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

J Clin Invest. 2017 Apr 3;127(4):1491-1504. doi: 10.1172/JCI91192. Epub 2017 Mar 13.


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.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial / blood*
  • Antibodies, Bacterial / chemistry
  • Antibody Affinity*
  • B-Lymphocytes / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Crystallography, X-Ray
  • Female
  • Glycopeptides / immunology
  • Humans
  • Hybridomas
  • Immunoglobulin G / blood
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Models, Molecular
  • Pneumococcal Infections / immunology*
  • Pneumococcal Infections / prevention & control
  • Pneumococcal Vaccines / chemistry
  • Pneumococcal Vaccines / immunology
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / immunology*
  • Protein Binding
  • Streptococcus pneumoniae / immunology
  • Vaccination
  • Vaccine Potency


  • Antibodies, Bacterial
  • Bacterial Proteins
  • Glycopeptides
  • Immunoglobulin G
  • Pneumococcal Vaccines
  • Polysaccharides, Bacterial