|Title||T cells control the generation of nanomolar-affinity anti-glycan antibodies.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Polonskaya Z, Deng S, Sarkar A, Kain L, Comellas-Aragones M, McKay CS, Kaczanowska K, Holt M, McBride R, Palomo V, Self KM, Taylor S, Irimia A, Mehta SR, Dan JM, Brigger M, Crotty S, Schoenberger SP, Paulson JC, Wilson IA, Savage PB, Finn MG, Teyton L|
|Journal||J Clin Invest|
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.
|Alternate Journal||J. Clin. Invest.|
|Grant List||UM1 AI100663 / AI / NIAID NIH HHS / United States|
T cells control the generation of nanomolar-affinity anti-glycan antibodies.