Meningitis B Vaccine Protection Lower Than Expected

Marcia Frellick

July 26, 2016

Analysis 3 years after the 2013 outbreak of Neisseria meningitidis B at Princeton University in New Jersey has found that the vaccine deployed fell short of expectations.

In 2013, the US Food and Drug Administration (FDA) granted special approval for use of a multicomponent meningococcal serogroup B (4CMenB) vaccine that was not yet licensed in the United States but had been licensed in Europe and Canada.

Data suggested that the vaccine (Bexsero, GlaxoSmithKline) would control the outbreak because isolates expressed antigens closely related to the vaccine antigens.

Nicole E. Basta, PhD, assistant professor in the School of Public Health at University of Minnesota in Minneapolis, and colleagues set out to quantify the immune responses induced by 4CMenB during the outbreak. Their results were published in the July 21 issue of the New England Journal of Medicine.

They found that 2 months after administration of the the second of the two doses, the level of protective immunity was lower than expected.

There was no evidence of a human serum bactericidal activity (hSBA) response against the outbreak strain in 33.9% of those vaccinated, although no cases of meningococcal disease caused by N meningitidis B were reported.

Among the 499 students who received both doses of the vaccine (10 weeks apart), 66.1% (95% confidence interval [CI], 61.8% - 70.3%) had putative protective immunity for the outbreak strain, although the geometric mean titer was low, at 7.6 (95% CI, 6.7 - 8.5). The researchers defined seropositivity as an hSBA titer of 4 or higher.

In a random subgroup of 61 people who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9% (95% CI, 75.8% - 94.2%) were seropositive for the closely related 44/76-SL strain.

These findings have implications for vaccination policies for preventing and controlling meningococcal B disease.

The authors write that it is possible that those who did not show evidence of protection against the outbreak strain, but who had an immune response to the antigens used to develop the vaccine, may benefit from some level of protection.

"Our findings also raise questions about whether a third dose of 4CMenB might increase the proportion of seropositive responses against strains that were not perfectly matched to the vaccine," the researchers write.

Other Serogroups Preventable

Although serogroups A, C, Y, and W N meningitidis are preventable with available vaccines, development of a serogroup B vaccine has been challenging.

In an accompanying editorial, Jerome H. Kim, MD, from the International Vaccine Institute in Seoul, South Korea, writes, "There is substantial genetic (and corresponding antigenic) diversity, and serogroup B meningococcal disease is both uncommon and in decline in countries where the burden is well understood. The incidence of meningococcal disease in the United States is at a historic low (0.18 per 100,000 person-years in 2013, including serotypes A, C, W, Y, and B)."

Dr Kim notes that more than 60,000 people have received at least one vaccination with 4CMenB in studies worldwide, and the safety profile for 4CMenB has been good.

"For a relatively uncommon but devastating infectious disease, the regulatory approval of a vaccine in the absence of ideal data may be necessary and appropriate if the vaccine is deployed in the context of a systematic public health response and if there is a commitment to the generation of additional information necessary for determining recommendations for use," he writes.

The FDA in 2015 approved 4CMenB and MenB-FHbp (Trumenba, Wyeth) for people aged 10 to 25 years via an expedited process intended for treating serious or life-threatening diseases with the caveat that postmarket studies of effectiveness would be needed.

Seven Outbreaks in 7 Years

In the United States, meningococcal disease represents a considerable public threat, especially to infants and young adults.

Between 2009 and 2015, there were seven meningococcal B outbreaks at US universities, and the 2013 to 2014 outbreak in New Jersey led to nine cases, including one death.

The authors conclude that further research is needed: "It is not yet known whether 4CMenB will induce sufficient immunity against diverse strains, especially during outbreaks," they write.

The study was supported by Princeton University, the National Institutes of Health, the Department of Homeland Security, and the National Institutes of Health Fogarty International Center. Several coauthors report support from GlaxoSmithKline, Novartis, Pfizer, and Sanofi Pasteur outside the submitted work. The editorialists have disclosed no relevant financial relationships.

N Engl J Med. 2016;375:220-228, 275-278. Article abstract, Editorial extract

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