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 schedules

Grading of Recommendations, Assessment, Development, and Evaluation

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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).

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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) vaccines
Intervention Vaccination with MenACWY-TT according to currently recommended dosing and schedules
Comparison Vaccination with MenACWY-D and MenACWY-CRM according to currently recommended dosing and schedules
Outcomes
  • 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 Identifier
MET54 Vesikari T et al. (2020) “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Toddlers.” Human Vaccines & Immunotherapeutics. https://doi.org/10.1080/21645515.2020.1733869external icon, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004367-20/resultsexternal icon NCT03205358
MET51 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/resultsexternal icon NCT02955797
MET35 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/resultsexternal icon NCT03077438
MET56 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/10.1080/21645515.2020.1733867external icon, https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-001470-18/resultsexternal icon NCT02752906
MET43 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/resultsexternal icon NCT02842853
MET44 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/10.1080/21645515.2020.1733868external icon NCT01732627
MET49 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.2020.04.067external icon NCT02842866
MET50 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.2020.03.017external icon, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001963-35/resultsexternal icon NCT02199691
MET57 “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/resultsexternal icon NCT03205371
MET62 “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/resultsexternal icon NCT03476135

Table 3: Characteristics of the included studies for MenACWY-TT (MenQuadfi)

Table 3
Study Code Study design Population Country N
(MenACWY-TT)
N
(comparison)
Outcome

MET54

Phase II
randomized, open-label

12-24 months

Finland

94

94

Immunogenicity, safety

MET51

Phase III
randomized, modified double blind

12-23 months

Spain, Finland, Germany, Hungary

506

404

Immunogenicity, safety

MET35

Phase III
randomized, modified double-blind

2-9 years

United States, Puerto Rico

480

482

Immunogenicity, safety

MET43

Phase III
randomized, modified double-blind

10-17 years,
18-55 years

United States

1098, 1410**

300, 293**

Immunogenicity, safety

MET44

Phase II
randomized, open label

56+ years

United States

201

100

Immunogenicity, safety

MET49

Phase III
randomized, modified double-blind

56+ years

United States, Puerto Rico

448

453

Immunogenicity, safety

MET56*

Phase III
randomized, modified double-blind

15+ years

United States, Puerto Rico

403

407

Immunogenicity, safety

MET50

Phase II
randomized, open-label

10-17 years

United States

499, 391^

500, 296^

Immunogenicity, safety, coadministration with other vaccines

MET57

Phase III
randomized, open-label

12-23 months

Mexico, Russia, South Korea, Thailand

294, 589^

294

Safety, coadministration with other vaccines

MET62*

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

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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^^ Interpretation

MET54

12-24 months

94

94

MCV4-TT**

1.25-17.36

0.1-14.0

Descriptive; higher GMTs and % seroresponders with MenACWY-TT

MET51

12-23 months

491

395

MCV4-TT**

0.82-7.59

-0.6-19.7

Non-inferior

MET35

2-9 years

458

460

MenACWY-CRM

1.09-14

7.6-47.4

Non-inferior

MET50

10-17 years

499

500

MenACWY-CRM

1.25-7.53

9.2-24.6

Non-inferior

MET43

10-17 years

1098

300

MenACWY-D

1.64-11.4

9.9-42.3

Non-inferior

MET43

18-55 years

1410

293

MenACWY-D

2.03-6.24

19.6-41.1

Non-inferior

MET44

56+ years

201

100

MPSV4

1.60-2.61

11.2-26.5

Descriptive; higher GMTs and % seroresponders with MenACWY-TT

MET49

56+ years

448

453

MPSV4

1.75-4.07

15.7-31

Non-inferior

MET56^

15+ years

384

389

MenACWY-D

1.68-4.37

1.8-7.4

Non-inferior

Table 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

4.8

C

492.9

28.4

17.36

100

86.0

14

W

71.7

44.5

1.61

98.9

96.5

2.4

Y

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

-0.6

C

880

77.1

7.59

97.1

77.4

19.7

W

24.4

17.7

1.32

70.8

68.4

2.4

Y

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

7.6

C

238

17

14.0

95.2

47.8

47.4

W

37.5

26.2

1.43

78.8

64.1

14.7

Y

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

9.2

C

387.0

51.4

7.53

97.2

72.6

24.6

W

86.9

36.0

2.41

86.2

66.6

19.6

Y

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

18.7

C

504

44.1

11.4

95.6

53.3

42.3

W

97.2

59.2

1.64

84.5

72

12.5

Y

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

19.6

C

234

37.5

6.24

83.4

42.3

41.1

W

75.6

33.2

2.27

77

50.2

26.8

Y

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

18.3

C

48.3

18.5

2.61

70.8

59.6

11.2

W

29.0

17.1

1.70

74.4

55.3

19.1

Y

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

15.7

C

101

25

4.07

77.1

49.7

27.5

W

28

15

1.82

62.6

44.8

17.8

Y

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

5.0

C

2618

599

4.37

97.1

91.8

5.4

W

1747

723

2.42

98.2

90.7

7.4

Y

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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
8 Randomized trials No serious* No serious No serious No serious None 5083 2984 Noninferior
See study specific slides
1 CRITICAL

Table 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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
8 Randomized trials No serious* No serious Very serious^ No serious None 5083 2984 Noninferior
See study specific tables
3 CRITICAL

Table 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)

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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 vaccine

MET54

12-24 months

1.1

0

1.1

0

MET51

12-23 months

0.8

0.7

0.1

0

MET57

12-23 months

0.0 – 7.7

0.0 – 3.8*

-1.0 – 4.0

0

MET35

2-9 years

1.4

0.6

0.8

0

MET50

10-17 years

0.8

0.8

0

0

MET43

10-17 years

0.3

0.9

-0.6

0

MET43

18-55 years

1.6

0.6

1.0

0

MET44

56+ years

0.0

0.0

0.0

0

MET49

56+ years

3.3

3.3

0

0

MET62**

4-5 years

0.0

NA^

NA^

0

MET56**

15+ years

1.2

1.0

0.2

0

Table 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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
9 Randomized trials Serious* No serious No serious No serious None 6413 3623 No vaccine related SAEs 2 CRITICAL

Table 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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
9 Randomized trials Serious* No serious Very serious^ No serious None 6413 3623 No vaccine related SAEs 4 CRITICAL

Table 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)

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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

0.73

C

106

11.7

9.1

W

48.5

21.9

2.2

Y

30.9

17.6

1.8

Table 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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
1 Randomized trial Serious* NA Serious^ Serious** None

40

44

Higher GMTs for serogroups C, W, Y; lower for serogroup A

4 IMPORTANT

Table 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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
1 Randomized trial Serious* NA Very serious^ Serious** None

40

44

Higher GMTs for serogroups C, W, Y; lower for serogroup A

4 IMPORTANT

Table 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

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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* Interpretation

6

800

800

1.00

Non-inferior

11

1492

1402

1.06

Non-inferior

16

6002

6395

0.939

Non-inferior

18

1271

1118

1.14

Non-inferior

Table 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 Interpretation
Tetanus 99.7 99.6 0.1 Non-inferior
Diphtheria 97.8 98.9 -1.1 Non-inferior
Pertussis antigen GMC
MenACYW-TT+Tdap+HPV
GMC
Tdap+HPV
GMC Ratio Interpretation
PT 37.5 44.4 0.845 Non-inferior
FHA 180 242 0.746 Did not meet non-inferiority criteria
PRN 200 265 0.753 Did not meet non-inferiority criteria
FIM 339 499 0.679 Did not meet non-inferiority criteria

Table 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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
1 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 CRITICAL

Table 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 № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison
1 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 CRITICAL

Table 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 risk
Benefits

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

  1. 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. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.htm
  2. 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: http://dx.doi.org/10.15585/mmwr.mm6543a3external icon

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