binding and functions of cross-reactive antibodies.

Zhang X, Rodríguez ME, Harvill ET - PLoS ONE (2009)

Bottom Line: The wP was much more protective against an isogenic B. parapertussis strain lacking O-antigen than its wild-type counterpart.Interestingly, B. parapertussis-specific antibodies provided in addition to either wP or aP were sufficient to very rapidly reduce B. parapertussis numbers in mouse lungs.This study identifies a mechanism by which one pathogen escapes immunity induced by vaccination against a closely related pathogen and may explain why B. parapertussis prevalence varies substantially between populations with different vaccination strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America.

ABSTRACT
Although the prevalence of Bordetella parapertussis varies dramatically among studies in different populations with different vaccination regimens, there is broad agreement that whooping cough vaccines, composed only of B. pertussis antigens, provide little if any protection against B. parapertussis. In C57BL/6 mice, a B. pertussis whole-cell vaccine (wP) provided modest protection against B. parapertussis, which was dependent on IFN-gamma. The wP was much more protective against an isogenic B. parapertussis strain lacking O-antigen than its wild-type counterpart. O-antigen inhibited binding of wP-induced antibodies to B. parapertussis, as well as antibody-mediated opsonophagocytosis in vitro and clearance in vivo. aP-induced antibodies also bound better in vitro to the O-antigen mutant than to wild-type B. parapertussis, but aP failed to confer protection against wild-type or O antigen-deficient B. parapertussis in mice. Interestingly, B. parapertussis-specific antibodies provided in addition to either wP or aP were sufficient to very rapidly reduce B. parapertussis numbers in mouse lungs. This study identifies a mechanism by which one pathogen escapes immunity induced by vaccination against a closely related pathogen and may explain why B. parapertussis prevalence varies substantially between populations with different vaccination strategies.

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O-antigen inhibits the binding of B. pertussis vaccine-induced antibodies to live, but not denatured, B. parapertussis cells.(A) Western blots were performed on lysates of indicated bacteria probed with serum antibodies collected from mice that were vaccinated with aP, adjuvant only (Adj) or wP. (B) Heat-inactivated or (C) live B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) were coated on ELISA plate. Serum antibody titer of mice vaccinated with aP or wP is expressed as mean of the end point titers of four independent samples ± the standard error. ** indicates P≤0.01. The dashed line indicates the limit of detection.
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pone-0006989-g005: O-antigen inhibits the binding of B. pertussis vaccine-induced antibodies to live, but not denatured, B. parapertussis cells.(A) Western blots were performed on lysates of indicated bacteria probed with serum antibodies collected from mice that were vaccinated with aP, adjuvant only (Adj) or wP. (B) Heat-inactivated or (C) live B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) were coated on ELISA plate. Serum antibody titer of mice vaccinated with aP or wP is expressed as mean of the end point titers of four independent samples ± the standard error. ** indicates P≤0.01. The dashed line indicates the limit of detection.

Mentions: We have previously shown that antibodies are required for anamnestic immunity to B. parapertussis [34]. To determine whether B. pertussis vaccines induce antibodies that recognize and/or protect against B. parapertussis, we first tested whether antibody responses are cross-reactive between strains and if O-antigen affects the responsiveness of antibodies. In a western blot, whole cell extracts of B. pertussis, wild-type and O-antigen deficient B. parapertussis were probed with serum antibodies from aP, adjuvant only, wP vaccinated or naïve mice. Compared to the control, aP vaccination induced serum antibodies that recognized distinct antigens present in all three bacteria, although the size and intensity of bands appeared to differ between B. pertussis and B. parapertussis. While wP-induced serum antibodies recognized four major bands in denatured B. parapertussis, they recognize more antigens in B. pertussis, especially those of high molecular weights (Figure 5A).


O antigen allows B. parapertussis to evade B. pertussis vaccine-induced immunity by blocking binding and functions of cross-reactive antibodies.

Zhang X, Rodríguez ME, Harvill ET - PLoS ONE (2009)

O-antigen inhibits the binding of B. pertussis vaccine-induced antibodies to live, but not denatured, B. parapertussis cells.(A) Western blots were performed on lysates of indicated bacteria probed with serum antibodies collected from mice that were vaccinated with aP, adjuvant only (Adj) or wP. (B) Heat-inactivated or (C) live B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) were coated on ELISA plate. Serum antibody titer of mice vaccinated with aP or wP is expressed as mean of the end point titers of four independent samples ± the standard error. ** indicates P≤0.01. The dashed line indicates the limit of detection.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2737124&req=5

pone-0006989-g005: O-antigen inhibits the binding of B. pertussis vaccine-induced antibodies to live, but not denatured, B. parapertussis cells.(A) Western blots were performed on lysates of indicated bacteria probed with serum antibodies collected from mice that were vaccinated with aP, adjuvant only (Adj) or wP. (B) Heat-inactivated or (C) live B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) were coated on ELISA plate. Serum antibody titer of mice vaccinated with aP or wP is expressed as mean of the end point titers of four independent samples ± the standard error. ** indicates P≤0.01. The dashed line indicates the limit of detection.
Mentions: We have previously shown that antibodies are required for anamnestic immunity to B. parapertussis [34]. To determine whether B. pertussis vaccines induce antibodies that recognize and/or protect against B. parapertussis, we first tested whether antibody responses are cross-reactive between strains and if O-antigen affects the responsiveness of antibodies. In a western blot, whole cell extracts of B. pertussis, wild-type and O-antigen deficient B. parapertussis were probed with serum antibodies from aP, adjuvant only, wP vaccinated or naïve mice. Compared to the control, aP vaccination induced serum antibodies that recognized distinct antigens present in all three bacteria, although the size and intensity of bands appeared to differ between B. pertussis and B. parapertussis. While wP-induced serum antibodies recognized four major bands in denatured B. parapertussis, they recognize more antigens in B. pertussis, especially those of high molecular weights (Figure 5A).

Bottom Line: The wP was much more protective against an isogenic B. parapertussis strain lacking O-antigen than its wild-type counterpart.Interestingly, B. parapertussis-specific antibodies provided in addition to either wP or aP were sufficient to very rapidly reduce B. parapertussis numbers in mouse lungs.This study identifies a mechanism by which one pathogen escapes immunity induced by vaccination against a closely related pathogen and may explain why B. parapertussis prevalence varies substantially between populations with different vaccination strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America.

ABSTRACT
Although the prevalence of Bordetella parapertussis varies dramatically among studies in different populations with different vaccination regimens, there is broad agreement that whooping cough vaccines, composed only of B. pertussis antigens, provide little if any protection against B. parapertussis. In C57BL/6 mice, a B. pertussis whole-cell vaccine (wP) provided modest protection against B. parapertussis, which was dependent on IFN-gamma. The wP was much more protective against an isogenic B. parapertussis strain lacking O-antigen than its wild-type counterpart. O-antigen inhibited binding of wP-induced antibodies to B. parapertussis, as well as antibody-mediated opsonophagocytosis in vitro and clearance in vivo. aP-induced antibodies also bound better in vitro to the O-antigen mutant than to wild-type B. parapertussis, but aP failed to confer protection against wild-type or O antigen-deficient B. parapertussis in mice. Interestingly, B. parapertussis-specific antibodies provided in addition to either wP or aP were sufficient to very rapidly reduce B. parapertussis numbers in mouse lungs. This study identifies a mechanism by which one pathogen escapes immunity induced by vaccination against a closely related pathogen and may explain why B. parapertussis prevalence varies substantially between populations with different vaccination strategies.

Show MeSH
Related in: MedlinePlus