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

Author:
Zhang, Fan, Lu, Ying-Jie, Malley, Richard
Source:
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.33 pp. 13564-13569
ISSN:
0027-8424
Subject:
Mycobacterium tuberculosis, Salmonella Typhi, Streptococcus, T-lymphocytes, antibodies, antigenic variation, antigens, immune response, infectious diseases, microorganisms, pathogens, pneumonia, polysaccharides, proteins, subunit vaccines
Abstract:
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 pneumonia e, 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.
Agid:
1737764