The Recommended Use of the Multicomponent Meningococcal B (4CMenB) Vaccine in Canada

Prepared by: Meningococcal B Pilot Project Task Group

March 26, 2014

Executive Summary

Table of Contents

• Introduction
• Methods
• Epidemiology
• Recommendations
  • Who should receive this vaccine?
  • Should this vaccine be included in the routine immunization schedule?
• Conclusion

Introduction

In Canada, four serogroups, B, C, W-135, and Y of the bacteria Neisseria meningitidis are responsible for the majority of invasive meningococcal disease (IMD), with incidence varying by the meningococcal serogroup, individual age groups, geographic area, and the time of year. In recent years, the incidence of serogroup C has declined significantly due to the introduction of meningococcal C conjugate vaccine into routine immunization programs.

Vaccination is the most effective measure for preventing IMD. Bexsero^® (Novartis Vaccines) is a novel multicomponent meningococcal serogroup B (4CMenB) vaccine. The 4CMenB is the first vaccine to prevent invasive disease due to serogroup B, and has been created through a process of reverse vaccinology. Through this process potential vaccine targets (i.e., antigens) are identified and developed by sequencing the meningococcal serogroup B genome.

The following are the recommendations for the use of the 4CMenB vaccine in Canada as developed by the Meningococcal B Pilot Project Task Group (MBPPTG) and approved by the National Advisory Committee for Immunization (NACI) and endorsed by the Public Health Network.

Methods

In June 2012, based on a proposal from the National Immunization Strategy Task Group (NIS-TG), the Communicable and Infectious Disease Steering Committee (CID-SC) approved the creation of a new, time-limited MBPPTG. This task group was mandated to develop guidance for use of meningococcal B vaccine by integrating scientific and technical recommendations with program and policy recommendations.

A comprehensive literature search and review was completed to identify relevant evidence on the 4CMenB vaccine including safety, immunogenicity, efficacy, and effectiveness of the vaccine, vaccine schedules, target populations, and other aspects of the overall immunization strategy. In addition, the burden due to IMD in Canada was reviewed. Following critical appraisal of individual studies, summary tables with ratings of the quality of the evidence were prepared using NACI's methodological hierarchy. After a thorough review of the evidence and consultations, the MBPPTG proposed provisional recommendations, pending achievement of the Notice of Compliance for market authorization in Canada. The full knowledge synthesis and review is maintained by the Public Health Agency of Canada (the Agency).

Using the analytic framework for immunization program in Canada, the following chapters were developed and completed based on the NACI Statement to support programmatic considerations:

• Immunization Strategies
• Social and Economic Cost and Benefits
• Program Feasibility and Acceptability
• Program Evaluation and Research
• Other Considerations
• Recommended Immunization Program

The full knowledge synthesis and literature review for the acceptability, feasibility and ethical considerations for vaccination against serogroup B meningococcus is maintained by the Agency.

The NACI Statement, presented as Part 1, and the immunization programmatic chapters, presented as Part 2, have been combined together and are considered the Common Guidance for the recommended use of the multicomponent meningococcal B (4CMenB) vaccine in Canada.

Epidemiology

With the declining incidence of serogroup C, serogroup B now makes up the greatest proportion of reported IMD cases in Canada (62% due to serogroup B versus 2% due to serogroup C in 2011). Between 2007 and 2011, an average of 111 cases of serogroup B IMD were reported annually in Canada. From 2007 to 2011, serogroup B incidence has fluctuated slightly between 0.27 and 0.40 cases per 100,000 per year.

Figure 1 - Incidence of IMD (per 100,000 population) in Canada by serogroup and year, from 1995 to 2011

Enlarge Figure 1

The incidence of serogroup B is low and remains highest in infants less than one year of age with an age-specific incidence rate of 5.8 cases per 100,000 in 2011, followed by one to four year olds (1.4 cases per 100,000) and 15 to 19 year olds (0.7 cases per 100,000). Although serogroup B incidence rates follow similar trends across provinces and territories, the incidence of serogroup B among 15 to 19 year olds has been particularly high in Québec compared to other regions (2.6 cases per 100,000 in 2011).

Recommendations

In developing the recommendations, NACI and MBPPTG considered the burden of illness from IMD, the safety and immunogenicity of the newly authorized 4CMenB vaccine, as well as other aspects of overall immunization strategies. MBPPTG further considered social and economic cost benefits, acceptability, feasibility, equity, ethical, and political considerations.

Recommendations of NACI and MBPPTG for the use of the multicomponent meningococcal B vaccine in Canada are limited by the lack of evidence and the range of uncertainty of the underlying assumptions, particularly those concerning vaccine's coverage of circulating strains, herd immunity, effectiveness and potential adverse effects of vaccination at the population level. These recommendations will be updated at the time new data becomes available. Epidemiological, economic and other local programmatic/operational factors will be considered by provinces and territories when deciding on the inclusion of the following recommendations in publicly funded immunization programs.

Who should receive this vaccine?

Immunization of individuals (≥2 months of age) should be considered under the following circumstances:

• If they are at high risk of meningococcal disease caused by serogroup B N. meningitidis.
• If they have been in close contact with a case of IMD caused by serogroup B N. meningitidis.
• If they are at risk during IMD outbreaks caused by serogroup B N. meningitidis or the emergence of hyperendemic and/or hypervirulent N. meningitidis strains that are predicted to be susceptible to the vaccine based on Meningococcal Antigen Typing System (MATS) testing.

The 4CMenB vaccine is contraindicated in individuals with a serious allergy to any vaccine component or previous dose.

There are no studies of 4CMenB vaccine in the following populations:

• pregnant or lactating women,
• infants less than 2 months of age,
• individuals over 55 years of age,
• individuals with a chronic medical condition,
• those who have had a previous meningococcal infection.

Should this vaccine be included in the routine immunization schedule?

Currently, it is not recommended to include the multicomponent meningococcal serogroup B (4CMenB) vaccine in routine immunization programs for Canadian infants, children, adolescents and adults.

Conclusion

The scientific evidence regarding the novel multicomponent meningococcal serogroup B (4CMenB) vaccine Bexsero^® has been reviewed in order to provide medical, scientific, and public health advice on the use of the vaccine in the Canadian population.

Given the current available information on the burden of IMD in Canada, as well as the lack of evidence and the range of uncertainty of the underlying assumptions, particularly those concerning the predicted level of strain susceptibility, duration of protection, impact on meningococcal carriage and herd immunity, and potential adverse effects of vaccination at the population level, a recommendation for the implementation of a routine immunization program for meningococcal serogroup type B in Canada cannot be made at this time.

Future research and surveillance activities should address the potential of 4CMenB vaccine to protect against Canadian meningococcal B strains and other meningococcal serogroups, as well as address issues around vaccine safety, vaccine efficacy, duration of protection, herd immunity, carriage, special populations and surveillance needs.