Discordant Effects of Licensed Meningococcal Serogroup B Vaccination on Invasive Disease and Nasal Colonization in a Humanized Mouse Model

Abstract

Background. The multicomponent meningococcal serogroup B vaccine (4CMenB) is an outer membrane vesicle and recombinant protein-based vaccine licensed to protect against serogroup B meningococcal disease. It remains unknown whether this vaccine will prevent carriage or transmission, key aspects in long-term vaccine success and disease eradication. Methods. Using a "humanized" transgenic mouse model of nasal colonization, we took a systematic approach to estimate the potential for carriage prevention against antigenically diverse Neisseria meningitidis strains and to compare this protection to an invasive meningococcal disease challenge model. Results. The 4CMenB vaccine prevented morbidity and mortality after lethal invasive doses of all meningococcal strains tested. Immunization effectively prevented carriage with only 1 of 4 single antigen-matched strains but reduced or prevented nasal colonization by all 4 isolates with multiple cross-reacting antigens. Each immunized mouse had substantial immunoglobulin G targeting the challenge strains, indicating that antibody correlates with protection against sepsis but not nasal carriage. Conclusions. Immunization with the 4CMenB vaccine elicits a robust humoral response that correlates with protection against invasive challenge but not with prevention of asymptomatic colonization. This suggests that widespread use of this vaccine will reduce morbidity and mortality rates in immunized individuals, with the potential to contribute to herd protection against a subset of strains.