5JOP

Crystal structure of anti-glycan antibody Fab14.22 in complex with Streptococcus pneumoniae serotype 14 tetrasaccharide at 1.75 A

Summary for 5JOP

• Entry DOI: 10.2210/pdb5jop/pdb
• Related: 5JOR
• Descriptor: Fab 14.22 light chain, Fab14.22 heavy chain, beta-D-galactopyranose-(1-4)-beta-D-glucopyranose-(1-6)-[beta-D-galactopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: s. pneumoniae serotype 14, anti-glycan b cells, synthetic conjugate vaccine, nanomolar affinity anti-glycan antibody, immune system, immune system-bacterial glycan complex
• Biological source: Mus musculus; More
• Total number of polymer chains: 4
• Total formula weight: 105887.20

Authors

Sarkar, A.,Irimia, A.,Teyton, L.,Wilson, I.A. (deposition date: 2016-05-02, release date: 2017-03-22, Last modification date: 2023-09-27)

Primary citation

Polonskaya, Z.,Deng, S.,Sarkar, A.,Kain, L.,Comellas-Aragones, M.,McKay, C.S.,Kaczanowska, K.,Holt, M.,McBride, R.,Palomo, V.,Self, K.M.,Taylor, S.,Irimia, A.,Mehta, S.R.,Dan, J.M.,Brigger, M.,Crotty, S.,Schoenberger, S.P.,Paulson, J.C.,Wilson, I.A.,Savage, P.B.,Finn, M.G.,Teyton, L.
T cells control the generation of nanomolar-affinity anti-glycan antibodies.
J. Clin. Invest., 127:1491-1504, 2017

PubMed 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.

PubMed: 28287405
DOI: 10.1172/JCI91192

Experimental method

X-RAY DIFFRACTION (1.75 Å)