Why Was a Specific Meningococcal Disease Vaccine Recommended for the 2016 Rutgers Outbreak?

In the Spring 2016 semester, two undergraduates attending Rutgers University in New Brunswick, New Jersey, were diagnosed with serotype B meningococcal disease. In response to the outbreak, a rare thing happened: a specific vaccine brand, Trumenba, had been recommended to be administered to around 35,000 individuals at the university.

A research letter recently published in the Center for Disease Control and Prevention (CDC)’s Emerging Infectious Diseases journal offers insight into why that choice had been made.

When two undergraduates from the university were hospitalized due to suspected meningitis, using culture and slide agglutination, researchers in the New Jersey State Public Health Laboratory, based in Trenton, New Jersey, were able to identify serogroup B Neisseria meningitidis in cerebrospinal fluid specimens.

After sending the specimens to the CDC Bacterial Meningitis Laboratory, CDC researchers used real-time PCR to confirm that the isolates were, in fact, serogroup B N. meningitidis. Furthermore, using multilocus sequence typing, the researchers classified the isolates as clonal complex 11, sequence type 11, which, interestingly enough, is usually associated with serogroups C and W. Whole-genome sequencing revealed results that are arguably even more surprising: the isolates were found to be “genetically indistinguishable from one another, but different from all previously characterized meningococcal isolates in the United States.”

Currently, there are two vaccines available in the United States that are designed to protect against serogroup B meningococcal diseases: a two-dose series, MenB-4C, Bexsero, developed by GlaxoSmithKline Biologicals, Inc., and a 2- or 3-dose series, MenB-FHbp, Trumenba, developed by Pfizer, Inc. According to the research letter, when it comes to outbreak response, either of the drugs can usually be used. In fact, “in general, no brand preference exists.” But the CDC points out that the vaccines do target different antigens, which means that “they are not interchangeable; the same brand must be used for all doses.” In addition, the level of effectiveness of each vaccines depends on the specific strain responsible for the outbreak.

So, why was Trumenba specifically recommended for this outbreak? According to the letter, “Whole-genome sequencing identified a mismatch between the antigens in the outbreak strain and those targeted by Bexsero, prompting concern that Bexerso might not provide optimal protection against the outbreak strain.” They continued, “Although the outbreak strain antigens also did not exactly match those included in Trumenba, cross-protection with Trumenba was expected based on prior testing by the manufacturer.”

The strain isolates were then sent to an independent lab for further examination. Using flow cytometry, researchers found that the strain “had a low expression of factor H binding protein and low binding with antisera for the Neisserial heparin binding antigen included in Bexsero.” The researchers also used human complement (hSBA) to determine if serum that has been stored from healthy adults who had been previously vaccinated with either of the two vaccines could destroy the bacteria pertaining to the outbreak strain. Preliminary results suggested that either Bexsero or Trumenba would offer short-term protection against the strain. However, ultimately, they found that administering a third dose of Trumenba at 6 months after the first dose and 4 months after the second dose, “boosted hSBA titers against outbreak strain bacteria…for 9/9 persons 1 month after completion of the 3-dose series.” This means that a 3-dose series of Trumenba was expected to provide “the best and longest-lasting protection against the outbreak strain.”

Due to these findings, the New Jersey Department of Health and the university, with support from the CDC, recommended that the ~35,000 individuals at the university receive the 3-dose regimen of Trumenba.

“This recommendation for a specific brand of MenB vaccine was a rare exception to the general recommendation that either brand of MenB vaccine can help protect persons at increased risk during a serogroup B meningococcal disease outbreak,” authors of the letter remind the public. “The use of molecular and immunologic data as potential tools to inform meningococcal outbreak response requires further investigation before being routinely implemented,” they concluded.