Limits...
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.

Show MeSH

Related in: MedlinePlus

IFN-γ contributes to the protection against B. parapertussis by wP.Groups of four naïve (black and horizontally hatched) or wP vaccinated (white and vertically hatched) C57BL/6 mice were untreated (−) (black and white) or i.p. injected with (+) (horizontally and vertically hatched) anti-IFN-γ antibody, challenged with B. parapertussis and sacrificed 3 days post-challenge. The number of CFUs throughout the respiratory tract is expressed as the Log10 mean ± the standard error. * indicates P≤0.05. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2737124&req=5

pone-0006989-g004: IFN-γ contributes to the protection against B. parapertussis by wP.Groups of four naïve (black and horizontally hatched) or wP vaccinated (white and vertically hatched) C57BL/6 mice were untreated (−) (black and white) or i.p. injected with (+) (horizontally and vertically hatched) anti-IFN-γ antibody, challenged with B. parapertussis and sacrificed 3 days post-challenge. The number of CFUs throughout the respiratory tract is expressed as the Log10 mean ± the standard error. * indicates P≤0.05. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.

Mentions: In the vaccination studies above (Figure 1, Figure 2), protection against B. parapertussis correlates with the high IFN-γ responses of wP but not aP vaccinated animals (Figure 3). IFN-γ has been shown to contribute to leukocyte recruitment and the reduction of bacterial numbers during B. parapertussis infection (D.N. Wolfe, A.T. Karanikas, S.E. Hester, M.J. Kennett, E.T. Harvill, submitted for publication). To determine how the cross-reactive IFN-γ response after wP vaccination might contribute to its protection against B. parapertussis, naïve or wP vaccinated mice were left untreated or depleted of IFN-γ, challenged with B. pertussis or B. parapertussis and sacrificed 3 days later for bacterial enumeration. Vaccination or IFN-γ depletion had no effects on colonization of the nasal cavity (Figure 4). However, B. pertussis numbers were reduced by >99.9% and >99.5% in the lung and trachea of vaccinated mice compared to naïve mice regardless of the presence or absence of IFN-γ (Figure 4). Although wP reduced B. parapertussis numbers in the lung and trachea by about 98.6% and 99.6%, this effect was abolished in mice given IFN-γ neutralizing antibodies (Figure 4), indicating that IFN-γ contributes to the protection conferred by wP against B. parapertussis.


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)

IFN-γ contributes to the protection against B. parapertussis by wP.Groups of four naïve (black and horizontally hatched) or wP vaccinated (white and vertically hatched) C57BL/6 mice were untreated (−) (black and white) or i.p. injected with (+) (horizontally and vertically hatched) anti-IFN-γ antibody, challenged with B. parapertussis and sacrificed 3 days post-challenge. The number of CFUs throughout the respiratory tract is expressed as the Log10 mean ± the standard error. * indicates P≤0.05. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006989-g004: IFN-γ contributes to the protection against B. parapertussis by wP.Groups of four naïve (black and horizontally hatched) or wP vaccinated (white and vertically hatched) C57BL/6 mice were untreated (−) (black and white) or i.p. injected with (+) (horizontally and vertically hatched) anti-IFN-γ antibody, challenged with B. parapertussis and sacrificed 3 days post-challenge. The number of CFUs throughout the respiratory tract is expressed as the Log10 mean ± the standard error. * indicates P≤0.05. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.
Mentions: In the vaccination studies above (Figure 1, Figure 2), protection against B. parapertussis correlates with the high IFN-γ responses of wP but not aP vaccinated animals (Figure 3). IFN-γ has been shown to contribute to leukocyte recruitment and the reduction of bacterial numbers during B. parapertussis infection (D.N. Wolfe, A.T. Karanikas, S.E. Hester, M.J. Kennett, E.T. Harvill, submitted for publication). To determine how the cross-reactive IFN-γ response after wP vaccination might contribute to its protection against B. parapertussis, naïve or wP vaccinated mice were left untreated or depleted of IFN-γ, challenged with B. pertussis or B. parapertussis and sacrificed 3 days later for bacterial enumeration. Vaccination or IFN-γ depletion had no effects on colonization of the nasal cavity (Figure 4). However, B. pertussis numbers were reduced by >99.9% and >99.5% in the lung and trachea of vaccinated mice compared to naïve mice regardless of the presence or absence of IFN-γ (Figure 4). Although wP reduced B. parapertussis numbers in the lung and trachea by about 98.6% and 99.6%, this effect was abolished in mice given IFN-γ neutralizing antibodies (Figure 4), indicating that IFN-γ contributes to the protection conferred by wP against B. parapertussis.

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