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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 blocks B. pertussis vaccine-induced antibodies from mediating adherence of B. parapertussis to PMNs.Naïve serum (white) or (A) aP, (B) wP, (C) wPP-induced serum (grey)-opsonized GFP-expressing bacteria were incubated with freshly isolated human peripheral blood PMNs. Representative histograms of flow cytometry analysis of these cells are shown. (D) Mean green fluorescence associated with PMNs incubated with GFP-expressing B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) opsonized with four independent indicated serum ± the standard error is shown. AU indicates arbitrary units. ** indicates P≤0.01.
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pone-0006989-g007: O-antigen blocks B. pertussis vaccine-induced antibodies from mediating adherence of B. parapertussis to PMNs.Naïve serum (white) or (A) aP, (B) wP, (C) wPP-induced serum (grey)-opsonized GFP-expressing bacteria were incubated with freshly isolated human peripheral blood PMNs. Representative histograms of flow cytometry analysis of these cells are shown. (D) Mean green fluorescence associated with PMNs incubated with GFP-expressing B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) opsonized with four independent indicated serum ± the standard error is shown. AU indicates arbitrary units. ** indicates P≤0.01.

Mentions: To examine if O-antigen blocking of opsonization results in inhibitory effects on attachment of B. parapertussis to phagocytes, bacteria opsonized with vaccine-induced antibodies were further incubated with polymorphonuclear leukocytes (PMN) for 20 mins and cell surface bound bacteria numbers were identified by flow cytometry. aP or wP-induced-antibody-opsonized B. pertussis attached to PMNs efficiently (Figure 7A, 7B, and 7D). B. parapertussis attached to PMN after opsonization with wPP-induced serum antibodies (Figure 7C and 7D), but neither aP nor wP-induced antibodies mediated attachment of this bacterium to PMNs (Figure 7A, 7B, and 7D). B. parapertussis lacking O-antigen, opsonized with aP or wP-induced antibodies, efficiently attached to phagocytes (Figure 7A, 7B, and 7D), indicating that O-antigen also inhibits this process.


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 blocks B. pertussis vaccine-induced antibodies from mediating adherence of B. parapertussis to PMNs.Naïve serum (white) or (A) aP, (B) wP, (C) wPP-induced serum (grey)-opsonized GFP-expressing bacteria were incubated with freshly isolated human peripheral blood PMNs. Representative histograms of flow cytometry analysis of these cells are shown. (D) Mean green fluorescence associated with PMNs incubated with GFP-expressing B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) opsonized with four independent indicated serum ± the standard error is shown. AU indicates arbitrary units. ** indicates P≤0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006989-g007: O-antigen blocks B. pertussis vaccine-induced antibodies from mediating adherence of B. parapertussis to PMNs.Naïve serum (white) or (A) aP, (B) wP, (C) wPP-induced serum (grey)-opsonized GFP-expressing bacteria were incubated with freshly isolated human peripheral blood PMNs. Representative histograms of flow cytometry analysis of these cells are shown. (D) Mean green fluorescence associated with PMNs incubated with GFP-expressing B. pertussis (black), B. parapertussis (white) or O-antigen deficient B. parapertussis (hatched) opsonized with four independent indicated serum ± the standard error is shown. AU indicates arbitrary units. ** indicates P≤0.01.
Mentions: To examine if O-antigen blocking of opsonization results in inhibitory effects on attachment of B. parapertussis to phagocytes, bacteria opsonized with vaccine-induced antibodies were further incubated with polymorphonuclear leukocytes (PMN) for 20 mins and cell surface bound bacteria numbers were identified by flow cytometry. aP or wP-induced-antibody-opsonized B. pertussis attached to PMNs efficiently (Figure 7A, 7B, and 7D). B. parapertussis attached to PMN after opsonization with wPP-induced serum antibodies (Figure 7C and 7D), but neither aP nor wP-induced antibodies mediated attachment of this bacterium to PMNs (Figure 7A, 7B, and 7D). B. parapertussis lacking O-antigen, opsonized with aP or wP-induced antibodies, efficiently attached to phagocytes (Figure 7A, 7B, and 7D), indicating that O-antigen also inhibits this process.

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