VACCINATION AND THE EVOLUTIONARY DYNAMICS OF PNEUMOCOCCI

肺炎球菌等抗原性不同的病原体对疫苗设计提出了新的进化挑战。使用针对可变抗原的疫苗可导致，并已导致没有携带疫苗中包括的抗原变体的病原体类型的增加。肺炎链球菌(肺炎球菌)群体对疫苗诱导的选择性压力的这种进化反应，称为“血清型替换”，可能反过来导致疾病模式的转变。血清型替换可能是有益的，也可能是有害的，这取决于替换类型导致疾病的能力。这里提出的研究是为了确定在未接种疫苗的人群中肺炎球菌观察到的群体生物学背后的生物学机制，并利用这一知识来预测当疫苗广泛使用时人群将如何反应。肺炎球菌在小鼠体内携带的实验模型和流行病学数据的分析将被用来表征肺炎球菌多样性和种群生物学的生态机制，这些机制将被纳入肺炎球菌携带和传播的数学模型。该模型的预测将使用肺炎球菌结合疫苗社区随机试验中肺炎球菌分离株的分子流行病学研究。其具体目的是：1)在鼻腔携带的实验室小鼠模型中，定量描述肺炎球菌菌株之间的种群-生物相互作用。2)利用分子流行病学分型方法，通过研究肺炎球菌疫苗接种后肺炎链球菌种群的变化，研究自然肺炎球菌携带后抗体介导免疫的发展过程以及这种免疫对肺炎球菌动态的影响，并利用这些模型来确定现有传播模式的机制。

Antigenically diverse pathogens such as pneumococci present novel evolutionary challenges for vaccine design. The use of vaccines directed against variable antigens can cause, and has caused, increases in pathogen types not carrying the antigenic variants included in the vaccine. this evolutionary response of the population of streptococcus pneumonia (pneumococcus) to vaccine -induced selective pressure, known as "serotype replacement," may in turn cause a shift in patterns of disease. serotype replacement may be either beneficial or harmful, depending on the ability of the replacing types to cause disease. The research proposed here is to ascertain is designed to ascertain the biological mechanisms underlying the observed population biology of pneumococci in unvaccinated populations and to use this knowledge to predict how the population will respond when vaccines are widely used. Experimental models of pneumococcal carriage in mice and analysis of epidemiological data will be used to characterize the ecological mechanisms underlying pneumococcal diversity and population biology, and these mechanisms will be incorporated into a mathematical model of pneumococcal carriage and transmission. The predictions of this model will be using molecular epidemiological studies of pneumococcal isolates from community randomized trial of the pneumococcal conjugate vaccine. the specific aims are: 1) to characterize quantitatively the population- biological interactions between pneumococcal strains in a laboratory mouse model of intra nasal carriage. 2) to characterize the development of antibody-mediated immunity due to natural pneumococcal carriages and the impact of this immunity on dynamics of pneumococci, to use these models to identify the mechanisms underlying existing patterns of the transmission mathematical models by characterizing the changes in pneumococcal populations following vaccination, using molecular epidemiological typing methods.