However, says a study author, incomplete coverage "is a better idea than skipping vaccination altogether."
No immunologic response in one-third of those vaccinated
One-third of college students vaccinated for group B meningococcal disease during an outbreak on campus produced no immune response to the outbreak strain, though nearly all responded to the two strains included in the vaccine, researchers examining the December 2013 outbreak at Princeton University found.
Moreover, among the two-thirds who did develop antibody titers against the outbreak strain, many showed very weak responses, according to a report appearing Wednesday in the New England Journal of Medicine.
Of the students who received two doses of the 4CMenB (Bexsero) vaccine during the outbreak, 66.1% (95% CI, 32.9 to 81.6) were found to be seropositive (defined as hSBA titers >4) against Neisseria meningitidis serogroup B outbreak strain (M26313), reported Nicole E. Basta, PhD, of University of Minnesota in Minneapolis, and colleagues.
But this immune response was not exactly robust. Overall, geometric mean concentrations of antibody titers against the disease strain were low, even among students who had received two doses of the vaccine (7.6, 95% CI 6.7 to 8.5), the authors wrote.
With only about two-thirds of vaccinated students producing an immune response, that left 33.9% of vaccinated students who did not respond to the 4CMenB vaccine. In an interview with MedPage Today, Basta characterized this finding as "a bit surprising," but pointed out that the outbreak strain differed in some ways from the strains used to create the vaccine.
"I think receiving a vaccine that induces a response in a majority of people, even if not everyone develops an immune response to every strain of the pathogen, is really a better idea than skipping vaccination altogether," she said. "For many years, we didn't have any vaccines against meningococcal B disease in the U.S., so this is really a revolutionary development to now be able to protect against meningococcal B with a vaccine."
Two menB vaccines were recently approved by the FDA via an accelerated process: first, MenB-FHbp (Trumenba) in 2014 and 4CMenB (Bexsero) in 2015. Use of Bexsero was permitted for use during this outbreak prior to receiving FDA approval.
An accompanying editorial by Jerome H. Kim, MD, of International Vaccine Institute in Seoul, South Korea, commented on this accelerated approval process, which was not based on disease endpoints, but on an acceptable safety profile and lab biomarkers. He argued that this may be the case for vaccines against other infectious diseases, such as Zika, Ebola, and MERS in the future.
"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," Kim wrote. "4CMenB will not be the last vaccine for which a traditional, pivotal, double-blind, randomized, controlled trial with hard clinical endpoints is difficult, if not impossible, to generate."
For this study, Basta and colleagues examined blood samples from 607 students approximately 2 months following the outbreak, including those receiving two doses or one dose of the vaccine, as well as unvaccinated students. But overall, 93.2% of participants were vaccinated.
There were two strains used in the vaccine: 44/76-SL, which was closely related to the outbreak strain, and 5/99, which was a mismatch. In addition to testing for response to the outbreak strain, researchers also tested response to the vaccine reference strains. Nearly all students who received two doses of the vaccine produced an immune response to 44/76-SL and 5/99 (86.9% to 100% and 96.7% to 100%, respectively). Among these students, 87% to 100% who had an undetectable or low response to the outbreak strain produced an immune response to both reference strains.
"Interestingly, a subset of vaccinated students who did not meet titer thresholds did in fact become seropositive to the novel reference strains," Michelle Cespedes, MD, of Icahn School of Medicine at Mount Sinai in New York City told MedPage Today. "This suggests that the standard measure of vaccine response may not be an accurate measure of protection for this vaccine and the series may require a third dose." Cespedes was not involved with the research.
The CDC's Advisory Committee on Immunization Practices (ACIP) recently recommended (category A) routine vaccination against group B meningococcal disease for "high-risk groups" (such as areas with an active outbreak) of children ages 10 and older, and gave a permissive (category B) recommendation for the vaccine in persons ages 16 to 23 years.
"There definitely is a need for physicians to engage in more conversation about the risk of meningococcal disease," said Basta. "We've had a number of meningococcal disease outbreaks due to serogroup B at colleges and universities across the U.S. over the past several years, so clinicians really need to be familiar with ACIP guidelines issued this past year to effectively advise their patient populations about this disease because it really is a serious public health threat."
One limitation to the study is its observational nature -- as well as a small unvaccinated comparison group, due to the fact that it was conducted after an outbreak where the majority of students chose to be vaccinated.
Basta said that they are continuing to follow students who were involved in this outbreak to measure immune response in both vaccinated and unvaccinated students.
"With all new vaccines, we always want to take advantage of the opportunities we have to understand how broadly protective they are and how long the duration of protection lasts," she noted.
Basta received grant support from the Program on U.S. Health Policy at Princeton University and the Health Grand Challenge at Princeton University, a National Institutes of Health (NIH) Early Independence Award from the Office of the Director and a grant from the Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate of the Department of Homeland Security and the NIH Fogarty International Center.
Other co-authors report travel and other financial support from Pfizer, GlaxoSmithKline, Novartis and Sanofi Pasteur.
Cespedes disclosed financial relationships with Gilead Sciences.
Kim disclosed no relevant financial relationships.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner
last updated 07.21.2016
This article was first published on MedPage Today and reprinted with permission from UBM Medica. Free registration is required.