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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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Passive transfer of B. parapertussis–specific antibodies rapidly reduces B. parapertussis colonization in aP and wP vaccinated animals.Groups of four C57BL/6 mice were (B) left untreated (−) or vaccinated with (A) aP, (B) wPP or wP. Mice lacking a transfer of antibodies (−) or given naïve serum (NS), wP-induced serum (wP IS) or wPP-induced serum (wPP IS) were challenged with B. parapertussis. Mice were sacrificed three days post-challenge and the number of CFUs recovered from the respiratory tract is expressed as the Log10 mean ± the standard error. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.
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pone-0006989-g010: Passive transfer of B. parapertussis–specific antibodies rapidly reduces B. parapertussis colonization in aP and wP vaccinated animals.Groups of four C57BL/6 mice were (B) left untreated (−) or vaccinated with (A) aP, (B) wPP or wP. Mice lacking a transfer of antibodies (−) or given naïve serum (NS), wP-induced serum (wP IS) or wPP-induced serum (wPP IS) were challenged with B. parapertussis. Mice were sacrificed three days post-challenge and the number of CFUs recovered from the respiratory tract is expressed as the Log10 mean ± the standard error. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.

Mentions: We have previously shown that both antibodies and T cells are required for anamnestic protective immunity against B. parapertussis [34]. Although wP vaccination induced T cell responses that were cross-reactive (Figure 4) and antibodies that bound antigens from heat-killed B. parapertussis (Figure 5B), O-antigen decreased the binding of these antibodies to live B. parapertussis (Figure 5), the opsonophagocytosis mediated by these antibodies in vitro (Figure 6, Figure 7, Figure 8) and their antibody-mediated clearance in vivo (Figure 9). Based on these observations, we hypothesized that wP induces sufficient T cell response but the antibody response is not sufficient to clear B. parapertussis because O-antigen protects B. parapertussis from wP-induced antibodies. If this were the case, then adding antibodies that bind live B. parapertussis should render wP induced immunity sufficient to rapidly clear B. parapertussis. To test this, mice were vaccinated with aP (Figure 10A) or wP (Figure 10B), these vaccinated mice were left untreated or given naïve, wP or wPP-induced serum antibodies at the time of B. parapertussis challenge and sacrificed three days after challenge. To compare the protective immunity to that generated by B. parapertussis, a group of mice were vaccinated with wPP and adoptively transferred with wPP-induced antibodies. Less than 100 CFUs of B. parapertussis were recovered in the LRT of this group of mice by day 3 post-challenge (Figure 10B). The very high titers of this wPP-induced serum antibodies alone had modest effect on reducing B. parapertussis numbers (Figure 10B), consistent with prior results with convalescent serum [30], [39]. In both aP and wP vaccinated mice, naïve sera had no effect, indicating that components in the serum other than those induced by vaccination do not affect bacteria numbers. Transfer of wP-induced sera had no effect on B. parapertussis colonization throughout the respiratory tract. However, B. parapertussis numbers were significantly lower in the LRT of both aP and wP vaccinated animals given wPP-induced sera than in those given naïve sera (Figure 10). These data suggest that the addition of B. parapertussis specific antibodies is sufficient to render wP and aP effective 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)

Passive transfer of B. parapertussis–specific antibodies rapidly reduces B. parapertussis colonization in aP and wP vaccinated animals.Groups of four C57BL/6 mice were (B) left untreated (−) or vaccinated with (A) aP, (B) wPP or wP. Mice lacking a transfer of antibodies (−) or given naïve serum (NS), wP-induced serum (wP IS) or wPP-induced serum (wPP IS) were challenged with B. parapertussis. Mice were sacrificed three days post-challenge and the number of CFUs recovered from the respiratory tract is expressed as the Log10 mean ± the standard error. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2737124&req=5

pone-0006989-g010: Passive transfer of B. parapertussis–specific antibodies rapidly reduces B. parapertussis colonization in aP and wP vaccinated animals.Groups of four C57BL/6 mice were (B) left untreated (−) or vaccinated with (A) aP, (B) wPP or wP. Mice lacking a transfer of antibodies (−) or given naïve serum (NS), wP-induced serum (wP IS) or wPP-induced serum (wPP IS) were challenged with B. parapertussis. Mice were sacrificed three days post-challenge and the number of CFUs recovered from the respiratory tract is expressed as the Log10 mean ± the standard error. ** indicates P≤0.01. The limit of detection is indicated as the lower limit of the y axes.
Mentions: We have previously shown that both antibodies and T cells are required for anamnestic protective immunity against B. parapertussis [34]. Although wP vaccination induced T cell responses that were cross-reactive (Figure 4) and antibodies that bound antigens from heat-killed B. parapertussis (Figure 5B), O-antigen decreased the binding of these antibodies to live B. parapertussis (Figure 5), the opsonophagocytosis mediated by these antibodies in vitro (Figure 6, Figure 7, Figure 8) and their antibody-mediated clearance in vivo (Figure 9). Based on these observations, we hypothesized that wP induces sufficient T cell response but the antibody response is not sufficient to clear B. parapertussis because O-antigen protects B. parapertussis from wP-induced antibodies. If this were the case, then adding antibodies that bind live B. parapertussis should render wP induced immunity sufficient to rapidly clear B. parapertussis. To test this, mice were vaccinated with aP (Figure 10A) or wP (Figure 10B), these vaccinated mice were left untreated or given naïve, wP or wPP-induced serum antibodies at the time of B. parapertussis challenge and sacrificed three days after challenge. To compare the protective immunity to that generated by B. parapertussis, a group of mice were vaccinated with wPP and adoptively transferred with wPP-induced antibodies. Less than 100 CFUs of B. parapertussis were recovered in the LRT of this group of mice by day 3 post-challenge (Figure 10B). The very high titers of this wPP-induced serum antibodies alone had modest effect on reducing B. parapertussis numbers (Figure 10B), consistent with prior results with convalescent serum [30], [39]. In both aP and wP vaccinated mice, naïve sera had no effect, indicating that components in the serum other than those induced by vaccination do not affect bacteria numbers. Transfer of wP-induced sera had no effect on B. parapertussis colonization throughout the respiratory tract. However, B. parapertussis numbers were significantly lower in the LRT of both aP and wP vaccinated animals given wPP-induced sera than in those given naïve sera (Figure 10). These data suggest that the addition of B. parapertussis specific antibodies is sufficient to render wP and aP effective 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