FROM THE NEW ENGLAND JOURNAL OF MEDICINE
MenB-FHbp, a licensed meningococcal B vaccine that targets factor H-binding protein, a surface-exposed bacterial lipoprotein, has been shown to provide broad immunological protection against 4 primary and 10 additional strains of meningococcal B disease in teens and young adults, suggesting the potential to reduce the number of shots needed to protect this population, according to two phase 3 randomized, controlled, observer-blinded, multicenter trials.
The study involved two groups of subjects: one of teens, aged 10-18 years, and the other young adults, aged 18-25 years, who were randomized. The adolescent group underwent a 5:2:2:3 (MenB-FHbp lot 1,MenB-FHbp lot 2, hepatitis A vaccine, and saline) randomization. The young adult group randomization was not as complex, with a 3:1 randomization of MEN-B FHbp to saline. Patients received their injections at baseline, then they received another 2 months after the initial injection and then another 6 months after the initial injection. A hepatitis A vaccine was administered only to adolescents because of country-specific guidelines, but saline was used in the controls for both test groups.
After the third dose of MenB-FHbp, the percentage of patients whose antibody titers of serum bactericidal assays with human complement (hSBA) had increased by a factor of four rose as high as 78.8%-90.2% in adolescents and 78.9%-89.7% in young adults in the modified intention-to-treat population, depending on which strain was tested. This population was made up of randomized patients who had at least one valid and determinate assay. Among participants, 82% of adolescents and 84.5% of young adults had the composite response, which was defined as the proportion of patients who had an hSBA titer response that reached or exceeded the limit of quantitation for all primary test strains combined at 1 month after the third MenB-FHbp vaccine dose was administered.
Using the hSBA responses to the primary strains, a positive predictive value analysis predicted the immune responses to other meningitis strains with H-binding protein. For subfamily A strains among adolescents, the positive predictive values for patient responses were 64.4%-100% after dose 2 and 75.6%-99.6% after dose 3. Among young adults, the positive predictive values after dose 2 and 3 were 61.6%-100% and 72.2%-100%, respectively.
A similar pattern was observed for subfamily E strains. Among adolescents the positive predictive values for patient responses were 78.9%-100% and 86.4%-99.6% after doses 2 and 3, respectively. Young adults also had high positive predictive values after doses 2 and 3, with values of 70%-100% and 80.5%-98.8%, respectively.
Injection site reactions and systemic events were both observed in response to MenB-FHbp in both adolescents and young adults. The most common injection site reaction was pain, which often occurred occurring after the first dose. Six adolescents and three young adults, one of whom received a saline injection, withdrew from the study because of injection site reactions. The most common systemic events among adolescents were headaches and fatigue. The events that caused patients to withdraw were associated with fever, chills, and mild arthralgia and moder myalgia.
“By demonstrating with positive–predictive value analyses the ability of 4 primary test strains to predict coverage with the use of 10 additional test strains, our findings provide assurance that observed immune responses to the primary strains are representative and indicative of vaccine responses to diverse disease-causing meningococcal B strains,” wrote Lars Ostergaard, MD , of the Aarhus (Denmark) University Hospital and his colleagues.
The studies were supported by Pfizer, and all researchers reported having received various forms of support from that company. Although many of the researchers hold patents, or have patents pending, that are relevant to these studies, they had no other.
SOURCE: Ostergaard L et al. N Engl J Med. 2017 Dec 14;377(24):2350-62 .
