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Immunogenicity and safety of one dose of investigational MenACWY-CRM was assessed in Indian subjects.
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Post-vaccination hSBA ≥8 was 72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively.
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The vaccine was well tolerated with no safety concerns.
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MenACWY-CRM induced a robust immune response in Indian subjects aged 2–75 years.
Summary
Background
This phase 3, multi-center, open-label study evaluated the immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM, Menveo®; Novartis Vaccines and Diagnostics S.r.l., Siena, Italy) in healthy Indian subjects aged 2–75 years, to provide data for licensure in India.
Methods
A total of 180 subjects were enrolled (60 subjects 2–10 years, 60 subjects 11–18 years, and 60 subjects 19–75 years) and received one dose of MenACWY-CRM. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination. Adverse events were collected throughout the 29-day study period.
Results
Percentages of subjects with post-vaccination hSBA ≥8 were 72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively. Geometric mean titers rose 7-fold to 42-fold against the four serogroups. Similar immune responses were observed for the age subgroups 2–10 years, 11–18 years, and 19–75 years. Seroresponse rates at 1 month following vaccination were 72%, 88%, 55%, and 71% for serogroups A, C, W, and Y, respectively. The vaccine was well tolerated with no safety concerns.
Conclusion
A single dose of MenACWY-CRM induced a robust immune response against all four meningococcal serogroups and was well tolerated in an Indian population 2–75 years of age.
Invasive meningococcal disease is one of the most devastating global bacterial infections. There are an estimated 500 000 cases of meningococcal disease every year, causing 50 000 deaths worldwide.
Based on antigenic differences in their capsular polysaccharide, at least 12 serogroups have been identified. The vast majority of invasive meningococcal disease (≥90%) can be attributed to one of six immunologically distinct serogroups: A, B, C, W-135, X, and Y.
The incidence and serogroup distribution varies with age group and geographical location, and changes over time. Serogroups B and C are most prevalent in Europe, Australia, and New Zealand, serogroups A, C, and W-135 are most common in Asia and Africa, serogroups B, C, and Y predominate in the USA, Canada, Latin America, and the Caribbean, and serogroup X has caused sporadic and clustered meningitis cases in Sub-Saharan Africa.
There is limited information available on meningococcal epidemiology in India, however pattern similarities with African epidemics suggest that serogroup A is predominant.
Occasional epidemics of meningococcal disease (mainly serogroup A) in the past century have been reported, most recently in 2005 in Delhi and surrounding districts.
MenACWY-CRM (Menveo®; Novartis Vaccines and Diagnostics S.r.l., Siena, Italy – a GSK company) is a quadrivalent (serogroups A, C, W-135, and Y) meningococcal polysaccharide conjugate vaccine that includes Corynebacterium diphtheria cross-reactive material 197 (CRM197) as the carrier protein. Previous clinical studies have shown that MenACWY-CRM is highly immunogenic against all four meningococcal serogroups and is well tolerated in a wide range of age groups, beginning from 2 months of age.
Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents.
Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.
MenACWY-CRM is currently approved in 64 countries. The vaccine has been approved for use in infants, children, adolescents, and adults, and is also Halal certified, which is relevant to many in the Indian population.
When this study was planned, only unconjugated meningococcal polysaccharide vaccines were available in India. Recently, a quadrivalent meningococcal conjugate vaccine was licensed (Menactra®; Sanofi Pasteur, Swiftwater, PA, USA). The purpose of this study is to support licensure of the GSK MenACWY-CRM vaccine in India. This phase 3, multi-center, open-label study was designed to evaluate the immunogenicity and safety of a single dose of the quadrivalent conjugate vaccine, MenACWY-CRM, in healthy Indian subjects aged 2–75 years.
2. Methods
2.1 Study design and objectives
This phase 3, multi-center, open-label study was conducted at three study centers in India during the period March 2012 to May 2014 (ClinicalTrials.gov identifier NCT01547715; Clinical Trial Registry of India identifier CTRI/2012/02/002452). The study was conducted according to Good Clinical Practice as well as the Ethical Guidelines for Biomedical Research on Human Subjects issued by the Indian Council for Medical Research, India. Ethics review committees approved the study protocol, and written informed consent was obtained from every participant and their parents or legal guardians, where appropriate, prior to enrolment. Enrolment was age-stratified with de-escalation by age, commencing with adults, then adolescents, and then children, with interim safety evaluations of adults and of adolescents.
The immunogenicity objectives of a single dose of MenACWY-CRM was measured by the percentage of subjects with hSBA (serum bactericidal activity using human complement) ≥8, the seroresponse rate at 1 month after vaccination (day 29) (primary objective), and hSBA geometric mean titers (GMTs). Immune responses were assessed as serum bacterial activity using human complement against Neisseria meningitidis serogroups A, C, W, and Y. Safety objectives were to assess the number and percentage of subjects with solicited local and systemic and unsolicited adverse events (AEs) during the 7 days following vaccination. Serious AEs (SAEs), medically attended AEs, and AEs leading to premature study withdrawal were collected throughout the study period, from day 1 to the end of the study.
2.2 Study participants
A total of 180 subjects were enrolled in this study, 60 in each age group: 2–10 years, 11–18 years, and 19–75 years. Eligible study participants were healthy subjects of either sex aged between 2 and 75 years. Female participants of childbearing potential were required to have a negative urine pregnancy test prior to enrolment. Subjects were excluded from the study if they did not provide informed consent, if they had a history of any meningococcal vaccine administration, if they had disease caused by N. meningitidis, or if there had been intimate exposure to an individual with laboratory confirmed N. meningitidis. Additional exclusion criteria were a significant infection within 7 days or fever ≥38 °C within 3 days of enrolment, known reactions to vaccine components, any serious chronic or progressive disease, known or suspected immune disease or impairment, known bleeding diathesis, receipt of blood products, medical history or illness likely to interfere with the results, receipt of any vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment, or previous receipt (within 28 days before study start) or intent to receive any investigational agent or vaccines prior to completion of the study.
2.3 Vaccines
MenACWY-CRM was prepared by extemporaneous mixing of the lyophilized MenA component with the liquid MenCWY component. Each 0.5-ml vaccine dose contained 10 μg of meningococcal serogroup A and 5 μg each of capsular polysaccharide of serogroups C, W-135, and Y conjugated to CRM197. The vaccine was administered as an intramuscular injection into the deltoid muscle of the non-dominant arm.
2.4 Immunogenicity
Blood samples for immunogenicity analyses were obtained on day 1 (pre-vaccination) and day 29 (1 month post-vaccination). Immune responses were assessed as hSBA against meningococcal serogroups A, C, W-135, and Y, according to validated methods, in the laboratories of GSK Vaccines (Marburg, Germany). Pre- and post-vaccination antibody responses were expressed as the percentage of subjects with hSBA ≥8, percentage of subjects with a seroresponse, hSBA GMT, and post-vaccination to pre-vaccination geometric mean ratio (GMR). Seroresponse was defined as a post-vaccination hSBA ≥8 in subjects with a pre-vaccination hSBA <4, and at least 4-fold increase in post-vaccination hSBA in subjects with a pre-vaccination hSBA ≥4.
2.5 Safety
Subjects were observed for a minimum of 30 min post-vaccination to monitor for immediate adverse reactions. Subjects or guardians recorded solicited AEs and any other AEs on diary cards for 7 days after the vaccination. In children 2–5 years of age, injection site tenderness, erythema, and induration, and systemic reactions such as a change in eating habits, sleepiness, irritability, vomiting, diarrhea, and rash were collected. In children 6 years of age and older, injection site pain, erythema, and induration, and systemic reactions including chills, nausea, malaise, myalgia, arthralgia, headache, and rash were collected. Body temperature (fever ≥38 °C) and use of antipyretic medication was also recorded for all subjects. Participants were contacted on day 3 post-vaccination to remind them to complete the diary card.
Serious AEs or AEs resulting in premature withdrawal and other medically attended events were collected from day 1 to day 29. The investigators assessed the AEs for seriousness, severity, and relation to study vaccines. The severity of AEs was categorized as mild, moderate, or severe, if they resulted in no limitation, some limitation, or inability to perform normal daily activities, respectively. Some local AEs such as erythema, induration, and swelling were categorized based on measurements. Assessments of the causal relationship of spontaneous AEs to the study vaccines were classified as not related, possibly related, or probably related by the investigator.
2.6 Statistical analyses
A sample size of 180 subjects aged 2–75 years was considered adequate to examine the primary study objective (seroresponse rate), based on the 95% confidence intervals (CI) of the observed seroresponse. Sixty subjects were planned for enrolment in each age group. Enrolment was based on a 20% drop-out rate, providing approximately 144 evaluable subjects for immunogenicity and approximately 48 subjects in each age group. With 144 subjects, a 95% CI of 42–95% was expected with an observed seroresponse of 50–90%, and with 48 subjects, a 95% CI of 36–99% was expected with an observed seroresponse of 50–90%. Immunogenicity endpoints were evaluated descriptively and no formal statistical hypotheses associated with the immunogenicity objectives of this study were tested.
Percentages of subjects with hSBA ≥8, seroresponse (see earlier definition), hSBA GMTs, GMRs and corresponding 95% Clopper–Pearson CI against serogroups A, C, W, and Y were calculated. GMTs were computed by exponentiating (base 10) least squares means of the logarithmically transformed titers. Titers below the limit of detection would be set to half that limit for the purposes of analysis.
Safety data were evaluated descriptively and expressed as the number or percentage of subjects with AEs in each age group.
Immunogenicity analyses were run on the full analyses set (FAS), which consisted of subjects who provided at least one evaluable serum whose assay result was available for at least one serogroup. Safety was analyzed for all subjects exposed to the study vaccine who provided safety data. All statistical analyses were performed using SAS® version 9.2 (SAS Institute, Cary, NC, USA).
3. Results
A total of 180 subjects were enrolled, 60 subjects within each age subgroup. All enrolled subjects received a single dose of MenACWY-CRM and completed the study with no premature withdrawals. The baseline demographics of the enrolled subjects are presented in Table 1. Gender was mostly equally distributed across age groups, except for a predominance of male participants aged 19–75 years; all subjects were of Asian origin.
Table 1Study population demographics, by age group and overall population
At day 1 before MenACWY-CRM vaccination, the percentage of overall subjects who had baseline hSBA ≥8 was 1%, 21%, and 42% for serogroups A, C, and Y, respectively, whereas the majority of subjects (58%) had a baseline hSBA ≥8 for serogroup W (Figure 1). At day 29 post-vaccination, the percentages of subjects with hSBA ≥8 were 72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively (Figure 1).
Figure 1Percentage of subjects (95% confidence interval) with hSBA ≥8 at baseline (day 1) and 1 month post-vaccination (day 29) against serogroups A, C, W, and Y, by age group and overall population.
In the overall population, the seroresponse rate at 1 month following a single vaccination of MenACWY-CRM was 72%, 88%, 55%, and 71% against serogroups A, C, W, and Y, respectively (Table 2). Among those with a baseline hSBA <4, the seroresponse rate was 72%, 93%, 88%, and 84% for serogroups A, C, W, and Y, respectively. For the subjects with a baseline hSBA ≥4, the seroresponse rate was 100%, 77%, 33%, and 57% for serogroups A, C, W, and Y, respectively. Comparatively few subjects were included for immunogenicity analysis for serogroup A at baseline hSBA ≥4 (n = 4), as compared with serogroups C (n = 53), W (n = 108), and Y (n = 81). There was an overall increase in seroresponse against serogroups W and Y when stratified by baseline hSBA <4.
Table 2Seroresponse rates (95% confidence interval) against serogroups A, C, W, and Y at 1 month post-vaccination (day 29), by age group and overall population
Seroresponse was defined as a post-vaccination hSBA ≥8 for subjects with a pre-vaccination hSBA <4, and an increase in hSBA titer of at least four times the pre-vaccination titer for subjects with a pre-vaccination hSBA ≥4.
2–10 years
11–18 years
19–75 years
Overall
n = 60
n = 59
n = 58
n = 177
Serogroup A
hSBA <1:4
74 (61–85), n = 58
76 (63–86), n = 58
65 (51–770), n = 57
72 (64–78), n = 173
hSBA ≥1:4
100 (16–100), n = 2
100 (3–100), n = 1
100 (3–100), n = 1
100 (40–100), n = 4
Overall
75 (62–85)
76 (63–86)
66 (52–78)
72 (65–79)
Serogroup C
hSBA <1:4
90 (77–97), n = 48
95 (82–99), n = 38
94 (81–99), n = 36
93 (86–97), n = 122
hSBA ≥1:4
60 (26–88), n = 10
81 (58–95), n = 21
82 (60–95), n = 22
77 (64–8), n = 53
Overall
84 (73–93), n = 58
90 (79–96)
90 (79–96)
88 (82–92), n = 175
Serogroup W
hSBA <1:4
88 (69–97), n = 25
90 (70–99), n = 21
86 (65–97), n = 22
88 (78–95), n = 68
hSBA ≥1:4
37 (21–55), n = 35
29 (15–46), n = 38
34 (19–52), n = 35
33 (25–43), n = 108
Overall
58 (45–71)
51 (37–64)
54 (41–68), n = 57
55 (47–62), n = 176
Serogroup Y
hSBA <1:4
76 (61–88), n = 42
89 (71–98), n = 27
92 (73–99), n = 24
84 (75–91), n = 93
hSBA ≥1:4
50 (25–75), n = 16
53 (35–71), n = 32
64 (45–80), n = 33
57 (45–68), n = 81
Overall
69 (55–80), n = 58
69 (56–81)
75 (62–86), n = 57
71 (64–78), n = 174
hSBA, serum bactericidal activity assay using human complement.
a Seroresponse was defined as a post-vaccination hSBA ≥8 for subjects with a pre-vaccination hSBA <4, and an increase in hSBA titer of at least four times the pre-vaccination titer for subjects with a pre-vaccination hSBA ≥4.
Baseline GMTs in the overall population ranged between 2.07 and 11 for serogroups A, C, W, and Y. At 1 month after a single dose of MenACWY-CRM, there were substantial increases in GMT, as evidenced by a 17-fold GMT increase over baseline against serogroup A, a 42-fold increase against serogroup C, a 7-fold increase against serogroup W, and a 15-fold increase against serogroup Y. Generally, an increase in post-vaccination GMTs was noted with increasing age (Table 3).
Table 3hSBA geometric mean titers (95% confidence interval) against serogroups A, C, W, and Y at baseline and at 1 month post-vaccination (day 29), by age group and overall population
2–10 years
11–18 years
19–75 years
Overall
n = 60
n = 60
n = 60
n = 180
Serogroup A
Day 1
2.08 (1.97–2.20)
2.05 (1.95–2.16)
2.07 (1.93–2.21)
2.07 (2.00–2.14)
Day 29
30 (19–47)
50 (30–84)
29 (16–51)
35 (26–47)
Serogroup C
Day 1
2.88 (2.26–3.65)
4.01 (3.00–5.35)
4.14 (3.12–5.49)
3.63 (3.11–4.25)
Day 29
67 (44–101)
191 (117–310)
287 (191–431)
153 (117–199)
Serogroup W
Day 1
9.27 (6.33–14)
14 (9.13–20)
12 (7.70–17)
11 (9.05–14)
Day 29
60 (44–81)
75 (54–105)
116 (71–187)
80 (64–100)
Serogroup Y
Day 1
3.59 (2.75–4.7)
7.87 (5.48–11)
8.69 (5.98–13)
6.26 (5.13–7.65)
Day 29
30 (19–47)
105 (72–155)
173 (97–309)
93 (70–123)
hSBA, serum bactericidal activity assay using human complement.
All enrolled subjects exposed to study vaccination contributed to the safety analyses. Overall, MenACWY-CRM was well tolerated across all age groups. A low incidence of solicited AEs was reported for subjects aged 2–5 years (3.3%) as compared to subjects aged 6–75 years (25.3%). The most commonly reported solicited local reaction was tenderness (3.3%) in the 2–5 years age group, and pain (17.3%) in the 6–75 years age group. None of the subjects in the overall population developed erythema or induration, and there were no severe local reactions (Table 4).
Table 4Number (%) of subjects experiencing any and severe solicited local reactions within 7 days after MenACWY-CRM vaccination, by age group and overall population
In the 2–5 years age group, none of the subjects experienced solicited systemic reactions and there were no reports of fever ≥38 °C or use of analgesics and antipyretics. In the age group 6–10 years, the most commonly reported systemic reactions were headache (6.7%) and malaise (6.7%). In the age group 11–18 years, the most common systemic reaction was headache (8.3%), and one subject reported a severe headache on day 4 after vaccination. In the age group 19–75 years, the most common reaction was also headache (11.7%). A temperature of ≥38 °C was reported in three subjects (2%), there were no reports of high fever ≥40 °C, and 6% of subjects reported use of analgesics/antipyretics (Table 5).
Table 5Number (%) of subjects experiencing any and severe solicited systemic reactions within 7 days after MenACWY-CRM vaccination, by age group and overall
In subjects 2–5 years of age, none reported systemic reactions (change in eating habits, sleepiness, irritability, vomiting, diarrhea, rash), body temperature ≥38.0°C, or use of analgesics/antipyretics.
6–10 years
11–18 years
19–75 years
Overall
n = 30
n = 60
n = 60
n = 150
Arthralgia
Any
1 (3.3%)
1 (1.7%)
0 (0%)
2 (1.3%)
Severe
0 (0%)
0 (0%)
0 (0%)
0 (0%)
Chills
Any
0 (0%)
4 (6.7%)
2 (3.3%)
6 (4%)
Severe
0 (0%)
0 (0%)
0 (0%)
0 (0%)
Headache
Any
2 (6.7%)
5 (8.3%)
7 (11.7%)
14 (9.3%)
Severe
0 (0%)
1 (1.7%)
0 (0%)
1 (0.7%)
Malaise
Any
2 (6.7%)
2 (3.3%)
2 (3.3%)
6 (4%)
Severe
0 (0%)
0 (0%)
0 (0%)
0 (0%)
Myalgia
Any
1 (3.3%)
0 (0%)
2 (3.3%)
3 (2%)
Severe
0 (0%)
0 (0%)
0 (0%)
0 (0%)
Nausea
Any
0 (0%)
1 (1.7%)
1 (1.7%)
2 (1.3%)
Severe
0 (0%)
0 (0%)
0 (0%)
0 (0%)
Fever (≥38.0 °C)
Yes
1 (3.3%)
1 (1.7%)
1 (1.7%)
3 (2%)
Other
Use of analgesics/antipyretics
2 (6.7%)
5 (8.3%)
2 (3.3%)
9 (6%)
Temperature, °C
<38.0
29 (96.7%)
59 (98.3%)
59 (98.3%)
147 (98%)
≥38.0–39.0
1 (3.3%)
1 (1.7%)
1 (1.7%)
3 (2.0%)
>40
0 (0%)
0 (0%)
0 (0%)
0 (0%)
a In subjects 2–5 years of age, none reported systemic reactions (change in eating habits, sleepiness, irritability, vomiting, diarrhea, rash), body temperature ≥38.0 °C, or use of analgesics/antipyretics.
Overall, unsolicited reactions were reported by 10.6% of subjects, of which 2.8% were considered at least possibly related to study vaccination as determined by the investigator.
During the 29-day study period, there was one SAE (pyrexia), which was considered at least possibly related to study vaccination. A 34-year-old woman experienced a mild fever, chills, headache, and body-aches 1 day after vaccination. The woman was admitted to hospital to rule out the possibility of malaria. The laboratory tests were negative for malarial parasites and the discharge diagnosis was fever with chills. The subject recovered completely after 3 days. The assessment of a possible relationship between the SAE and the vaccine was based on a temporal relationship to vaccination. Medication was prescribed for AEs reported in 9.4% of subjects (13.3%, 8.3%, and 6.7% in those aged 2–10 years, 11–18 years, and 19–75 years, respectively). None of the subjects withdrew prematurely from the study due to an AE. There were no deaths.
4. Discussion
Invasive meningococcal disease is a severe, but potentially preventable, healthcare problem worldwide. Vaccines against more than one serogroup have been developed to help provide broader protection against the disease. This phase 3, multi-center, open-label study was the first to evaluate the immunogenicity and safety of a single dose of investigational MenACWY-CRM in healthy Indian subjects aged 2–75 years.
The results demonstrate that MenACWY-CRM induced a robust immune response against all four meningococcal serogroups and was well tolerated within a wide range of age groups. The commonly accepted surrogate endpoint for protection against meningococcal disease is hSBA ≥4.
However, the secondary objective was defined using the even more conservative endpoint of hSBA ≥8 to be consistent with other studies conducted globally. The immunogenic response of a single dose of MenACWY-CRM was demonstrated by the percentage of subjects achieving hSBA ≥8 (72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively). Similar immune responses were seen for the age subgroups 2–10 years, 11–18 years, and 19–75 years.
Regardless of baseline serostatus, the percentages of subjects achieving seroresponse at 1 month following vaccination were 72%, 88%, 55%, and 71% for serogroups A, C, W, and Y, respectively.
Finally, pre-vaccination GMTs increased 17-fold against serogroup A, 42-fold against serogroup C, 7-fold against serogroup W, and 15-fold against serogroup Y. The observed post-vaccination GMTs were generally somewhat higher with increasing age, which has been noted previously.
Comparison of the safety and immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2-10 years of age.
Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.
The seroresponse rates of meningococcal serogroups A, C, and Y are in accordance with the pivotal clinical studies used for licensure of MenACWY-CRM in Europe and the rest of the world.
Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents.
Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.
Comparison of the safety and immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2-10 years of age.
Comparison of the safety and immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2-10 years of age.
which is in agreement with 75%, 84%, and 69% observed for this age group in the present study. For the adolescents aged 11–18 years, the rate of seroresponse against A, C, and Y was 58%, 68%, and 47%,
Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents.
as compared with 76%, 90%, and 69% in the present study. In adults aged 19–55 years, the previously observed percentages of seroresponders following MenACWY-CRM vaccination for serogroups A, C, and Y were 67%, 67%, and 56%,
Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.
compared with the observed 66%, 90%, and 75% in the present study.
Of note, a high percentage of subjects had a pre-vaccination hSBA ≥8 against serogroup W (58% overall). Recently published studies conducted in Russia, Thailand, and Korea obtained similar results.
Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.
Potential reasons for the high pre-vaccination bactericidal antibodies against serogroup W may include nasal colonization or antibody priming with cross-reactive antigens induced by non-meningococcal bacteria.
Comparison of the safety and immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2-10 years of age.
Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents.
Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.
Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.
Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.
the safety data demonstrated that MenACWY-CRM was well tolerated and no safety concerns were identified. A low incidence of solicited AEs was reported for subjects 2–5 years of age (3.3%) as compared to subjects aged 6–75 years (25.7%). There were no solicited systemic AEs in the 2–5 years age group, and only transient and mild to moderate solicited local reactions occurred within the studied population. During the study period, one SAE occurred (pyrexia), for which the assessment of a possible relationship with the vaccine was based on time proximity to vaccination.
Until recently, only unconjugated meningococcal polysaccharide vaccines were licensed in India. Such vaccines can induce a T-cell-independent response for which the duration of the protection is limited, especially in younger age groups, and immune hyporesponsiveness to subsequent doses has been described.
An advantage of conjugate meningococcal vaccines is that they can induce a robust T-cell-dependent response and immunological memory, which is believed to be associated with longer lasting immunity.
The MenACWY-CRM vaccine is also Halal certified, which is relevant to the Indian population.
As a limitation, this study did not include a vaccine comparator or placebo arm. However, previous pivotal trials covering a wide range of age groups have compared MenACWY-CRM with a quadrivalent polysaccharide vaccine and other available conjugated quadrivalent vaccines, and have reported MenACWY-CRM to be non-inferior and well tolerated with a satisfactory safety profile.
Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents.
Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.
Comparison of the safety and immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2-10 years of age.
Overall, a single dose of MenACWY-CRM was well tolerated and elicited a robust immune response against all four serogroups in children, adolescents, and adults in India.
Acknowledgements
The study was funded by Novartis Vaccines and Diagnostics S.r.l., Siena, Italy (a GSK company). The authors are grateful to all of the volunteers who participated in the clinical trial, and thank Patricia de Groot (independent medical writer, CtrlP) and Shanthi Voorn (GlaxoSmithKline B.V., the Netherlands) for providing editorial assistance in the preparation of this manuscript.
Conflict of interest: HV and RJ are either consultant or employee of Novartis Healthcare Pvt. Ltd, Hyderabad, India. PP, MH, CB, and AA were employees of Novartis group companies when the study was conducted and are now employees of GSK group companies. Other authors do not have any conflicts of interest. Novartis Vaccines and Diagnostics S.r.l. is a member of the GSK group of companies.
References
World Health Organization
Meningococcal vaccines: polysaccharide and polysaccharide conjugate vaccines.
Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents.
Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.
Comparison of the safety and immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2-10 years of age.
Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.
Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.
Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.
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