O-acetylation of typhoid capsular polysaccharide confers polysaccharide rigidity and immunodominance by masking additional epitopes.

•The binding of anti-Vi mAb and polyclonal immune sera correlated with the level of O-acetylation.•C. freundii Vi resists de-O-acetylation and is more viscous than S. Typhi Vi.•Sera from human vaccine recipients contains IgG that recognizes the backbone of Vi.•Simulations show O-acetyls are exposed on the surface of Vi and confer rigidity.•MD gives conformational rationale for effect of O-acetylation on Vi antigenicity and viscosity.