Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• The Journal of clinical investigation, 2017-04, Vol.127 (4), p.1491-1504

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.