Meningococcal Disease, Meningococcal Meningitis
Conditions
Keywords
Meningococcal, ACWY-CRM, Conjugate Vaccine, Meningitis, Adolescents, Persistence, Adults
Brief summary
This study is designed to evaluate the immunogenicity and the safety of a quadrivalent vaccine MenACWY-CRM in healthy subjects from 11 to 55 years of age in Korea.
Interventions
BIOLOGICALNovartis MenACWY-CRM
All subjects had blood drawn at Day 1 and Day 29.
BIOLOGICALSaline Placebo
All subjects had blood drawn at Day 1 and Day 29.
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
11 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Individuals eligible for enrollment in this study were those: 1. who were 11-55 years of age inclusive and who, after the nature of the study had been explained: 1. had given written assent and/or for whom the parent/legal representative had provided written informed consent (11-19 years of age). 2. had provided written informed consent (20-55 years of age). 2. who the investigator believed that they or their parents/legal representatives would comply with the requirements of the protocol (e.g., completion of the Diary Card, return for follow-up visit). 3. who were in good health as determined by 1. medical history 2. physical assessment 3. clinical judgment of the investigator 4. who had negative urine pregnancy test for women of childbearing age.
Exclusion criteria
Individuals not eligible to be enrolled in the study were those: 1. who were unwilling or unable to give written informed assent or consent to participate in the study. 2. who were perceived to be unreliable or unavailable for the duration of the study period. 3. who were planning to leave the area of the study site before the end of the study period. 4. who had a previous or suspected disease caused by N. meningitidis. 5. who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment. 6. who had previously been immunized with a meningococcal vaccine. 7. who had received any investigational or non-registered product (drug or vaccine)within 28 days prior to enrollment or who expected to receive an investigational drug or vaccine prior to the completion of the study. 8. who had received any licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who were planning to receive any vaccine within 30 days from the study vaccines. (Exception: Influenza vaccine was administered up to 15 days prior to study vaccination and at least 15 days after study vaccination) 9. who had experienced within the 7 days prior to enrollment significant acute or chronic infection (for example requiring systemic antibiotic treatment or antiviral therapy) or had experienced fever (defined as body temperature ≥38°C) within 3 days prior to enrollment. 10. who had any serious acute, chronic or progressive disease (e.g., any history of neoplasm, cancer, diabetes, cardiac disease, autoimmune disease, HIV infection or AIDS, or blood dyscrasias, with signs of cardiac or renal failure or severe malnutrition). 11. who had epilepsy or any progressive neurological disease. 12. who had a history of any anaphylaxis, serious vaccine reactions, or allergy to any vaccine components, including latex allergies. 13. who had a known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from (for example): 1. received immunosuppressive therapy within 28 days prior to enrollment(any systemic corticosteroid administered for more than 5 days, or in a daily dose \> 1 mg/kg/day prednisone or equivalent during any of 28 days prior to enrollment, or cancer chemotherapy) 2. received immunostimulants 3. received parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 90 days prior to enrollment and for the full length of the study 14. who were known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. 15. who had any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | day 29 | Immunogenicity was measured as the percentage of subjects with hSBA response and associated 95% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y by serum bactericidal assay using human complement, human serum bactericidal assay (hSBA), at day 29 (28 days after MenACWY-CRM vaccination). Seroresponse is defined as: 1. for subjects with a pre-vaccination hSBA titer \< 1:4, a postvaccination hSBA titer ≥ 1:8. 2. for subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the pre-vaccination titer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | day 1 and day 29 | Immunogenicity was assessed as hSBA GMTs and associated 95% CI, measured against N. meningitidis serogroups A, C, W and Y, before the vaccination (baseline, day 1) and at day 29 (28 days after MenACWY-CRM vaccination). |
| Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | day 1 and day 29 | Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI, at baseline before vaccination (day 1) and at day 29 (28 days after MenACWY-CRM vaccination). |
| Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | during 7 days of vaccination | — |
Countries
South Korea
Participant flow
Recruitment details
Participants were enrolled at 8 centres in the Korea.
Pre-assignment details
All enrolled subjects were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| MenACWY-CRM Subjects received one dose of MenACWY-CRM conjugate vaccine. | 297 |
| Placebo Subjects received the saline placebo. | 153 |
| Total | 450 |
Baseline characteristics
| Characteristic | MenACWY-CRM | Placebo | Total |
|---|---|---|---|
| Age Continuous Age, Years | 19.6 years STANDARD_DEVIATION 9.2 | 19.3 years STANDARD_DEVIATION 8.9 | 19.5 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 139 Participants | 77 Participants | 216 Participants |
| Sex: Female, Male Male | 158 Participants | 76 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 117 / 297 | 50 / 153 |
| serious Total, serious adverse events | 0 / 297 | 0 / 153 |
Outcome results
Primary
Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination.
Immunogenicity was measured as the percentage of subjects with hSBA response and associated 95% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y by serum bactericidal assay using human complement, human serum bactericidal assay (hSBA), at day 29 (28 days after MenACWY-CRM vaccination). Seroresponse is defined as: 1. for subjects with a pre-vaccination hSBA titer \< 1:4, a postvaccination hSBA titer ≥ 1:8. 2. for subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the pre-vaccination titer.
Time frame: day 29
Population: Analysis was done on per protocol (PP) population i.e. the subjects who received the vaccine correctly and provided evaluable serum samples at the relevant time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A (N=295,152) | 76 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C (N=293,150) | 86 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W (N=293,151) | 28 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y (N=294,152) | 69 Percentages of subjects |
| Placebo | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y (N=294,152) | 2 Percentages of subjects |
| Placebo | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A (N=295,152) | 1 Percentages of subjects |
| Placebo | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W (N=293,151) | 4 Percentages of subjects |
| Placebo | Percentages of Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C (N=293,150) | 1 Percentages of subjects |
Comparison: The null hypothesis associated with the primary immunogenicity objective is that for at least one of the four serogroups, the percentage of subjects with hSBA seroresponse at 29 days postvaccination is \< 50%.95% CI: [71, 81]Clopper and Pearson
Comparison: The null hypothesis associated with the primary immunogenicity objective is that for at least one of the four serogroups, the percentage of subjects with hSBA seroresponse at 29 days postvaccination is \< 50%.95% CI: [82, 90]Clopper and Pearson
Comparison: The null hypothesis associated with the primary immunogenicity objective is that for at least one of the four serogroups, the percentage of subjects with hSBA seroresponse at 29 days postvaccination is \< 50%.95% CI: [23, 33]Clopper and Pearson
Comparison: The null hypothesis associated with the primary immunogenicity objective is that for at least one of the four serogroups, the percentage of subjects with hSBA seroresponse at 29 days postvaccination is \< 50%.95% CI: [63, 74]Clopper and Pearson
Secondary
Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination.
Immunogenicity was assessed as hSBA GMTs and associated 95% CI, measured against N. meningitidis serogroups A, C, W and Y, before the vaccination (baseline, day 1) and at day 29 (28 days after MenACWY-CRM vaccination).
Time frame: day 1 and day 29
Population: Analysis was done on PP population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 1 (N=295,152) | 2.7 Titers |
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 29 (N=295,152) | 48 Titers |
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 1 (N=293,150) | 7.82 Titers |
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 29 (N=293,150) | 231 Titers |
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 1 (N=293,151) | 51 Titers |
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 29 (N=293,151) | 147 Titers |
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 1 (N=294,152) | 9.01 Titers |
| MenACWY-CRM | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 29 (N=294,152) | 107 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 29 (N=294,152) | 8.4 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 1 (N=295,152) | 2.86 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 1 (N=293,151) | 48 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 29 (N=295,152) | 3 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 1 (N=294,152) | 8.82 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 1 (N=293,150) | 5.94 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 29 (N=293,151) | 47 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 29 (N=293,150) | 6.04 Titers |
Secondary
Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination
Time frame: during 7 days of vaccination
Population: Analysis was done on safety population i.e. the subjects in the exposed population who provided post-baseline safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Injection site induration | 30 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Headache | 39 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Nausea | 22 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Rash | 1 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Injection site erythema | 30 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Fever (≥38°C) | 3 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Myalgia | 45 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Axillary temperature (<38.0°C) | 294 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Chills | 17 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Stayed home | 9 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Arthralgia | 6 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Used analgesic or antipyretic medicines | 7 Subjects |
| MenACWY-CRM | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Injection site pain | 69 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Used analgesic or antipyretic medicines | 3 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Injection site pain | 12 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Injection site erythema | 3 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Injection site induration | 0 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Chills | 7 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Nausea | 10 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Myalgia | 13 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Arthralgia | 4 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Headache | 25 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Rash | 0 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Fever (≥38°C) | 1 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Axillary temperature (<38.0°C) | 152 Subjects |
| Placebo | Number of Subjects Who Reported Local and Systemic Reactogenicity During 7 Days After MenACWY-CRM Vaccination | Stayed home | 2 Subjects |
Secondary
Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination.
Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI, at baseline before vaccination (day 1) and at day 29 (28 days after MenACWY-CRM vaccination).
Time frame: day 1 and day 29
Population: Analysis was done on PP population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 1 (N=295,152) | 13 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 29 (N=295,152) | 79 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 1 (N=293,150) | 49 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 29 (N=293,150) | 99 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 1 (N=293,151) | 89 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 29 (N=293,151) | 98 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 1 (N=294,152) | 54 Percentages of subjects |
| MenACWY-CRM | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 29 (N=294,152) | 94 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 29 (N=294,152) | 51 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 1 (N=295,152) | 15 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 1 (N=293,151) | 87 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup A at Day 29 (N=295,152) | 16 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup Y at Day 1 (N=294,152) | 53 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 1 (N=293,150) | 39 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup W at Day 29 (N=293,151) | 88 Percentages of subjects |
| Placebo | Percentages of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination. | Serogroup C at Day 29 (N=293,150) | 37 Percentages of subjects |