Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Proc Biol Sci. 2010 Jul 7;277(1690):2017-25. doi: 10.1098/rspb.2010.0010. Epub 2010 Mar 3.
Despite over 50 years of population-wide vaccination, whooping cough incidence is on the rise. Although Bordetella pertussis is considered the main causative agent of whooping cough in humans, Bordetella parapertussis infections are not uncommon. The widely used acellular whooping cough vaccines (aP) are comprised solely of B. pertussis antigens that hold little or no efficacy against B. parapertussis. Here, we ask how aP vaccination affects competitive interactions between Bordetella species within co-infected rodent hosts and thus the aP-driven strength and direction of in-host selection. We show that aP vaccination helped clear B. pertussis but resulted in an approximately 40-fold increase in B. parapertussis lung colony-forming units (CFUs). Such vaccine-mediated facilitation of B. parapertussis did not arise as a result of competitive release; B. parapertussis CFUs were higher in aP-relative to sham-vaccinated hosts regardless of whether infections were single or mixed. Further, we show that aP vaccination impedes host immunity against B. parapertussis-measured as reduced lung inflammatory and neutrophil responses. Thus, we conclude that aP vaccination interferes with the optimal clearance of B. parapertussis and enhances the performance of this pathogen. Our data raise the possibility that widespread aP vaccination can create hosts more susceptible to B. parapertussis infection.
尽管已经进行了超过 50 年的全民疫苗接种,但百日咳的发病率仍在上升。虽然博德特氏菌(Bordetella pertussis)被认为是人类百日咳的主要病原体,但副百日咳博德特氏菌(Bordetella parapertussis)的感染并不少见。广泛使用的无细胞百日咳疫苗(aP)仅由 B. pertussis 抗原组成,对 B. parapertussis 的疗效甚微或没有疗效。在这里,我们探讨了 aP 疫苗接种如何影响共同感染的啮齿动物宿主中博德特氏菌种之间的竞争相互作用,以及 aP 驱动的宿主内选择的强度和方向。我们发现,aP 疫苗接种有助于清除 B. pertussis,但导致 B. parapertussis 肺部集落形成单位(CFU)增加约 40 倍。这种疫苗介导的副百日咳博德特氏菌的促进作用并非由于竞争释放所致;与假疫苗接种宿主相比,aP 宿主中的 B. parapertussis CFU 更高,无论感染是单一还是混合的。此外,我们还表明,aP 疫苗接种会阻碍宿主对 B. parapertussis 的免疫反应——表现为肺部炎症和中性粒细胞反应减少。因此,我们得出结论,aP 疫苗接种会干扰 B. parapertussis 的最佳清除,并增强该病原体的性能。我们的数据提出了一种可能性,即广泛使用 aP 疫苗接种可能会使宿主更容易感染副百日咳博德特氏菌。