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Vaccines 2019, 7(1), 18; https://doi.org/10.3390/vaccines7010018

Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans

1,2
and
1,2,*
1
Mucosal and Vaccine Research Program Colorado (MAVRC), Infectious Diseases, University of Colorado Denver, Aurora, CO 80045, USA
2
Eastern Colorado Rocky Mountain Veterans Affairs Medical Center, Denver, CO 80045, USA
*
Author to whom correspondence should be addressed.
Received: 31 December 2018 / Revised: 31 January 2019 / Accepted: 4 February 2019 / Published: 11 February 2019
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
Full-Text   |   PDF [293 KB, uploaded 27 February 2019]

Abstract

Bacterial pathogens expressing capsular polysaccharides are common causes of mucosal infections (pneumonia, intestinal), as well as often fatal, invasive infections (meningitis, bloodstream infections) in children and adults worldwide. These chemically simple but structurally complex carbohydrate structures on the bacterial surface confer resistance to recognition and clearance by the immune system through a range of mechanisms. Such recognition of capsular polysaccharides may be reduced by their limited ability to directly stimulate B cells and the T cells that may facilitate these humoral responses. The capsules may promote the evasion of complement deposition and activation and may sterically shield the recognition of other subjacent protein antigens by innate factors. Antibodies to capsular polysaccharides, elicited by infection and vaccines, may overcome these obstacles and facilitate bacterial agglutination at mucosal surfaces, as well as the opsonization and clearance of these organisms in tissues and the systemic compartment. However, the immunogenicity of these antigens may be limited by their lack of direct recognition by T cells (“T-independent” antigens) and their restricted ability to generate effective memory responses. In this review, we consider the mechanisms by which polysaccharides may initiate B cell responses and specific antibody responses and the role of T cells, particularly CD4+ follicular helper (TFH) cells to support this process. In addition, we also consider more recent counterintuitive data that capsular polysaccharides themselves may bind major histocompatibility antigen HLA class II to provide a more physiologic mechanism of T cell enhancement of B cell responses to capsular polysaccharides. Defining the contributions of T cells in the generation of effective humoral responses to the capsular polysaccharides will have important implications for understanding and translating this immunobiology for the development of more effective vaccines, to prevent the morbidity and mortality associated with these common mucosal and invasive pathogens in populations at risk. View Full-Text
Keywords: T-independent antigens; immunological responses; pneumococcal capsular polysaccharide; polysaccharide conjugate vaccine; antibody response; memory B cells; CD4+ T cells; carbohydrate-specific T cells T-independent antigens; immunological responses; pneumococcal capsular polysaccharide; polysaccharide conjugate vaccine; antibody response; memory B cells; CD4+ T cells; carbohydrate-specific T cells
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Jha, V.; Janoff, E.N. Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans. Vaccines 2019, 7, 18.

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