In the Journals: A Field Trial of a Meningococcal B Vaccine

From March 2013 through March 2014, a meningococcal serogroup B (MenB) outbreak occurred at Princeton University; nine students were affected, including one who died. The Princeton outbreak wasn’t unique; between 2009 and 2015, seven outbreaks of MenB occurred in U.S. universities that resulted in 43 cases and three deaths.

At the time of the Princeton outbreak, the FDA had not yet licensed MenB vaccine for the United States; however, a licensed vaccine (Bexsero®, GlaxoSmithKline) had been used elsewhere. Although Bexsero wasn’t yet licensed in the U.S., the CDC, under a compassionate use protocol, offered vaccine to 6,000 students beginning in December 2013. Within six months, 95 percent of eligible students had received at least one dose and 89 percent had completed the two-dose series.

In July 2016, Nicole Basta and coworkers reported immunogenicity studies from students who received Bexsero during the Princeton outbreak (Basta N, Mahmoud A A F, Wolfson J, et al. Immunogenicity of a Meningococcal B Vaccine during a University Outbreak. N Engl J Med. 2016 Jul 21;375(3):220-8)). Using an assay that detects bactericidal antibodies, these researchers found that only 66.1 percent of vaccine recipients developed what would have been considered a protective immune response against the strain of bacteria that was circulating at Princeton. Of interest, 86.9 and 100 percent of vaccinated students developed protective immune responses against two reference strains. These data support the fact that there is substantial genetic and antigenic diversity among MenB isolates.

It should be noted that none of the vaccinated students, including those who did not develop a detectable, protective immune response, developed MenB disease. Nonetheless, these data raise an interesting question about whether the two-dose schedule for Bexsero is the best one. The authors state, “Our findings raise the questions about whether a third dose of [Bexsero] might increase the proportion of seropositive responses against strains that were not perfectly matched to the vaccine. The prelicensure study that reported the non-inferiority of two doses versus three doses of [Bexsero] and led to the two-dose recommendation involved vaccine reference strains only.”

The authors also reference a study that demonstrated the benefits of a third dose of Bexsero against mismatched strains (Findlow J, Bai X, Findlow H, et al. Safety and Immunogenicity of a Four-Component Meningococcal Group B Vaccine (4CMenB) and a Quadrivalent Meningococcal Group ACWY Conjugate Vaccine Administered Concomitantly in Healthy Laboratory Workers. Vaccine. 2015 Jun 26;33(29):3322-30.)

Taken together, these studies might lead to a change in the dosing schedules for MenB vaccines.