Background. Nasopharyngeal carriage of meningococcus or related species leads to protective immunity in adolescence or early adulthood. This natural immunity is associated with mucosal and systemic T cell memory. Whether parenteral Neisseria meningitidis serogroup B (MenB) vaccination influences natural mucosal immunity is unknown. Objectives. To determine whether parenteral MenB vaccination affects mucosal immunity in young adults and whether this immunity differs from that induced in the blood. Methods. Otherwise healthy volunteers were immunized with MenB outer membrane vesicle vaccine before and after routine tonsillectomy. Mucosal and systemic immunity were assessed in 9 vaccinees and 12 unvaccinated control subjects by measuring mononuclear cell proliferation, cytokine production, Th1/Th2 surface marker expression, and antibody to MenB antigens. Results. Parenteral vaccination induced a marked increase in systemic T cell immunity against MenB and a Th1 bias. In contrast, although mucosal T cell proliferation in response to MenB neither increased nor decreased following vaccination, mononuclear cell interferon γ, interleukin (IL)-5, and IL-10 production increased, and the Th1/Th2 profile lost its Th1 bias. Conclusions. Parenteral MenB vaccination selectively reprograms preexisting naturally acquired mucosal immunity. As new-generation protein-based MenB vaccine candidates undergo evaluation, the impact of these vaccines on mucosal immunity in both adults and children will need to be addressed.
Bibliographical noteFunding Information:
Potential conflicts of interest: V.D. and J.F. have received assistance for the purpose of attending scientific meetings from Novartis Vaccines. R.B. has received assistance to attend scientific meetings from Wyeth Vaccines and Baxter Bioscience and has served as a consultant for GlaxoSmithKline, Fujisawa GmbH, Sanofi Pasteur, and Baxter Bioscience. Industry honoraria received for consulting, lecturing, and writing are paid directly into Central Manchester and Manchester Children’s University Hospitals National Health Service Trust endowment fund. R.B. has performed contract research on behalf of the Health Protection Agency (funded by Wyeth Vaccines, Novartis, Baxter Bioscience, GlaxoSmithKline, Sanofi Pasteur, Fujisawa GmbH, Alexion Pharmaceuticals, Microscience, and Xenova Research). P.O. is an employee of Norvartis Vaccines. L.M.N. is an employee of the Norway National Institute of Public Health.
Financial support: Meningitis Trust ( grant 0020–5650 to R.S.H., N.A.W., and R.B.); Royal College of Surgeons (grant VRF02/03 to C.G.H.); Meningitis Research Foundation (grant 12a/00/02 to N.A.W. and R.S.H.); Wellcome Trust (a Value in People award to V.D.).