Bacterial glycans coat such bacterial pathogens as Haemophilus influenzae and Group B streptococci. Covalent coupling of glycans with proteins to produce glycoconjugates form the basis of successful vaccines, but these vaccines can have variable efficacy in different populations. Avci et al. now investigate immune responses to glycoconjugates with a view to throwing light on such variation. They used the type III glycan of group B streptococci (GBSIII) linked to one of three different carrier proteins and a murine model. A combination of experiments demonstrated that the processed GBSIII (glycanp) is actually presented by MHCII when conjugated to a carrier protein or peptide. It was previously thought that only a processed peptide was presented by MHCII. The authors translate their findings into implications for vaccinologists, predicting that a processed GBSIII glycan-peptide with one peptide per eight repeating units of polysaccharide would increase the number of processed GBSIII glycan-peptides that could be presented from each molecule compared with an industry standard glycoconjugate. They go on to show that a GBSIII glycan vaccine rationally designed for greater efficacy elicits improved protection of mice from lethal streptococcal infection. This research could pave the way for rational design of glyco-polymers in other next-generation vaccines. (Nat. Med. 17, 1602–1609, 2011)