Zangari Tonia, Wang Yang, Weiser Jeffrey N
Department of Microbiology, New York University School of Medicine, New York, New York, USA.
School of Medicine, Tsinghua University, Beijing, China.
mBio. 2017 Mar 14;8(2):e00188-17. doi: 10.1128/mBio.00188-17.
Epidemiological studies on show that rates of carriage are highest in early childhood and that the major benefit of the pneumococcal conjugate vaccine (PCV) is a reduction in the incidence of nasopharyngeal colonization through decreased transmission within a population. In this study, we sought to understand how anti- immunity affects nasal shedding of bacteria, the limiting step in experimental pneumococcal transmission. Using an infant mouse model, we examined the role of immunity (passed from mother to pup) on shedding and within-litter transmission of by pups infected at 4 days of life. Pups from both previously colonized immune and PCV-vaccinated mothers had higher levels of anti- IgG than pups from non-immune or non-vaccinated mothers and shed significantly fewer over the first 5 days of infection. By setting up cross-foster experiments, we demonstrated that maternal passage of antibody to pups either or post-natally decreases shedding. Passive immunization experiments showed that type-specific antibody to capsular polysaccharide is sufficient to decrease shedding and that the agglutinating function of immunoglobulin is required for this effect. Finally, we established that anti-pneumococcal immunity and anti-PCV vaccination block host-to-host transmission of Moreover, immunity in either the donor or recipient pups alone was sufficient to reduce rates of transmission, indicating that decreased shedding and protection from acquisition of colonization are both contributing factors. Our findings provide a mechanistic explanation for the reduced levels of transmission between hosts immune from prior exposure and among vaccinated children. Rates of carriage of the bacterial pathogen are highest among young children, and this is the target group for the pneumococcal conjugate vaccine (PCV). Epidemiological studies have suggested that a major benefit of the PCV is a reduction in host-to-host transmission, which also protects the non-vaccinated population ("herd immunity"). In this study, we examined the role of anti-pneumococcal immunity on nasal shedding and transmission of the pathogen using an infant mouse model. We found that shedding is decreased and transmission is blocked by anti-pneumococcal immunity and PCV vaccination. Additionally, transmission rates decreased if either the infected or contact pups were immune, indicating that reduced shedding and protection from the establishment of colonization are both contributing factors. Our study provides a mechanistic explanation for the herd immunity effect seen after the introduction of PCV and identifies potential points of intervention, which may have implications for future vaccine development.
关于[肺炎链球菌]的流行病学研究表明，携带率在幼儿期最高，而肺炎球菌结合疫苗（PCV）的主要益处是通过减少人群内传播来降低鼻咽部定植的发生率。在本研究中，我们试图了解抗[肺炎链球菌]免疫力如何影响细菌的鼻腔排出，这是实验性肺炎球菌传播中的限制步骤。使用幼鼠模型，我们研究了（从母体传递给幼崽的）免疫力对4日龄感染幼崽肺炎链球菌排出及窝内传播的作用。来自先前定植免疫和接种PCV疫苗的母体的幼崽，其抗[肺炎链球菌]IgG水平高于来自非免疫或未接种疫苗母体的幼崽，并且在感染的前5天排出的肺炎链球菌显著减少。通过设置交叉寄养实验，我们证明母体在产前或产后将抗体传递给幼崽可减少肺炎链球菌排出。被动免疫实验表明，针对荚膜多糖的型特异性抗体足以减少排出，且免疫球蛋白的凝集功能对此效应是必需的。最后，我们确定抗肺炎链球菌免疫力和PCV疫苗接种可阻断肺炎链球菌在宿主间的传播。此外，仅供体或受体幼崽具有免疫力就足以降低传播率，这表明排出减少和免受定植影响都是促成因素。我们的研究结果为既往暴露免疫的宿主之间以及接种疫苗儿童之间肺炎链球菌传播水平降低提供了机制解释。细菌病原体肺炎链球菌的携带率在幼儿中最高，这也是肺炎球菌结合疫苗（PCV）的目标人群。流行病学研究表明，PCV的主要益处是减少宿主间传播，这也保护了未接种疫苗的人群（“群体免疫”）。在本研究中，我们使用幼鼠模型研究了抗肺炎链球菌免疫力对病原体鼻腔排出和传播的作用。我们发现抗肺炎链球菌免疫力和PCV疫苗接种可减少排出并阻断传播。此外，如果感染或接触的幼崽具有免疫力，传播率会降低，这表明排出减少和免受定植影响都是促成因素。我们的研究为引入PCV后观察到的群体免疫效应提供了机制解释，并确定了潜在的干预点，这可能对未来疫苗开发有影响。
