The Use of Bivalent Factor H Binding Protein Meningococcal Serogroup B (MenB-fHBP) Vaccine for the Prevention of Meningococcal B Disease

1. What
Invasive meningococcal disease
Invasive meningococcal disease (IMD) usually presents as an acute febrile illness with rapid onset and features of meningitis or septicemia (meningococcemia), or both, and a characteristic non-blanching rash. Overall case fatality is approximately 10%, and up to a third of survivors may have long term sequelae, which include hearing loss, neurologic disabilities, and digit or limb amputations. From 2012 to 2016, a total of 353 of 583 (60.5%) reported cases of IMD in Canada were due to serogroup B. The highest rate of infection occurs in infants <1 year of age. The rates of IMD from other serogroups have been decreasing since the introduction of routine programs using conjugate polysaccharide vaccines. Additional information about IMD is available on the Government of Canada web site (Invasive Meningococcal Disease).

Bivalent factor-H binding protein meningococcal serogroup B (MenB-fHBP) vaccine (Trumenba®)
The bivalent factor-H binding protein meningococcal serogroup B (MenB-fHBP) vaccine was authorized for use in Canada in October 2017 for the prevention of IMD caused by N. meningitidis serogroup B in individuals 10–25 years of age. The MenB-fHBP vaccine is immunogenic, although its effectiveness, impact on carriage and herd immunity, and its duration of protection remain unknown.

2. Who
Groups recommended for immunization
NACI makes the following general recommendations and guidance and recommendations for public health program level and individual level decision-making.

General recommendations and Guidance
General guidance: NACI continues to recommend immunization against serogroup B IMD to all individuals who are at a higher risk of disease due to an underlying medical condition or at an increased risk of exposure. However, the two serogroup B meningococcal vaccines currently authorized for use in Canada (MenB-fHBP and 4CMenB) are not interchangeable, as they contain different antigens and there are no published studies on the immunogenicity resulting from a vaccination series combining the two products. Therefore, the same vaccine product should be used for all doses in a vaccination series. If, in a person with an incomplete vaccination series, it is unknown what vaccine product they initially received, the initial dose(s) should be discounted and the vaccination series repeated using the same vaccine product for all doses in the new, repeated series.

Recommendations for Public Health Program Level Decision-making
(I.e., provinces/territories making decisions for publicly funded immunization programs)

Recommendation 1: NACI recommends that the MenB-fHBP vaccine should not be offered in routine universal immunization programs in Canada at this time. (Strong NACI Recommendation)

NACI concludes there is insufficient evidence to recommend routine universal immunization (Grade I Evidence).
Recommendation 2a: NACI recommends that a serogroup B meningococcal vaccine (MenB-fHBP or 4CMenB) should be offered in jurisdictions experiencing serogroup B meningococcal disease outbreaks or with the emergence of hyperendemic N. meningitidis strains that are predicted to be susceptible to the vaccine. (Strong NACI Recommendation)

NACI concludes there is fair evidence to recommend vaccine use during outbreaks (Grade B Evidence).
Recommendation 2b: NACI recommends that the MenB-fHBP vaccine may be considered as an option for use in individuals 10 years of age and older in such circumstances. (Discretionary NACI Recommendation)

NACI concludes there is insufficient evidence of the MenB-fHBP vaccine use in such circumstances (Grade I Evidence); therefore, this recommendation is based on expert opinion.
Recommendation 3a: NACI recommends that a serogroup B meningococcal vaccine (MenB-fHBP or 4CMenB) should be offered, in addition to chemoprophylaxis, for protection of individuals who are close contacts with a case of invasive meningococcal disease caused by serogroup B Neisseria meningitidis. (Strong NACI Recommendation)

NACI concludes there is insufficient evidence of vaccine effectiveness in close contacts of cases of IMD (Grade I Evidence); therefore, this recommendation is based on expert opinion.
Recommendation 3b: NACI recommends that the MenB-fHBP vaccine may be considered as an option for use in individuals 10 years of age and older who are close contacts with a case of IMD caused by serogroup B Neisseria meningitidis. (Discretionary NACI Recommendation)

NACI concludes there is insufficient evidence of the MenB-fHBP vaccine use in close contacts (Grade I Evidence); therefore, this recommendation is based on expert opinion.
Recommendation 4a: NACI recommends that a serogroup B meningococcal vaccine (MenB-fHBP or 4CMenB) should be offered for the active immunization of individuals with underlying medical conditions that would put them at higher risk of meningococcal disease than the general population to reduce the risk of invasive serogroup B meningococcal disease. (Strong NACI Recommendation)

NACI concludes there is insufficient evidence of vaccine use in high-risk populations (Grade I Evidence); therefore, this recommendation is based on expert opinion.
Recommendation 4b: NACI recommends that the MenB-fHBP vaccine may be considered as an option for use in high-risk individuals 10 years of age and older, in a 3-dose schedule (0, 1-2, 6 months), to reduce the risk of invasive serogroup B meningococcal disease. (Discretionary NACI Recommendation)

NACI concludes there is insufficient evidence of the MenB-fHBP vaccine use in high-risk populations (Grade I Evidence); therefore, this recommendation is based on expert opinion.
For Individual Level Decision-making (i.e., individuals wishing to prevent serogroup B IMD or clinicians wishing to advise individual patients about preventing this outcome with vaccines that may not be currently included in publicly funded immunization programs; and organizations or decision makers responsible for programs offering vaccine services to various groups including individuals at risk of acquiring this outcome)

Recommendation 5a: NACI recommends that a serogroup B meningococcal vaccine (MenB-fHBP or 4CMenB) should be offered for the active immunization of individuals at higher risk of exposure to serogroup B meningococcal isolates than the general population to reduce the risk of invasive serogroup B meningococcal disease. (Strong NACI Recommendation)

NACI concludes there is insufficient evidence of vaccine use in high-risk populations (Grade I Evidence); therefore, this recommendation is based on expert opinion.
Recommendation 5b: NACI recommends that the MenB-fHBP vaccine may be considered as an option for use in such high-risk individuals 10 years of age and older, in a 2-dose schedule (0, 6 months), to reduce the risk of invasive serogroup B meningococcal disease. (Discretionary NACI Recommendation)

NACI concludes there is insufficient evidence of the MenB-fHBP vaccine use in high-risk populations (Grade I Evidence); therefore, this recommendation is based on expert opinion.
Recommendation 6: NACI recommends that the MenB-fHBP vaccine may be considered as an option for individuals 10-25 years of age who are not at higher risk of meningococcal disease than the general population, in a 2-dose schedule (0 and 6 months), to reduce the risk of invasive serogroup B meningococcal disease. (Discretionary NACI Recommendation)

NACI concludes there is fair evidence of vaccine immunogenicity to recommend the MenB-fHBP vaccine when given according to the schedule used during clinical trials (Grade B Evidence).
3. How
The vaccine is supplied in a single-dose, prefilled syringe. Doses of MenB-fHBP should be administered as intramuscular injections only, preferably in the deltoid muscle.

The vaccine is authorized for use in two immunization schedules. The standard schedule for routine immunization is two doses (0.5 mL per dose) administered at 0 and 6 months. For persons at increased risk of IMD, there is a three-dose schedule (0.5 mL per dose) administered at 0 month followed by a second dose at least one month later, followed by a third dose at least 4 months after the second dose. The need for a booster dose following the primary immunization series has not been established.

MenB-fHBP should be refrigerated at 2 °C to 8 °C. The vaccine should be discarded if it has been frozen.

Contraindications to administration of the vaccine include hypersensitivity to the vaccine or any of its components. A severe allergic reaction to any previous dose of the vaccine or to any of its components is also a contraindication to MenB-fHBP administration. There are no data available on the use of MenB-fHBP in immunocompromised individuals or in pregnant women. It is also not known whether MenB-fHBP is excreted in human breast milk.

The safety and efficacy of the vaccine have not been established in children less than 10 years of age. The vaccine has also not been studied in older adults (>65 years).

The vaccine can be given concomitantly with quadrivalent human papillomavirus vaccine; meningococcal serogroup A, C, Y, W conjugate vaccine; and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed. The concomitant administration of MenB-fHBP has not been studied with other vaccines. If MenB-fHBP is to be administered concomitantly with another vaccine, a separate injection site and a different syringe must be used for each injection.

4. Why
Although the incidence of IMD is low, outbreaks can occur and people with certain medical conditions are at greater risk of disease than the general population. Serogroup B is now responsible for the majority of IMD cases in Canada. The overall case fatality rate of invasive meningococcal disease (IMD) is approximately 10% and up to a third of survivors may have long term sequelae, which include hearing loss, neurologic disabilities, and digit or limb amputations.