After a campus outbreak of Neisseria meningitidis (meningococcal serogroup B), a devastating bacterial disease, which affected at least eight students at Princeton University

the US Food and Drug Administration approved the use of Bexsero to prevent the development of additional cases on that campus. Bexsero is considered to provide broader protective coverage than the US-licenced vaccines conventionally used against this disease. Which of the following methodologies was used to develop Bexsero?
a. conjugation of neisserial capsular polysaccharide to tetanus toxoid
b. reverse vaccinology
c. formalin treatment of secreted toxins
d. production of a combination vaccine that includes DTP plus a meningococcal polysaccharide diphtheria toxoid conjugate
e. engineering a nonpathogenic cattle strain of N. meningitidis to express antigens associated with pathogenic human strains.


Rationale: The correct answer is b. Reverse vaccinology was the novel technique used to develop Bexsero®. The genome of Neisseria meningitidis strain MC58 was used to identify candidate proteins that not only were exposed on the bacterial surface or secreted but were also conserved across many different pathogenic strains. Four such candidate proteins were identified, including factor H binding protein (fHbp); Neisseria heparin-binding antigen (NHBA); neisserial adhesin A (NadA); and porin A (PorA). The vaccine consists of all four components. There are conjugate vaccines available (for example Menactra®), but Bexsero is not a conjugate vaccine. There are no toxoid-only vaccines for meningococcal disease. Finally, there are no known cattle strains of N. meningitidis, which is a strictly human pathogen.

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