Grading of Recommendations Assessment, Development, and Evaluation (GRADE): Use of Serogroup B 

Meningococcal (MenB) Vaccines in Adolescents and Young Adults (Including College Students)

Introduction

Two serogroup B meningococcal (MenB) vaccines have recently been licensed for use in the U.S. (MenBFHbp [Trumenba, Wyeth Pharmaceuticals, Inc.] and MenB-4C [Bexsero, Novartis Vaccines]). Both 

vaccines were approved for use in persons aged 10 through 25 years. MenB-FHbp was licensed as a 

three-dose series and MenB-4C was licensed as two-dose series. Evidence of benefits and harms were 

reviewed in accordance with GRADE methods (1). The primary policy question was “Should MenB 

vaccines be administered routinely to all adolescents and young adults (including college students)?” 

Methods for GRADE

The benefits outcomes considered for each vaccine included short-term immunogenicity (1 month after 

vaccination), persistence of immunogenicity (11–48 months after vaccination, if data available), and 

MenB immunogenicity with concomitant vaccines. The harms outcome considered for each vaccine 

included occurrence of serious adverse events (SAEs) after vaccination and safety of concomitant 

administration with other vaccines. 

Immunogenicity and safety data from five clinical trials (3 randomized controlled trials (RCT), 1 

randomized uncontrolled trial, and 1 immunogenicity extension study) of MenB-4C (2-6) and seven 

clinical trials (5 RCTs and 2 open label studies) of MenB-FHbp (7-10) (Pfizer, unpublished data) were

considered in the assessment. The evidence type for each outcome was derived through a review of 

study design, risk of bias, inconsistency, indirectness, imprecision and other considerations (strength of 

association, dose response gradient and opposing plausible residual confounding or bias). 

Estimates of short-term immunogenicity and persistence of immunogenicity (11–48 months after 

vaccination, if data available) were based on demonstration of immune response, as measured by 

human serum bactericidal activity (hSBA) against a small number of serogroup B strains. In studies 

supporting U.S. licensure, immunogenicity was assessed by the proportion of subjects who achieved a 

≥4-fold increase in hSBA titer for each of the strains tested, and the proportion of subjects who achieved 

a titer greater than or equal to the lower limit of quantitation (LLOQ) of the assay for all strains 

(composite response). The LLOQ was defined as the lowest amount of the antibody in a sample that can 

be reliably quantified. 

October 21, 2015

https://www.cdc.gov/vaccines/acip/recs/grade/menb-young-adults.pdf
Results:

Table 1a: Use of MenB-4C (Bexsero®) in adolescents and young adults (including college students): 

Evidence Table

Outcomes Design 

(# studies)

Initial 

Evidence

Risk of 

Bias

Inconsistency Indirectness Imprecision Publication 

Bias

Others Final 

Evidence

Overall 

Evidence 

Type

Benefits

Short-term 

immunogenicity

3 RCTs 1 Not 

Serious

Serious**

(-1)

Serious***

(-1)

Not Serious Unable to 

assess

Yes##

(+1)

2 2

1 Obs 3 Not 

serious

Not serious Serious***

(-1)

Not Serious Unable to 

assess

None 4

Persistence of 

immunogenicity 

(11-24 months)

2 RCTs 1 Serious*

(-1)

 Not 

serious

Serious***

(-1)

Not Serious Unable to 

assess

None 3 3

MenB

Immunogenicity 

with 

concomitant 

vaccination

No available studies

Harms

Serious Adverse 

Events

3 RCTs 1 Not 

serious

Not serious Not Serious Serious#

(-1)

Unable to 

assess

None 2 2

Safety with 

Concomitant 

vaccination 

(SAEs)

No available studies

Footnotes:

* No formal statistical hypothesis testing or sample size calculation planned in the protocol for one study. Potential selection bias for participants in the 

other study – downgraded by 1

** High heterogeneity, I-squared > 90% across all strains – downgraded by 1

*** Studies assessed correlate of protection and not directly efficacy – downgraded by 1

# The CI around the effect estimate includes both effect and non-effect – downgraded by 1

## Strong strength of association. RR ranges between 4.44 and 5.19 – upgraded by 1

Table 1b: Considerations for Vaccine Use: MenB-4C (Bexsero®)

Key Factors Comments

Balance between benefits 

and harms

Among healthy adolescents and young adults (including college 

students), the vaccine is immunogenic in the short-term and 

persists 1-2 years after vaccination. Low disease burden lowers 

overall benefits.

Evidence type for benefits and harms

MenB-4C vaccine use 

among healthy 

adolescents and young 

adults (including college 

students) 

Benefits:

Short-term immunogenicity: Evidence Type 2

Persistence in immunogenicity (11-24 months): Evidence Type 3

MenB immunogenicity with concomitant vaccination: Not 

assessed

Harms:

Serious Adverse Events: Evidence Type 2

SAEs following concomitant vaccination: Not assessed
Table 2a: Use of MenB-FHbp (Trumenba®) in adolescents and young adults (including college 

students): Evidence Table

Outcome Design 

(#studies)

Initial 

Evidence

Risk of Bias Inconsistency Indirectness Imprecision Publication 

Bias

Others Final

Evidence 

Type

Overall 

Evidence 

Type

Benefits

Short-term 

Immunogenicity

2 RCTs 1 Not serious Serious**

(-1)

Serious ***

(-1)

Not serious Unable to 

assess

Yes##

(+1)

2 2

1 Obs 3 Not serious Not 

applicable

Serious ***

(-1)

Not serious Unable to 

assess

None 4

Persistence in 

Immunogenicity

48 months post 

vaccination

1 Obs 3 Serious* 

(-1)

Not 

applicable

Serious ***

(-1)

Minor *# Unable to 

assess

None 4 4

MenB 

immunogenicity 

with 

concomitant 

vaccination 

(Non-inferiority) 

+

2 RCTs 1 Not serious Not serious Serious ***

(-1)

Not serious Unable to 

assess 

None 2 2

Harms

Serious Adverse 

Events (SAEs)

5 RCTs 1 Not serious Not serious Not serious Serious #

(-1)

Unable to 

assess

None 2 2

Safety with 

Concomitant 

vaccination 

(SAEs)

2 RCTs 1 Not serious Not serious Not serious Serious #

(-1)

Unable to 

assess

None 2 2

Footnotes: 

+ Concomitant administration with Tdap/IPV or 4vHPV

* Very small sample size

**Significant heterogeneity; I-square ranges between 43-81% — Downgraded 1

*** Studies assessed correlate of protection and not directly efficacy – downgraded by 1

*# The CI around the effect estimate includes both effect and non-effect in two strains not common in the U.S.

# The CI around the effect estimate includes both effect and non-effect – downgraded by 1

## Very strong strength of association: relative risk ranges between 4.64 between 12.26 – upgraded by 1

Table 2b: Considerations for Vaccine Use: MenB-FHbp (Trumenba®)

Key Factors Comments

Balance between 

benefits and harms

Among healthy adolescents and young adults (including college students), the 

vaccine is immunogenic in the short-term and persists up to 4 years after 

vaccination. MenB-FHbp is safe for concomitant vaccination with 4vHPV, 

MenACWY, Tdap and Tdap/IPV. Low disease burden lowers overall benefits.

Evidence type for benefits and harms

MenB-FHbp vaccine 

use among healthy 

adolescent and 

young adults 

(including college 

students) 

Benefits:

Short term immunogenicity: Evidence Type 2

Persistence in Immunogenicity (48 months): Evidence Type 4

MenB immunogenicity with concomitant vaccination: Evidence Type 2

Harms:

Serious Adverse Events: Evidence Type 2

SAEs following concomitant vaccination: Evidence Type 2
Summary: 

After reviewing the available data, including the result of the GRADE analysis, the Advisory Committee on 

Immunization Practices (ACIP) recommended that adolescents and young adults aged 16 through 23 years 

may be vaccinated with a MenB vaccine to provide short term protection against most strains of 

serogroup B meningococcal disease. The preferred age for MenB vaccination is 16 through 18 years of 

age (recommendation Category B). Category B recommendations are made for individual clinical 

decision making. The full recommendations for the use of MenB vaccines in adolescents and young 

adults (including college students) are available on the ACIP website [ADD LINK TO RECOMMENDATION].

References

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