A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults

N Engl J Med. 2017 Dec 14;377(24):2349-2362. doi: 10.1056/NEJMoa1614474.


Background: MenB-FHbp is a licensed meningococcal B vaccine targeting factor H-binding protein. Two phase 3 studies assessed the safety of the vaccine and its immunogenicity against diverse strains of group B meningococcus.

Methods: We randomly assigned 3596 adolescents (10 to 18 years of age) to receive MenB-FHbp or hepatitis A virus vaccine and saline and assigned 3304 young adults (18 to 25 years of age) to receive MenB-FHbp or saline at baseline, 2 months, and 6 months. Immunogenicity was assessed in serum bactericidal assays that included human complement (hSBAs). We used 14 meningococcal B test strains that expressed vaccine-heterologous factor H-binding proteins representative of meningococcal B epidemiologic diversity; an hSBA titer of at least 1:4 is the accepted correlate of protection. The five primary end points were the proportion of participants who had an increase in their hSBA titer for each of 4 primary strains by a factor of 4 or more and the proportion of those who had an hSBA titer at least as high as the lower limit of quantitation (1:8 or 1:16) for all 4 strains combined after dose 3. We also assessed the hSBA responses to the primary strains after dose 2; hSBA responses to the 10 additional strains after doses 2 and 3 were assessed in a subgroup of participants only. Safety was assessed in participants who received at least one dose.

Results: In the modified intention-to-treat population, the percentage of adolescents who had an increase in the hSBA titer by a factor of 4 or more against each primary strain ranged from 56.0 to 85.3% after dose 2 and from 78.8 to 90.2% after dose 3; the percentages of young adults ranged from 54.6 to 85.6% and 78.9 to 89.7%, after doses 2 and 3, respectively. Composite responses after doses 2 and 3 in adolescents were 53.7% and 82.7%, respectively, and those in young adults were 63.3% and 84.5%, respectively. Responses to the 4 primary strains were predictive of responses to the 10 additional strains. Most of those who received MenB-FHbp reported mild or moderate pain at the vaccination site.

Conclusions: MenB-FHbp elicited bactericidal responses against diverse meningococcal B strains after doses 2 and 3 and was associated with more reactions at the injection site than the hepatitis A virus vaccine and saline. (Funded by Pfizer; ClinicalTrials.gov numbers, NCT01830855 and NCT01352845 ).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / blood*
  • Bacterial Proteins / blood*
  • Child
  • Female
  • Fever / etiology
  • Humans
  • Intention to Treat Analysis
  • Male
  • Meningococcal Infections / immunology
  • Meningococcal Infections / microbiology
  • Meningococcal Infections / prevention & control*
  • Meningococcal Vaccines / adverse effects
  • Meningococcal Vaccines / immunology*
  • Neisseria meningitidis, Serogroup B* / genetics
  • Neisseria meningitidis, Serogroup B* / immunology
  • Phylogeny
  • Single-Blind Method
  • Young Adult


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Meningococcal Vaccines
  • factor H-binding protein, Neisseria meningitidis

Associated data

  • ClinicalTrials.gov/NCT01830855
  • ClinicalTrials.gov/NCT01352845
  • ClinicalTrials.gov/NCT01830855
  • ClinicalTrials.gov/NCT01352845