About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question: Should persons vaccinated with a serogroup B meningococcal (MenB) primary series who are at increased risk for serogroup B meningococcal disease during an outbreak receive a MenB booster dose?
Population: Persons aged ≥10 years who have previously completed a MenB-FHbp or MenB-4C primary series who are at increased risk for serogroup B meningococcal disease during an outbreak of serogroup B meningococcal disease
Intervention: MenB-FHbp or MenB-4C booster dose
Comparison: No MenB-FHbp or MenB-4C booster dose
Outcome: Short-term immunogenicity of booster (critical), persistence of the immune response to the booster dose (important), serious adverse events from booster dose (critical)
Background
Meningococcal disease is a rare but severe infection that can progress rapidly. Among the 12 serogroups that cause disease, serogroups B, C, and Y are the most common in the United States. One in ten persons with meningococcal disease dies despite proper antibiotic treatment, and one in five survivors have long-term sequelae. The incidence of meningococcal disease has declined from 0.42 cases per 100,000 population in 2005 to 0.11 cases per 100,000 population in 2017. Serogroup B disease currently accounts for approximately 40% of U.S. cases.
Although incidence of meningococcal disease is low in the United States, outbreaks remain a public health concern due to the serious nature of Neisseria meningitidis infection. In 2015, the Advisory Committee on Immunization Practices (ACIP) recommended that adolescents and young adults aged 16-23 years may receive a MenB series based on individual clinical decision-making, with a preferred age of 16-18 years.12 Additionally, ACIP recommends that persons aged ≥10 years at increased risk for serogroup B meningococcal disease, including those at increased risk during a serogroup B outbreak, receive a MenB primary series.123 Available evidence suggests that antibodies wane in the years following completion of the primary series. Thus, a MenB booster dose may be necessary to sustain protection in previously vaccinated persons who become at increased risk for meningococcal disease during a serogroup B outbreak.
The ACIP Meningococcal Vaccines Work Group assessed data related to potential benefits and harms of MenB booster doses in persons at increased risk during a serogroup B meningococcal disease outbreak. A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was completed for each MenB vaccine (MenB-FHbp and MenB-4C) to assess the certainty of evidence for a MenB booster dose (link). Additional factors related to MenB booster vaccination were assessed as part of the Evidence to Recommendations Framework (EtR), summarized below. GRADE and EtR for other persons at increased risk of meningococcal disease (e.g., person with certain underlying medical conditions and microbiologists routinely exposed to Neisseria meningitidis isolates) were completed separately and are presented elsewhere. Additional background information supporting the ACIP recommendations on the use of MenB booster doses can be found in the relevant publication of the recommendation referenced on the ACIP website.
Problem
Criteria | Work Group Judgments | Evidence | Additional Information |
---|---|---|---|
Is the problem of public health importance? | Yes | Serogroup B meningococcal disease outbreaks are an important public health concern in the United States:
Serogroup B outbreaks are rare in the United States, but disproportionately affect college students:
From 2013–2018, 11 college-based outbreaks (41 cases and 2 deaths) were reported.5 Conclusion: Serogroup B meningococcal disease outbreaks are a public health concern that have disproportionately affected college students in recent years. |
College students are the primary group at increased risk for serogroup B outbreaks who may have previously received a MenB primary series as a healthy adolescent. |
Benefits and Harms
References in this table:67891011121314151617
Criteria | Work Group Judgments | Research Evidence | Additional Information |
---|---|---|---|
How substantial are the desirable anticipated effects? | Large | A MenB booster dose elicits robust short-term immunogenicity:
Persistence of the immune response to MenB booster doses is sufficient to provide protection to persons at short-term increased risk of exposure during an outbreak:
Limited data are available on vaccine effectiveness or duration of protection of MenB vaccines in adolescents or adults:
Conclusion: MenB booster doses elicit a robust immune response; persistence appears to exceed that of a primary series (likely 2–3 years). No data on effectiveness of a MenB booster doses are available. However, based on the limited data available on the primary series, booster vaccinations are expected to be effective for the short-term protection against serogroup B disease during an outbreak. |
No consistent evidence todate that MenB vaccines reduce or prevent serogroup B meningococcal carriage; therefore, herd immunity is unlikely. |
How substantial are the undesirable anticipated effects? | Minimal | Clinical trials for MenB boosters demonstrated an acceptable safety profile:
Although clinical trials assessing safety of MenB booster doses are limited due to the small size of study population, clinical trials and post-marketing safety surveillance including over 69,000 healthy adolescents and adults have demonstrated the safety of a MenB-FHbp and MenB-4C primary series. 13-17
Conclusion: Given the acceptable safety profile observed during clinical trials and observational studies for MenB booster doses, as well as that observed during clinical trials and post-marketing safety surveillance of the primary series, undesirable effects of MenB boosters are likely to be minimal. |
All studies related to safety of MenB booster doses had a small number of enrolled subjects; rare adverse events may not have been detected. |
Do the desirable effects outweigh the undesirable effects? | Favors intervention | MenB booster dose in persons at increased risk of meningococcal disease during an outbreak is favored as an intervention due to:
Conclusion: The desirable effects of a MenB booster dose in this population outweighs the undesirable effects. |
|
What is the overall certainty of this evidence for the critical outcomes? | Certainty of the evidence on effectiveness is Level 4 (Very low)
Certainty of the evidence on safety is Level 4 (Very low) |
GRADE analysis was completed for each MenB vaccine to assess certainty of evidence.
MenB-FHbp:
MenB-4C:
See link to the associated GRADE tables for additional details. Conclusion: Overall certainty of evidence for effectiveness and safety of MenB booster doses in persons at increased risk during a serogroup B outbreak is very low. |
Values
References in this table:51516
Criteria | Work Group Judgments | Research Evidence | Additional Information |
---|---|---|---|
Does the target population feel that the desirable effects are large relative to undesirable effects? | Yes | All 11 universities that experienced serogroup B outbreaks during 2013–2018 implemented MenB primary series vaccination5, reflecting in part the target population’s value of the intervention.
Conclusion: Widespread implementation of MenB primary vaccination during university-based serogroup B outbreaks in the United States indicates that the target population values the intervention. |
|
Is there important uncertainty about or variability in how much people value the main outcomes? | Possibly important uncertainty or variability | Wide range in coverage of ≥1 MenB dose (14–98%)5 in 11 universities that implemented MenB primary vaccination during outbreaks of serogroup B meningococcal disease, regardless of university size, time since licensure of the vaccine, or number of cases in the outbreak, potentially indicates important uncertainty and/or variability in values of the target population.
Conclusion: Given variable rates of MenB vaccine uptake during college outbreaks, there may be important uncertainty and/or variability in how much people value the main outcomes. |
Additional factors unrelated to values (e.g., logistical/financial concerns, differences in student population15,16) may also have contributed to this range in MenB coverage. |
Acceptability
References in this table:1217181920
Criteria | Work Group Judgments | Research Evidence |
---|---|---|
Is the intervention acceptable to key stakeholders? | Yes | Following the availability of MenB vaccines in the United States, all universities that experienced serogroup B outbreaks implemented primary series vaccination as part of outbreak response, demonstrating acceptability of the intervention to:
Conclusion: MenB vaccination is acceptable to a wide variety of stakeholders. |
Resource Use
References in this table:182122
Criteria | Work Group Judgments | Research Evidence | Additional Information |
---|---|---|---|
Is the intervention a reasonable and efficient allocation of resources? | Yes | No cost-effectiveness analyses of a MenB booster dose during serogroup B outbreaks have been conducted. However, the strategy of mass vaccination of a MenB primary series for outbreak response is estimated to be more cost-effective than universal vaccination of all students at college entry.21
Experience demonstrates that MenB primary series mass vaccination during outbreaks requires substantial resources.18,22
The high costs incurred by universities may reflect the belief that vaccination with a MenB primary series in response to a serogroup B outbreak were a reasonable and efficient allocation of resources.
Conclusion: MenB booster vaccination is a reasonable and efficient allocation of resources given the serious nature of meningococcal disease infections and lack of more resource-efficient yet effective options to control serogroup B outbreaks. |
Feasibility
References in this table:18192324
Criteria | Judgments | Research Evidence | Additional Information |
---|---|---|---|
Is the intervention feasible to implement? | Yes | Serogroup B meningococcal disease outbreaks require intensive coordination, significant human resources, and action among multiple stakeholders to efficiently respond within a short time. 18,19,23,24
Low coverage of ≥1 MenB dose during some university-based serogroup B outbreaks may indicate feasibility concerns (e.g., programmatic, financial).18,24 As MenB vaccine products are not interchangeable, potential barriers to implementation include determining:
Despite challenging circumstances, universities have demonstrated the feasibility of conducting mass vaccination campaigns for the MenB primary series during outbreaks.
Conclusion: Although programmatic challenges to MenB booster doses are anticipated, the intervention is expected to be feasible based on successful implementation of MenB primary series campaigns during university outbreaks. |
A simplified HPV vaccine schedule is expected to be easier to explain and remember. |
Balance of Consequences
Desirable consequences clearly outweigh undesirable consequences in most settings.
Is there sufficient information to move forward with a recommendation? Yes
Recommendation
For persons at increased risk for serogroup B meningococcal disease during an outbreak, a one-time MenB booster dose is recommended if it has been at least 1 year since completion of a MenB primary series. A booster dose interval of ≥6 months may be considered by public health officials depending on the specific outbreak, vaccination strategy, and projected duration of elevated risk.
Additional considerations (optional)
Booster vaccination is only indicated for persons at increased risk for meningococcal disease during an outbreak, not for adolescents who previously received a MenB primary series as part of shared clinical decision-making and who are not at increased risk.
Additional guidance related to the programmatic implementation of MenB booster doses in persons at increased risk during a serogroup B outbreak will be addressed in revisions to CDC's Guidance for the Evaluation and Public Health Management of Suspected Outbreaks of Meningococcal Disease.
Final ACIP recommendation
ACIP recommends the intervention
ACIP considerations
Additional safety and effectiveness data on MenB booster doses will be necessary for the ongoing evaluation of this recommendation by ACIP.
This Evidence to Recommendation table is based on the GRADE Evidence to Decision framework developed through the DECIDE project. See further information. Framework last updated 19 June 2019.
View the complete list of EtR Frameworks
- MacNeil J. R. et al. (2015). "Use of Serogroup B Meningococcal Vaccine in Adolescents and Young Adults: Recommendation of the Advisory Committee on Immunization Practices, 2015". Morbidity and Mortality Weekly Report. 64 (41): 1171-1176.
- Patton M. E. et al. (2017). "Updated Recommendations Use of MenB-FHbp Serogroup B Meningococcal Vaccine – Advisory Committee on Immunization Practices, 2016". Morbidity and Mortality Weekly Report. 66 (19): 509-513.
- Folaranmi T. et al. (2015). "Use of Serogroup B Meningococcal Vaccines in Persons Aged ≥10 Years at Increased Risk for Serogroup B Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices, 2015". Morbidity and Mortality Weekly Report. 64 (22): 608-611.
- Mbaeyi S.A. et al. (2018). "Epidemiology of Meningococcal Disease Outbreaks in the United States, 2009-2013. Clinical Infectious Diseases 68 (4): 580-5.
- Soeters H.M. et al. (2019). "University-based serogroup B meningococcal disease outbreaks, United States, 2013-2018. Emerging Infectious Diseaseshttps://doi.org/10.3201/eid2503.181574
- Balmer P. et al. “Immunogenicity and safety of a MenB-FHbp booster dose.” Advisory Committee on Immunization Practices Meeting, February 28, 2019.
- Nolan T. et al. (2019). "Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine." Vaccine. https://doi.org/10.1016/j.vaccine.2018.12.059
- Szenborn L. et al. (2018). "Immune Responses to Booster Vaccination with Meningococcal ABCWY Vaccine After Primary Vaccination with Either Investigational or Licensed Vaccines." Pediatric Infectious Diseases Journal 37: 475-482.
- Argante L. et al. (2019). "Modeling of long-term antibody persistence following 4CMenB vaccination in Adolescents." 15th Congress of the European Meningococcal and Haemophilus Disease Society. Lisbon, Portugal.
- Institut National de Sante Publique du Québec. (2018). "Epidemiologic Impact of the vaccination campaign against serogroup B meningococcal disease in the Saguenay-Lac-Saint-Jean Region in 2014."
- MenB-FHbp (Trumenba®) Package Insert. Revised 2018.
- MenB-4C (Bexsero®) Package Insert.
- Nolan T. et al. (2015). "Vaccination with a multicomponent meningococcal B vaccine in prevention of disease in adolescents and young adults." Vaccine 33: 4437-4445.
- Perez et J.L. al. (2018). "From research to licensure and beyond: clinical development of MenB-FHbp, a broadly protective meningococcal B vaccine." Expert Review of Vaccines 17 (6): 461-477.
- Fiorito T.M. et al. (2018). "Adverse Events Following Vaccination with Bivalent rLP2086 (Trumenba®): An Observational, Longitudinal Study During a College Outbreak and a Systematic Review. Pediatric Infectious Diseases Journal 37:e13-e19.
- Institut National de Sante Publique du Québec. (2018). "Epidemiologic Impact of the vaccination campaign against serogroup B meningococcal disease in the Saguenay-Lac-Saint-Jean Region in 2014."
- Duffy J. et al. (2017). "Safety of a meningococcal group B vaccine used in response to two university outbreaks." J Am Coll Health 65 (6): 380-388.
- Fisher E.A. et al. (2018). "Evaluation of Mass Vaccination Clinics in Response to a Serogroup B Meningococcal Disease Outbreak at a Large, Public University – Oregon, 2015." Journal of Adolescent Health 63: 151-156.
- Capitano B. et al. (2018). "Experience implementing a university-based mass immunization program in response to a Meningococcal B outbreak." Human Vaccines and Immunotherapeutics, DOI: 10.1080/21645515.2018.1547606
- Breakwell L. et al. (2016). "Understanding Factors Affecting University A Students' Decision to Receive an Unlicensed Serogroup B Meningococcal Vaccine." Journal of Adolescent Health 59: 457-464.
- Leeds I.L. et al. (2018). "Cost Effectiveness of Meningococcal Serogroup B Vaccination in College-Aged Young Adults." American Journal of Preventive Medicine. 000: 1-9.
- La E.M. et al. (2018). "Cost calculator for mass vaccination response to a U.S. college campus outbreak of serogroup B meningococcal disease." Human Vaccines and Immunotherapeutics, DOI: 10.1080/21645515.2018.1556074
- Ritscher A.M. et al. (2018). "Meningococcal serogroup B outbreak response University of Wisconsin-Madison." Journal of American College Health, DOI: 10.1080/07448481.2018.1469502
- Fiorito T.M. et al. (2017). "Rapid response to a college outbreak of meningococcal serogroup B disease: Nation's first widespread use of bivalent rLP2086 vaccine." Journal of American College Health, DOI: 10.1080/07448481.2017.1285772