RESUMEN

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20120-4.

RESUMEN

Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) consists of (1 → 6)-2-acetamido-2-deoxy-α-D-mannopyranosyl phosphate repeating units, O-acetylated at position C3 or C4. Glycomimetics appear attractive to overcome the CPS intrinsic lability in physiological media, due to cleavage of the phosphodiester bridge, and to develop a stable vaccine with longer shelf life in liquid formulation. Here, we generate a series of non-acetylated carbaMenA oligomers which are proven more stable than the CPS. An octamer (DP8) inhibits the binding of a MenA specific bactericidal mAb and polyclonal serum to the CPS, and is selected for further in vivo testing. However, its CRM197 conjugate raises murine antibodies towards the non-acetylated CPS backbone, but not the natural acetylated form. Accordingly, random O-acetylation of the DP8 is performed, resulting in a structure (Ac-carbaMenA) showing improved inhibition of anti-MenA CPS antibody binding and, after conjugation to CRM197, eliciting anti-MenA protective murine antibodies, comparably to the vaccine benchmark.

Asunto(s)

Glicoconjugados/síntesis química , Neisseria meningitidis Serogrupo A/inmunología , Polisacáridos Bacterianos/síntesis química , Vacunas Conjugadas , Animales , Anticuerpos Antibacterianos/análisis , Anticuerpos Neutralizantes/química , Cápsulas Bacterianas/inmunología , Biomimética/métodos , Glicoconjugados/inmunología , Ratones , Neisseria meningitidis Serogrupo A/química , Neisseria meningitidis Serogrupo A/efectos de los fármacos , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/inmunología , Vacunas Conjugadas/química , Vacunas Conjugadas/microbiología