Effects of aging and HIV infection on the response to pneumococcal vaccine

衰老和艾滋病毒感染对肺炎球菌疫苗反应的影响

基本信息

批准号：
9141744
负责人：
Liise-anne Pirofski
金额：
$ 26.66万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9141744
关键词：
AIDS/HIV problem Adult Affect Aging Anti-Retroviral Agents Antibodies Antibody Repertoire Antibody Response B-Lymphocyte Subsets B-Lymphocytes Biological Assay Biological Markers Carrier Proteins Child Communities Conjugate Vaccines Data Development Elderly Future Gene Expression Genes Goals HIV HIV Infections Hospitals Immunocompetent Immunocompromised Host Individual Infant Knowledge Link MMP11 gene Measures Mediating Medical Molecular Molecular Profiling Morbidity - disease rate Mus Pathway interactions Patients Pneumococcal Infections Pneumococcal vaccine Pneumonia Polysaccharides Population Prevention Proteins Public Health Research Risk Risk Factors Sepsis Serological Serotyping Serum Streptococcus pneumoniae Systems Biology Target Populations Time Vaccination Vaccines Validation Work age effect clinically relevant cohort cost disorder risk driving force falls immunogenic immunogenicity immunosenescence improved in vitro activity middle age mortality multidisciplinary novel novel strategies peripheral blood prevent public health relevance response routine care stem vaccine efficacy vaccine response

项目摘要

DESCRIPTION: HIV-infected (HIV+) and elderly individuals are the main adult populations for whom pneumococcal vaccine is recommended as they are highly susceptible to Streptococcus pneumoniae (pneumococcus), the leading cause of community acquired and in-hospital pneumonia in the U.S. and globally. In late fall 2012, a 13 valent pneumococcal capsular polysaccharide (PPS) conjugate vaccine (PCV13) recommended for infants/children since 2010 and approved for adults since 2011, was recommended for HIV+ adults. The goal of this project, submitted in response to PAR 12-175 "Multidisciplinary studies of HIV/AIDS and Aging", is to determine the effects of aging and HIV infection PCV13 response. In prior work, our group discovered links between B cell and antibody repertoire deficiencies and impaired PPS antibody responses in HIV+ individuals and identified novel functional activities of PPS antibodies that protect against pneumococcal sepsis and pneumonia in mice. Informed by these studies, we will perform in depth analyses of the serological, B cell, functional and molecular responses to PCV13 of middle aged (50-65 yrs) and elderly (>65 yrs) HIV+ and HIV- individuals and assemble the data into serological and molecular signatures of PCV13 response. We will use standard serological and functional assays along with novel assays of PPS antibody functional activity against clinically important pneumococcal serotypes that PCV13 was developed to prevent. Then, we will use systems biology to identify molecular mechanisms of PCV13 response and assemble B cell, serological and transcriptional profiles into biomarkers of response. The specific aims of this project are: 1) To determine the effects of age and HIV infection on the antibody and B cell response to PCV13; 2) To determine the effects of age and HIV infection on PCV13-elicited antibody functional activity; 3) To determine the effects of age and HIV infection on the molecular response to PCV13. As biomarkers of adult pneumococcal vaccine response are not available, those identified in this study will fill a major gap and provid a platform to decipher PCV13 efficacy, a roadmap to guide future vaccine use in elderly HIV+ and HIV- individuals, clues to improve vaccine immunogenicity, and pathways to develop new approaches to prevent pneumococcal disease in those who are most at risk.

描述：建议感染HIV的（HIV+）和老年人是肺炎球菌疫苗的主要成年人，因为它们非常容易受到肺炎链球菌（肺炎链球菌）的影响，这是美国和全球范围内获得和院内肺炎的主要原因。 2012年秋末，自2010年以来，建议为婴儿/儿童提供13个Valent肺炎球菌囊囊多糖（PPS）共轭疫苗（PCV13），并自2011年以来被批准为HIV+成人。该项目的目标是响应于第12-175款“艾滋病毒/艾滋病和衰老的多学科研究”，是为了确定衰老和艾滋病毒感染PCV13反应的影响。在先前的工作中，我们的小组发现了B细胞与HIV+个体中的B细胞与抗体库缺乏症和PPS抗体反应受损，并确定了PPS抗体的新功能活性，这些抗体可预防小鼠中肺炎球菌败血症和肺炎。通过这些研究的了解，我们将对中年（50 - 65年）和老年人（> 65岁）HIV+和HIV个体的血清学，B细胞，功能和分子反应进行深入分析，并将数据汇总到PCV13响应的血清学和分子特征中。我们将使用标准的血清学和功能测定以及针对PCV13开发的临床重要肺炎球菌血清型的新型PPS抗体功能活性。然后，我们将使用系统生物学来鉴定PCV13响应的分子机制，并将B细胞，血清学和转录谱分解为反应的生物标志物。该项目的具体目的是：1）确定年龄和HIV感染对抗体和B细胞对PCV13的影响的影响； 2）确定年龄和HIV感染对PCV13引起的抗体功能活性的影响； 3）确定年龄和HIV感染对PCV13分子反应的影响。 As biomarkers of adult pneumococcal vaccine response are not available, those identified in this study will fill a major gap and provid a platform to decipher PCV13 efficacy, a roadmap to guide future vaccine use in elderly HIV+ and HIV- individuals, clues to improve vaccine immunogenicity, and pathways to develop new approaches to prevent pneumococcal disease in those who are most at risk.