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- Title
A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A.
- Authors
Enotarpi, Jacopo; Tontini, Marta; Balocchi, Cristiana; van der Es, Daan; Auberger, Ludovic; Balducci, Evita; Carboni, Filippo; Proietti, Daniela; Casini, Daniele; Filippov, Dmitri V.; Overkleeft, Hermen S.; van der Marel, Gijsbert A.; Colombo, Cinzia; Romano, Maria Rosaria; Berti, Francesco; Costantino, Paolo; Codeé, Jeroen D. C.; Lay, Luigi; Adamo, Roberto
- Abstract
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. The Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) is a component of commercial vaccines, but is unstable. Here, the authors generate glycomimetic oligomers that demonstrate higher stability than their natural counterparts and induce protective antibodies in mice.
- Subjects
NEISSERIA meningitidis; IMMUNOGLOBULINS; VACCINE development; VIRAL antibodies; VACCINES; IN vivo studies
- Publication
Nature Communications, 2020, Vol 11, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-18279-x