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GRADE: Inclusion of MenACWY-TT (MenQuadfi) as an option for meningococcal serogroup A, C, W, and Y (MenACWY) vaccination according to currently recommended dosing and schedulesGrading of Recommendations, Assessment, Development, and Evaluation						Print
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			IntroductionMethods for GRADESummary
		
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Introduction
Meningococcal disease is an uncommon but severe bacterial infection that can progress rapidly. One in ten persons with meningococcal disease die despite proper antibiotic treatment, and one in five survivors have long-term sequelae.
Despite the current low incidence of meningococcal disease in the United States, certain groups are at increased risk for meningococcal disease. Serogroup A, C, W, Y (MenACWY) meningococcal vaccines are currently recommended for use in adolescents aged 11 – 18 years, persons with certain underlying conditions (persistent complement component deficiency, complement inhibitor (e.g., eculizumab [Soliris®]) use, anatomic or functional asplenia, and HIV), microbiologists with routine exposure to *Neisseria meningitidis* isolates, persons at increased risk due to a meningococcal disease outbreak caused by serogroup A, C, W, or Y, persons who travel to or reside in countries where meningococcal disease is endemic or hyperendemic, unvaccinated or under-vaccinated college freshmen living in residence halls, and military recruits. (1,2)
MenACWY-TT (MenQuadfi, Sanofi-Pasteur) is a MenACWY conjugate vaccine that was approved in the United States in April 2020 for use in individuals aged 2 years or older. Considering availability of the newly licensed MenACWY-TT vaccine, the ACIP Meningococcal Vaccines Work Group assessed data related to potential benefits and harms of including MenACWY-TT as an option for meningococcal ACWY vaccination, including through the Vaccines for Children (VFC) program, according to currently recommended dosing and schedules.
A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was completed for the MenACWY-TT vaccine to assess the certainty of evidence for outcomes associated with this vaccine. Additional factors related to potential use of the MenACWY-TT vaccine were assessed as part of the Evidence to Recommendations Framework (EtR).
**Top of Page
Methods for GRADE
A systematic review and GRADE of the evidence for MenACWY-TT vaccine was conducted and presented to ACIP in June 2020.  No conflicts of interest were reported by CDC staff or the ACIP Meningococcal Vaccines Work Group members involved in the GRADE analysis. As a basis for the GRADE analysis, the policy question consisting of the population, intervention, comparison, and outcomes of interest was defined (Table 1).
Table 1: Policy question and definition of the Population, Intervention, Comparison, and Outcome for GRADE analysis.
Table 1
Policy question: Should MenACWY-TT (MenQuadfi) be included as an option for meningococcal ACWY vaccination according to currently recommended dosing and schedules?Population
Persons aged ≥ 2 years currently recommended to receive meningococcal conjugate (ACWY) vaccinesIntervention
Vaccination with MenACWY-TT according to currently recommended dosing and schedulesComparison
Vaccination with MenACWY-D and MenACWY-CRM according to currently recommended dosing and schedulesOutcomes
Serogroup A, C, W, or Y meningococcal disease
**Short-term immune response**
**Persistence of immune response**
**Immune interference due to co-administration with other routine adolescent vaccines**
**Serious adverse events**
Bold font indicates outcomes with evidence included in the GRADE analysis
A search was conducted for studies in any language from PubMed, Medline, Embase, CINAHL, Cochrane, Scopus, clinicaltrials.gov, and clinicaltrialsregister.eu databases using search string: MenACYW-TT, MenACYWTT, MenACYW TT, MCV4-TT, MCV4TT, MCV4 TT, MenQuadfi, and “vaccin*” and “(immunogenicity or efficacy or effectiveness or impact or safety or adverse event*)”. Efforts were made to obtain unpublished or other relevant data from the manufacturer.
Studies were included that presented primary data on MenACWY-TT (MenQuadfi).
One hundred forty-nine references were identified. After screening titles and abstracts, 10 studies were included in the GRADE analysis. Characteristics of these studies are presented in Table 2.
Of note, the data reviewed and included in GRADE do not include evidence related to those individuals recommended to receive meningococcal vaccines based on underlying medical conditions, as these groups were excluded from the evaluated studies. The GRADE tables reflect this consideration.
Beneficial and harmful outcomes for the GRADE assessment were selected by the Work Group during Work Group calls. The Work Group deemed serogroup A, C, W, and Y meningococcal disease, short-term immunogenicity, coadministration with routine adolescent vaccines, and serious adverse events (SAEs) to be critical outcomes (Table 1). Persistence of the immune response was deemed an important outcome. Short-term immunogenicity, persistence of the immune response, coadministration with routine adolescent vaccines, and SAEs were included in the evidence profiles; no data were available on prevention of serogroup A, C, W, and Y meningococcal disease.
Because of the absence of data on use of MenACWY-TT among individuals with underlying medical conditions, two GRADE analyses were conducted for each of the four included outcomes: one for healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions, and one for individuals at increased meningococcal disease risk because of underlying medical conditions. This resulted in a total of 8 GRADE tables.
Table 2. Study References
Table 2
Study Code
Study Reference
ClinicalTrials.gov IdentifierMET54
Vesikari T et al. (2020) “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Toddlers.” Human Vaccines & Immunotherapeutics. https://doi.org/10.1080/21645515.2020.1733869, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004367-20/results
NCT03205358MET51
Vesikari T et al. (2019) “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers 12 to 23 Months of Age.” 37th Annual Meeting of the European Society of Pediatric Infectious Diseases (ESPID). https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000749-30/results
NCT02955797MET35
Simon M et al. (2019) “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered in Healthy Children 2 to 9 Years of Age.” ID Week 2019. https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-001471-20/results
NCT03077438MET56
Áñez G et al. (2020) “Immunogenicity and Safety of a Booster Dose of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adolescents and Adults.” Human Vaccines & Immunotherapeutics. https://doi.org/10.1080/21645515.2020.1733867, https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-001470-18/results
NCT02752906MET43
Peterson J et al. (2019) “Immune Lot Consistency, Immunogenicity, and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adolescents and Adults Aged 10 to 55 Years.” ID Week 2019. https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-001468-48/results
NCT02842853MET44
Kirstein J et al. (2020) “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adults 56 Years and Older.” Human Vaccines & Immunotherapeutics. https://doi.org/10.1080/21645515.2020.1733868
NCT01732627MET49
Esteves-Jaramillo et al. (2020) “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adults Age 56 Years and Older.” Vaccine. https://doi.org/10.1016/j.vaccine.2020.04.067
NCT02842866MET50
Chang L et al. (2020) “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Adolescents.” Vaccine. https://doi.org/10.1016/j.vaccine.2020.03.017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001963-35/results
NCT02199691MET57
“Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Other Pediatric Vaccines in Healthy Toddlers.” https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-001472-38/results
NCT03205371MET62
“Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered as a Booster Dose in Children Vaccinated 3 Years Earlier as Toddlers.” https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001993-40/results
NCT03476135Table 3: Characteristics of the included studies for MenACWY-TT (MenQuadfi)
Table 3
Study Code
Study design
Population
Country
N
(MenACWY-TT)
N
(comparison)
OutcomeMET54
Phase II
randomized, open-label
12-24 months
Finland
94
94
Immunogenicity, safetyMET51
Phase III
randomized, modified double blind
12-23 months
Spain, Finland, Germany, Hungary
506
404
Immunogenicity, safetyMET35
Phase III
randomized, modified double-blind
2-9 years
United States, Puerto Rico
480
482
Immunogenicity, safetyMET43
Phase III
randomized, modified double-blind
10-17 years,
18-55 years
United States
1098, 1410**
300, 293**
Immunogenicity, safetyMET44
Phase II
randomized, open label
56+ years
United States
201
100
Immunogenicity, safetyMET49
Phase III
randomized, modified double-blind
56+ years
United States, Puerto Rico
448
453
Immunogenicity, safetyMET56*
Phase III
randomized, modified double-blind
15+ years
United States, Puerto Rico
403
407
Immunogenicity, safetyMET50
Phase II
randomized, open-label
10-17 years
United States
499, 391^
500, 296^
Immunogenicity, safety, coadministration with other vaccinesMET57
Phase III
randomized, open-label
12-23 months
Mexico, Russia, South Korea, Thailand
294, 589^
294
Safety, coadministration with other vaccinesMET62*
Phase III
open-label; follow-up to MET54
4-5 years
Finland
42
49
Safety, persistence of antibody response
Table 3 Footnotes
*Safety and/or immunogenicity evaluated after booster dose
**N’s for 10-17y and 18-55y age groups, respectively
^N’s in meningococcal vaccine only and co-administration groups, respectively
**Top of Page
Short-term immunogenicity (Tables 4-15)
Table 4. Summary data on short-term immunogenicity of MenACWY-TT (MenQuadfi)
Table 4
Study Code
Participant age
N (MenACWY-TT)
N (comparison)
Comparator Vaccine
GMT**ratios***
Absolute difference in % seroresponders^^
InterpretationMET54
12-24 months
94
94
MCV4-TT**
1.25-17.36
0.1-14.0
Descriptive; higher GMTs and % seroresponders with MenACWY-TTMET51
12-23 months
491
395
MCV4-TT**
0.82-7.59
-0.6-19.7
Non-inferiorMET35
2-9 years
458
460
MenACWY-CRM
1.09-14
7.6-47.4
Non-inferiorMET50
10-17 years
499
500
MenACWY-CRM
1.25-7.53
9.2-24.6
Non-inferiorMET43
10-17 years
1098
300
MenACWY-D
1.64-11.4
9.9-42.3
Non-inferiorMET43
18-55 years
1410
293
MenACWY-D
2.03-6.24
19.6-41.1
Non-inferiorMET44
56+ years
201
100
MPSV4
1.60-2.61
11.2-26.5
Descriptive; higher GMTs and % seroresponders with MenACWY-TTMET49
56+ years
448
453
MPSV4
1.75-4.07
15.7-31
Non-inferiorMET56^
15+ years
384
389
MenACWY-D
1.68-4.37
1.8-7.4
Non-inferiorTable 4 Footnotes
*Ratio calculated as [GMT (MenACWY-TT)] / [GMT (comparator vaccine)]. Range of GMT ratios for serogroups A, C, W, Y is shown
**Nimenrix, not licensed in US
^Study assessed use of MenACWY-TT vs. MenACWY-D for booster dose
^^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8. Absolute difference calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (comparator vaccine)]; positive results favor MenACWY-TT. Range of absolute differences for serogroups A, C, W, Y is shown
Table 5. Short-term immunogenicity data from Study MET54, conducted in persons aged 12-24 months
Table 5
Serogroup
GMT MenACWY-TT
GMT
MCV4-TT*
GMTR**
% seroresponders^ with MenACWY-TT
% seroresponders^ with comparator vaccine
Absolute difference in % seroresponders^^A
76.8
61.5
1.25
96.7
91.9
4.8C
492.9
28.4
17.36
100
86.0
14W
71.7
44.5
1.61
98.9
96.5
2.4Y
96.6
76.4
1.26
98.9
98.8
0.1
Table 5 Footnotes
*Nimenrix, not licensed in the US
**Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
^^Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
Table 6. Short-term immunogenicity data from Study MET51, conducted in persons aged 12-23 months
Table 6
Serogroup
GMT MenACWY-TT
**GMT
MCV4-TT***
GMTR**
% seroresponders^ with MenACWY-TT
% seroresponders^ with comparator vaccine
Absolute difference in % seroresponders^^A
29.9
34.5
0.819
76.5
77.1
-0.6C
880
77.1
7.59
97.1
77.4
19.7W
24.4
17.7
1.32
70.8
68.4
2.4Y
41.7
31.9
1.28
84.8
78.9
5.9
Table 6 Footnotes
*Nimenrix, not licensed in the US
**Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
^^Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
Table 7. Short-term immunogenicity data from Study MET35, conducted in persons aged 2-9 years
Table 7
Serogroup
GMT MenACWY-TT
GMT MenACWY-CRM
GMTR*
% seroresponders^ with MenACWY-TT
% seroresponders^ with comparator vaccine
Absolute difference in % seroresponders**A
24.8
22.6
1.09
55.4
47.8
7.6C
238
17
14.0
95.2
47.8
47.4W
37.5
26.2
1.43
78.8
64.1
14.7Y
68.8
43.5
1.58
91.5
79.3
12.2
Table 7 Footnotes
*Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
**Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
Table 8. Short-term immunogenicity data from Study MET50, conducted in persons aged 10-17 years
Table 8
Serogroup
Geometic Mean Titers (GMT) MenACWY-TT
GMT MenACWY-CRM
GMT Ratios
(GMTR)*
% seroresponders^ MenACWY-TT
% seroresponders^ MenACWY-CRM
Absolute difference in % seroresponders**A
44.1
35.2
1.25
75.6
66.4
9.2C
387.0
51.4
7.53
97.2
72.6
24.6W
86.9
36.0
2.41
86.2
66.6
19.6Y
75.7
27.6
2.74
97.0
80.8
16.2
Table 8 Footnotes
*Calculated as [GMT (MenACWY-TT)] / [GMT (MenACWY-CRM)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
**Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (MenACWY-CRM)]
Table 9. Short-term immunogenicity data from Study MET43, conducted in persons aged 10-17
Table 9
Serogroup
GMT MenACWY-TT
GMT
Men-ACWY-D
GMTR*
% seroresponders^ with MenACWY-TT
% seroresponders^ with comparator vaccine
Absolute difference in % seroresponders**A
78
44.2
1.76
74
55.3
18.7C
504
44.1
11.4
95.6
53.3
42.3W
97.2
59.2
1.64
84.5
72
12.5Y
208
80.3
2.59
95.6
85.7
9.9
Table 9 Footnotes
*Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
**Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
Table 10. Short-term immunogenicity data from Study MET43, conducted in persons aged 18-55
Table 10
**Serogroup**
**GMT MenACWY-TT**
**GMT
Men-ACWY-D**
**GMTR***
**% seroresponders^ with MenACWY-TT**
**% seroresponders^ with comparator vaccine**
**Absolute difference in % seroresponders****A
106
52.3
2.03
73.5
53.9
19.6C
234
37.5
6.24
83.4
42.3
41.1W
75.6
33.2
2.27
77
50.2
26.8Y
219
54.6
4.00
88.1
60.8
27.3
Table 10 Footnotes
*Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
**Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
Table 11. Short-term immunogenicity data from Study MET44, conducted in persons aged 56+
Table 11
Serogroup
GMT MenACWY-TT
GMT
MPSV4
GMTR*
% seroresponders^ with MenACWY-TT
% seroresponders^ with comparator vaccine
Absolute difference in % seroresponders**A
51.0
31.8
1.60
65.1
46.8
18.3C
48.3
18.5
2.61
70.8
59.6
11.2W
29.0
17.1
1.70
74.4
55.3
19.1Y
41.9
16.6
2.52
75.4
48.9
26.5
Table 11 Footnotes
*Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
**Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
Table 12. Short-term immunogenicity data from Study MET49, conducted in persons aged 56+
Table 12
Serogroup
GMT MenACWY-TT
GMT
MPSV4
GMTR*
% seroresponders^ with MenACWY-TT
% seroresponders^ with comparator vaccine
Absolute difference in % seroresponders**A
55
31
1.75
58.2
42.5
15.7C
101
25
4.07
77.1
49.7
27.5W
28
15
1.82
62.6
44.8
17.8Y
69
21
3.30
74.4
43.4
31.0
Table 12 Footnotes
*Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
**Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
Table 13. Short-term immunogenicity data from Study MET56^, conducted in persons aged 15+
Table 13
Serogroup
GMT MenACWY-TT
GMT
Men-ACWY-D
GMTR*
% seroresponders with MenACWY-TT^^
% seroresponders with comparator vaccine^^
Absolute difference in % seroresponders**A
497
296
1.68
92.2
87.1
5.0C
2618
599
4.37
97.1
91.8
5.4W
1747
723
2.42
98.2
90.7
7.4Y
2070
811
2.55
97.4
95.6
1.8
Table 13 Footnotes
^Study assessed immunogenicity after booster dose of indicated vaccines
*Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
**Calculated as [% seroresponders (MenACWY-TT)] – [% seroresponders (Comparator)]
^^Seroresponse: post-vaccination titer of ≥1:16 for subjects with pre-vaccination titer <1:8; 4-fold increase in titer post-vaccination for subjects with pre-vaccination titer ≥1:8.
Table 14. GRADE table short-term immunogenicity of MenACWY-TT vaccination in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions:
Table 14
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison8
Randomized trials
No serious*
No serious
No serious
No serious
None
5083
2984
Noninferior
See study specific slides
1
CRITICALTable 14 Footnotes
* Although most trials were not fully double-blinded, outcomes were objective titers and laboratory staff testing the samples were blinded to group assignment of the participants.
Table 15. GRADE table: short-term immunogenicity of MenACWY-TT vaccination in individuals at increased meningococcal disease risk because of underlying medical conditions:
Table 15
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison8
Randomized trials
No serious*
No serious
Very serious^
No serious
None
5083
2984
Noninferior
See study specific tables
3
CRITICALTable 15 Footnotes
* Although most trials were not fully double-blinded, outcomes were objective titers and laboratory staff testing the samples were blinded to group assignment of the participants.
^Studies did not include individuals at increased meningococcal disease risk due to underlying medical conditions (complement component deficiency, anatomic or functional asplenia, or HIV)
**Top of Page
Serious adverse events (Tables 16-18)
Table 16. Data on serious adverse events following vaccination with MenACWY-TT (MenQuadfi)
Table 16
Study Code
Participant age
% SAE
MenACWY-TT
% SAE
Comparator group
Absolute % difference
N related to vaccineMET54
12-24 months
1.1
0
1.1
0MET51
12-23 months
0.8
0.7
0.1
0MET57
12-23 months
0.0 – 7.7
0.0 – 3.8*
-1.0 – 4.0
0MET35
2-9 years
1.4
0.6
0.8
0MET50
10-17 years
0.8
0.8
0
0MET43
10-17 years
0.3
0.9
-0.6
0MET43
18-55 years
1.6
0.6
1.0
0MET44
56+ years
0.0
0.0
0.0
0MET49
56+ years
3.3
3.3
0
0MET62**
4-5 years
0.0
NA^
NA^
0MET56**
15+ years
1.2
1.0
0.2
0Table 16 Footnotes
*Comparator group includes other infant/toddler vaccines but no meningococcal vaccine
**Safety and/or immunogenicity evaluated after booster dose
^Randomized trial for persistence after primary dose; no comparison group for safety data after booster
Table 17. GRADE table: Safety of MenACWY-TT in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions
Table 17
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison9
Randomized trials
Serious*
No serious
No serious
No serious
None
6413
3623
No vaccine related SAEs
2
CRITICALTable 17 Footnotes
*Most trials not fully double-blinded and outcome measure criteria are not described (whether SAE is related to vaccine)
Table 18. GRADE tables: Safety of MenACWY-TT in individuals at increased meningococcal disease risk because of underlying medical conditions
Table 18
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison9
Randomized trials
Serious*
No serious
Very serious^
No serious
None
6413
3623
No vaccine related SAEs
4
CRITICALTable 18 Footnotes
*Most trials not fully double-blinded and outcome measure criteria are not described (whether SAE is related to vaccine)
^Studies did not include individuals at increased meningococcal disease risk due to underlying medical conditions (complement component deficiency, anatomic or functional asplenia, or HIV)
**Top of Page
Persistence of immune response (Tables 19-21)
Table 19. Data on persistence of the immune response to of MenACWY-TT (MenQuadfi) in 4-5 year olds vaccinated three years previously with MenACWY-TT or MCV4-TT
Table 19
Study Code
Participant age
N
(MenACWY-TT)
N
(MCV4-TT*)
Serogroup
GMT MenACWY-TT
GMT
MCV4-TT
GMT Ratios (GMTR)**MET62
4-5 years
40
44
A
12.1
16.5
0.73C
106
11.7
9.1W
48.5
21.9
2.2Y
30.9
17.6
1.8Table 19 Footnotes
*Nimenrix, not licensed in the United States
**Calculated as [GMT (MenACWY-TT)] / [GMT (Comparator)]
Table 20. GRADE table: Persistence of MenACWY-TT in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions
Table 20
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison1
Randomized trial
Serious*
NA
Serious^
Serious**
None
40
44
Higher GMTs for serogroups C, W, Y; lower for serogroup A
4
IMPORTANTTable 20 Footnotes
*Fewer than 50% of participants who received primary dose were evaluated for immune persistence
^Study conducted in Russia in children vaccinated as toddlers, an age group for which MenACWY-TT is not currently licensed in the United States.
**Small number of participants in each arm
Table 21. GRADE table: Persistence of MenACWY-TT in individuals at increased meningococcal disease risk because of underlying medical conditions
Table 21
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison1
Randomized trial
Serious*
NA
Very serious^
Serious**
None
40
44
Higher GMTs for serogroups C, W, Y; lower for serogroup A
4
IMPORTANTTable 21 Footnotes
*Fewer than 50% of participants who received primary dose were evaluated for immune persistence
^Study conducted in Russia in children vaccinated as toddlers, an age group for which MenACWY-TT is not currently licensed in the United States; study did not include individuals at increased meningococcal disease risk due to underlying medical conditions (complement component deficiency, anatomic or functional asplenia, HIV)
**Small number of participants in each arm
**Top of Page
Immune interference due to coadministration with routine adolescent vaccines (Tables 22-25)
Table 22. Data on immune interference due to coadministration with routine adolescent vaccines (Study MET50): Response to quadrivalent HPV vaccine
Table 19
HPV Type
GMT MenACWY-TT+Tdap+HPV
GMT Tdap+HPV
GMTR*
Interpretation6
800
800
1.00
Non-inferior11
1492
1402
1.06
Non-inferior16
6002
6395
0.939
Non-inferior18
1271
1118
1.14
Non-inferiorTable 22 Footnotes
*Calculated as [GMT (MenACWY-TT+Tdap+HPV)] / [GMT (Tdap+HPV)]
Table 23. Data on immune interference due to coadministration with routine adolescent vaccines (Study MET50): Response to quadrivalent Tdap vaccine
Table 23
Antigen
% with ≥ 1.0 IU/mL ab MenACYW-TT+Tdap+HPV
% with ≥ 1.0 IU/mL ab Tdap+HPV
Absolute % difference
InterpretationTetanus
99.7
99.6
0.1
Non-inferiorDiphtheria
97.8
98.9
-1.1
Non-inferiorPertussis antigen
GMC
MenACYW-TT+Tdap+HPV
GMC
Tdap+HPV
GMC Ratio
InterpretationPT
37.5
44.4
0.845
Non-inferiorFHA
180
242
0.746
Did not meet non-inferiority criteriaPRN
200
265
0.753
Did not meet non-inferiority criteriaFIM
339
499
0.679
Did not meet non-inferiority criteriaTable 24. GRADE table: Coadministration of routine adolescent vaccines with MenACWY-TT in healthy adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions
Table 24
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison1
Randomized trial
Serious*
NA
No serious
No serious
None
Tdap: 360
HPV: 242
Tdap: 263
HPV: 164
Noninferior for Tetanus, Diphtheria, HPV, Pertussis toxoid antigen
Noninferiority not met for Pertussis FHA, PRN, FIM antigens**
2
CRITICALTable 24 Footnotes
*Unexplained reduction in number of participants evaluated for HPV immunogenicity
**The clinical relevance of the diminished responses to the pertussis antigens is unknown. Similar coadministration issues have been observed with other meningococcal vaccines.
Table 25. GRADE tables: Coadministration of routine adolescent vaccines with MenACWY-TT in individuals at increased meningococcal disease risk because of underlying medical conditions
Table 24
Certainty assessment
No of patients
Results
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations
Intervention
Comparison1
Randomized trial
Serious*
NA
Very serious
No serious
None
Tdap: 360
HPV: 242
Tdap: 263
HPV: 164
Noninferior for Tetanus, Diphtheria, HPV, Pertussis toxoid antigen
Noninferiority not met for Pertussis FHA, PRN, FIM antigens**
4
CRITICALTable 25 Footnotes
*Unexplained reduction in number of participants evaluated for HPV immunogenicity
** The clinical relevance of the diminished responses to the pertussis antigens is unknown. Similar coadministration issues have been observed with other meningococcal vaccines.
^Studies did not include individuals at increased meningococcal disease risk due to underlying medical conditions (complement component deficiency, anatomic or functional asplenia, or HIV)
Summary
To summarize the GRADE assessment for use of MenACWY-TT, for healthy individuals the certainty of evidence was rated as 1 for short term immunogenicity, 4 for persistence of the immune response, and 2 for coadministration of routine adolescent vaccines and serious adverse events; however, for people with underlying medical conditions increasing their risk of meningococcal disease, quality of evidence is a 3 for short term immunogenicity and 4 for the other outcomes.
Table 26. GRADE Summary of Evidence table for use of MenACWY-TT in healthy individuals (including adolescents and individuals at increased meningococcal disease risk for reasons other than underlying medical conditions) and individuals at increased meningococcal disease risk due to underlying medical conditions.
Table 26
Type
Outcome
Importance
Included in evidence profile
Certainty for healthy individuals
Certainty for individuals with medical conditions that increase meningococcal disease riskBenefits
Serogroup A, C, W, or Y meningococcal disease
Critical
No
N/A
N/A**Short-term immune response**
**Critical**
**Yes**
**1**
**3****Persistence of immune response**
**Important**
**Yes**
**4**
**4**Harms
**Immune interference due to co-administration with other routine adolescent vaccines**
**Critical**
**Yes**
**2**
**4****Serious adverse events**
**Critical**
**Yes**
**2**
**4**ACIP reviewed the results of both the GRADE analysis and the Evidence to Recommendations framework in June 2020 and voted to include MenACWY-TT (MenQuadfi) as an option for meningococcal serogroup A, C, W, and Y (MenACWY) vaccination for children aged ≥2 years in the Vaccines for Children (VFC) program according to currently recommended dosing and schedules.**Top of Page
References
Prevention and Control of Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Recommendations and Reports March 22, 2013 / 62(RR02);1-22. www.cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.htm
MacNeil JR, Rubin LG, Patton M, Ortega-Sanchez IR, Martin SW. Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons — Advisory Committee on Immunization Practices, 2016. MMWR Morb Mortal Wkly Rep 2016;65:1189–1194. DOI: https://dx.doi.org/10.15585/mmwr.mm6543a3**Top of Page
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							Last Reviewed:  September 24, 2020						Source: 	National Center for Immunization and Respiratory Diseases
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