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Rational design of adjuvants targeting the C-type lectin Mincle

This article was selected as "Article of the month" by the French Society for Biochemistry & Molecular Biology

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Vaccination is a highly effective method of preventing infectious diseases. However, adjuvants are needed to enhance the immunogenicity of vaccine antigens. For many years, the development of adjuvants has been an empirical process. Scientists from the team "Immunomodulation by Mycobacterial Lipids and Glycoconjugates" at the Institute of Pharmacology and Structural Biology show that new generation adjuvants can be designed on a rational basis. This study is published in the Proceedings of the National Academy of Sciences of the USA, on 21 Feb 2017.

 

Vaccines are mainly used to fight infectious diseases but they can also help to treat cancer. Historically, vaccines have been made with live attenuated or dead pathogens. For many pathogens, however, such vaccines have not been successfully developed. Moreover, they can be associated to side effects. Current efforts aim at the development of subunit vaccines that induce a well-defined immune response against specific antigens, from pathogens (virus, bacteria) as well as from tumors.

 

However, vaccine antigens are often poorly immunogenic and require additional components, termed adjuvants, to help stimulate protective immunity. Most of the adjuvants in use have been developed empirically without a clear understanding of their mechanisms of action. Adjuvants inducing a strong humoral immunity, which protects against extracellular pathogens, are available. But, adjuvants directing the development of robust cellular immune responses, required to fight against intracellular pathogens or tumors, are still needed. Recently, the C-type lectin receptor Mincle was found to elicit such responses on the recognition of microbial glycolipids, thereby providing a basis for the rational design of new adjuvants. In the present study, the scientists used a multidisciplinary approach, combining chemical synthesis, cell biology, and molecular modeling to decipher the molecular bases of ligand recognition by the receptor. This led them to synthesize new compounds inducing stronger immune responses, while being less toxic, than the currently available Mincle ligands, and that represent new powerful adjuvant molecules.

 

This work was performed in collaboration with the biotech company Invivogen (Toulouse), the “Laboratoire d’Ingénierie des Systèmes Biologiques et des Procédés” (Toulouse) and the "Centro Nacional de Investigaciones Cardiovasculares Carlos III (Madrid).

 

Reference:

Decout, A., Silva-Gomes, S., Drocourt, D., Barbe, S., André, I., Cueto, F.J., Lioux, T., Sancho, D., Pérouzel, E., Vercellone, A., Prandi, J., Gilleron, M., Tiraby, G. & Nigou, J. (2017) Rational design of adjuvants targeting the C-type lectin Mincle. PNAS, doi: 10.1073/pnas.1612421114.

Contact : 

Jérôme Nigou

 

To read the article ... and the Press Release (in french)