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T cells control the generation of nanomolar-affinity anti-glycan antibodies
Zinaida Polonskaya, … , M.G. Finn, Luc Teyton
Zinaida Polonskaya, … , M.G. Finn, Luc Teyton
Published March 13, 2017
Citation Information: J Clin Invest. 2017;127(4):1491-1504. https://doi.org/10.1172/JCI91192.
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Research Article Immunology Vaccines

T cells control the generation of nanomolar-affinity anti-glycan antibodies

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Abstract

Vaccines targeting glycan structures at the surface of pathogenic microbes must overcome the inherent T cell–independent nature of immune responses against glycans. Carbohydrate conjugate vaccines achieve this by coupling bacterial polysaccharides to a carrier protein that recruits heterologous CD4 T cells to help B cell maturation. Yet they most often produce low- to medium-affinity immune responses of limited duration in immunologically fit individuals and disappointing results in the elderly and immunocompromised patients. Here, we hypothesized that these limitations result from suboptimal T cell help. To produce the next generation of more efficacious conjugate vaccines, we have explored a synthetic design aimed at focusing both B cell and T cell recognition to a single short glycan displayed at the surface of a virus-like particle. We tested and established the proof of concept of this approach for 2 serotypes of Streptococcus pneumoniae. In both cases, these vaccines elicited serotype-specific, protective, and long-lasting IgG antibodies of nanomolar affinity against the target glycans in mice. We further identified a requirement for CD4 T cells in the anti-glycan antibody response. Our findings establish the design principles for improved glycan conjugate vaccines. We surmise that the same approach can be used for any microbial glycan of interest.

Authors

Zinaida Polonskaya, Shenglou Deng, Anita Sarkar, Lisa Kain, Marta Comellas-Aragones, Craig S. McKay, Katarzyna Kaczanowska, Marie Holt, Ryan McBride, Valle Palomo, Kevin M. Self, Seth Taylor, Adriana Irimia, Sanjay R. Mehta, Jennifer M. Dan, Matthew Brigger, Shane Crotty, Stephen P. Schoenberger, James C. Paulson, Ian A. Wilson, Paul B. Savage, M.G. Finn, Luc Teyton

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Figure 1

Response of humans and mice to licensed CVs.

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Response of humans and mice to licensed CVs.
(A and B) IgM (A) and IgG (...
(A and B) IgM (A) and IgG (B) response in the plasma of 6 pediatric and 6 adult subjects to 23 S. pneumoniae serotype polysaccharides immobilized on a glycan microarray (Supplemental Table 1 and ref. 38). Plasma dilution 1:400. Each graph represents an individual. (C) Response in the sera of mice, immunized with Prevnar-13 (n = 4 mice) or naive (n = 2 mice), to 23 S. pneumoniae serotype polysaccharides. Each graph represents an individual mouse. Data are presented as the mean ± SD based on 4 technical replicates.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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