Colonization of the nasopharyngeal mucosa by meningococcus and other polysaccharide (PS)-encapsulated bacteria precedes invasion. PS-conjugate vaccines induce PS-specific B-cell memory (BMEM) and also prevent colonization, thus blocking person-to-person transmission, generating herd protection. However, in isolation the BMEM are unable to sustain immunity. Furthermore, the duration of herd protection the vaccines induce appears limited. We demonstrate that, despite the persistence of PS-specific BMEM, the population is not maintained within the nasopharynx. Although booster immunization results in the transient appearance of PS-specific BMEM within the mucosa, this reflects the re-circulation of systemic BMEM through the site rather than the generation of resident mucosal BMEM. The induction of sustained PS-specific BMEM in the nasopharynx would allow the population to be activated by colonization, thus inhibiting subsequent invasion. It would also be expected to boost local mucosal immunity, thus extending herd protection. Strategies to generate PS-specific BMEM in the mucosa warrant further investigation.
Bibliographical noteFunding Information:
We gratefully acknowledge the help of all the subjects enrolled in this study and to Novartis for donating the Men ACWY vaccine used in parts of the work. This study was funded by the David Baum Trust.