Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity

被引:89
作者
Zhang, Fan [1 ]
Lu, Ying-Jie [1 ]
Malley, Richard [1 ]
机构
[1] Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
INFLUENZAE TYPE-B; VACCINES; PROTEIN; RESPONSES; ANTIBODY; IL-17; MICE; COLONIZATION; TUBERCULOSIS; DIVERSITY;
D O I
10.1073/pnas.1307228110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Vaccines are among the most effective approaches to prevent and control many infectious diseases. Because of safety and reproducibility concerns, whole-cell vaccines (WCVs), made from live or killed microorganisms and including hundreds of antigenic components, have been mostly replaced by acellular or subunit vaccines composed of well-defined, purified antigen components. The efficacy of acellular vaccines is inferior to that of WCVs, however, for two major reasons: limited antigen diversity and reduced immunogenicity, especially in a lack of activation of antigen-specific T-cell immunity, which plays an important role in protection against mucosal and intracellular pathogens. Here we present the multiple antigen-presenting system (MAPS), which enables the creation of a macromolecular complex that mimics the properties of WCVs by integrating various antigen components, including polysaccharides and proteins, in the same construct and that induces multipronged immune responses, including antibody, Th1, and Th17 responses. Using antigens from various pathogens (Streptococcus pneumoniae, Salmonella typhi, and Mycobacterium tuberculosis), we demonstrate the versatility of the MAPS system and its feasibility for the design of unique defined-structure subunit vaccines to confer comprehensive protection via multiple immune mechanisms. Moreover, MAPS can serve as a tool for structure-activity analysis of cellular immunogens.
引用
收藏
页码:13564 / 13569
页数:6
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