Synflorix suspension for injection 1 dose syringe 0.5 ml with needle No. 1

Instructions Synflorix suspension for injection 1 dose syringe 0.5 ml with needle No. 1

Composition

active substances: one dose (0.5 ml) contains: 1 μg of pneumococcal polysaccharide of serotypes 11.2, 51.2, 6B1.2, 7F1.2, 9V1.2, 141.2, 23F1.2 and 3 μg of pneumococcal polysaccharide of serotypes 41.2, 18C1.3 and 19F1.4;

1 adsorbed on aluminum phosphate – 0.5 mg Al3+

2 conjugated with protein D (derived from a non-typed strain of Haemophilus influenzae) 13 mcg

3 conjugated with tetanus toxoid protein 8 mcg

4 conjugated with diphtheria toxoid protein 5 mcg

Excipients: sodium chloride, water for injections.

Dosage form

Suspension for injection.

Main physicochemical properties: cloudy liquid after shaking. Colorless supernatant and white precipitate after settling.

Pharmacotherapeutic group

Bacterial vaccines. Vaccine for the prevention of pneumococcal infection. Pneumococcal purified polysaccharide antigen and Haemophilus influenzae, conjugated. ATX code J07AL52.

Pharmacological properties

Immunological and biological properties.

Pharmacodynamics.

Epidemiological data

The 10 pneumococcal serotypes included in this vaccine represent the major pathogenic serotypes in Europe, accounting for approximately 56-90% of invasive pneumococcal infections (IPI) in children <5 years of age. In this age group, serotypes 1, 5 and 7F are responsible for 3.3-24.1% of IPIs, depending on the country and the period studied.

Pneumonia of various etiologies is a major cause of childhood morbidity and mortality worldwide. Prospective studies have found that Streptococcus pneumoniae was the probable cause of pneumonia in 30-50% of cases.

Acute otitis media (AOM) is a common childhood disease of various etiologies. Bacteria may be responsible for 60-70% of clinical episodes of AOM. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the most common causes of bacterial AOM worldwide.

Efficacy during clinical trials

In a large-scale, double-blind, cluster-randomized, controlled phase III/IV clinical trial conducted in Finland (FinIP), children were randomized into 4 groups according to two schedules [2-dose (2+1, 3, and 5 months schedule) or 3-dose (3+1, 3, 4, 5 months schedule) primary vaccination with a booster dose at 11 months] to receive either SYNFLORIX vaccine (2/3 clusters) or control hepatitis vaccines (1/3 clusters). In the booster vaccination cohorts, children aged 7 to 11 months at the time of the first dose of vaccine received SYNFLORIX or a hepatitis B control vaccine according to a 2-dose primary vaccination schedule followed by a booster dose, and children aged 12 to 18 months at the time of the first vaccination received 2 doses of SYNFLORIX or a hepatitis A control vaccine. The median follow-up period after the first dose was 24 to 28 months for invasive pneumococcal infection and diagnosed hospital-acquired pneumonia. In the nested study, the children were followed up for up to 21 months to assess the impact on nasopharyngeal carriage and physician-diagnosed acute otitis media reported by parents.

In a large, double-blind, randomized, controlled phase III clinical trial (Clinical Otitis Media and Pneumonia Study - COMPAS) conducted in Argentina, Panama and Colombia, healthy infants aged 6 to 16 weeks received either SYNFLORIX or a hepatitis B control vaccine at 2, 4 and 6 months, followed by SYNFLORIX or a hepatitis A control vaccine at 15 to 18 months of age.

Invasive pneumococcal infections (including sepsis, meningitis, pneumonia with bacteremia, and bacteremia)

Efficacy/effectiveness in a cohort of infants under 7 months of age at enrollment

Vaccine efficacy or effectiveness (EV) was demonstrated in preventing culture-confirmed invasive pneumococcal infection (IPI) caused by vaccine pneumococcal serotypes when SYNFLORIX was administered to children in the 2+1 or 3+1 regimen in the FinIP study or the 3+1 regimen in the COMPAS study (see Table 1).

Table 1

Number of cases of IPI caused by vaccine serotypes and vaccine efficacy (FinIP) or efficacy (COMPAS) in infants <7 months of age at study entry who received at least one dose of vaccine (total vaccinated infant cohort)

IPI: Invasive pneumococcal infections

EV: Vaccine efficacy in a clinical trial (FinIP) or Vaccine efficacy in a clinical trial (COMPAS)

N: number of subjects in the group; CI: Confidence interval.

(1) In the FinIP study, other serotypes causing IPI included 7F (1 case in the SYNFLORIX 2+1 clusters), 18C, 19F and 23F (1 case per serotype) in the control clusters. In the COMPAS study, serotypes 5 (2 cases), 18C (4 cases) and 23F (1 case) were also identified in the control group in addition to serotypes 6B and 14.

(2) 2 groups of control clusters of infants were combined

(3) p-value < 0.0001

(4) p-value = 0.0009

(5) in the per-protocol (ATP) cohort, vaccine efficacy was 100% (95% CI: 74.3; 100; 0 cases compared to 16)

In the FinIP study, the overall vaccine efficacy against culture-confirmed IPI was 100% (95% CI: 85.6; 100; 0 cases vs. 14) for the 3+1 vaccination schedule, 85.8% (95% CI: 49.1; 97.8; 2 cases vs. 14) for the 2+1 vaccination schedule, and 93.0% (95% CI: 74.9; 98.9; 2 cases vs. 14) regardless of the primary vaccination schedule. In the COMPAS study, the overall vaccine efficacy was 66.7% (95% CI: 21.8; 85.9; 7 cases vs. 21).

Vaccine effectiveness after vaccination tour

Among 15,447 children in the round-vaccinated cohorts, no culture-confirmed cases of IPI were identified in the SYNFLORIX vaccine groups, while 5 cases of IPI caused by vaccine serotypes (serotypes 4, 6B, 7F, 14, and 19F) were observed in the control groups.

Pneumonia

The efficacy of the pneumonia vaccine was evaluated in the COMPAS clinical trial. The median duration of follow-up after vaccination from 2 weeks after dose 3 in the per-protocol (ATP) cohort was 23 months (range 0 to 34 months) for the interim analysis and 30 months (range 0 to 44 months) for the final analysis of the study. At the end of follow-up in the per-protocol (ATP) cohort for the interim analysis and the final analysis of the study, the median age of the children was 29 months (range 4 to 41 months) and 36 months (range 4 to 50 months), respectively. The proportion of subjects who received a booster dose in the ATP cohort was 92.3% in both analyses.

The efficacy of SYNFLORIX in preventing the first episode of probable bacterial community-acquired pneumonia (CAP) from 2 weeks after the 3rd dose was demonstrated in an interim analysis (by event occurrence; primary endpoint) in the ATP cohort (p ≤ 0.002).

Probable bacterial pneumonia (P-PN) was defined as a radiologically confirmed case of pneumonia in which either alveolar infiltrate/pleural effusion or non-alveolar infiltrates were observed on radiological examination, provided that the C-reactive protein (CRP) level was ≥ 40 mg/L.

The efficacy of the vaccine against B–NP, demonstrated in the interim analysis, is presented below (Table 2).

Table 2

Number and percentage of individuals with first episodes of B-NP observed from 2 weeks after the 3rd dose of SYNFLORIX vaccine or control vaccine, and vaccine efficacy (ATP cohort)

N is the number of people in the group.

n/% – number/percentage of individuals who had their first episode of B-NP at any time starting 2 weeks after the 3rd dose.

CI – confidence interval.

In the interim analysis (ATP cohort), vaccine efficacy against the first episode of PN with alveolar infiltrate or pleural effusion (WHO definition of community-acquired pneumonia) was 25.7% (95% CI: 8.4; 39.6) and against the first episode of clinically suspected PN requiring referral for radiological confirmation was 6.7% (95% CI: 0.7; 12.3).

At the final analysis (ATR cohort), vaccine efficacy (first episodes) against B-PN was 18.2% (95% CI: 4.1; 30.3), against WHO-defined NP was 22.4% (95% CI: 5.7; 36.1), and against clinically suspected NP requiring referral for radiological confirmation was 7.3% (95% CI: 1.6; 12.6). Vaccine efficacy was 100% (95% CI: 41.9; 100) against bacteremic pneumococcal pneumonia or empyema caused by vaccine serotypes. The protective efficacy against B–HP before and at or after the booster dose was 13.6% (95% CI: -11.3; 33.0) and 21.7% (95% CI: 3.4; 36.5), respectively. The protective efficacy of the vaccine against HP according to the WHO definition before and at or after the booster dose was 15.1% (95% CI: -15.5; 37.6) and 26.3% (95% CI: 4.4; 43.2), respectively.

The reduction in the incidence of B–NP and WHO-defined NP was greatest in children aged < 36 months (vaccine efficacy 20.6% (95% CI: 6.5; 32.6) and 24.2% (95% CI: 7.4; 38.0), respectively). The vaccine efficacy results in children aged > 36 months suggest a weakening of protection. The duration of protection against B–NP and WHO-defined NP in children aged 36 months and older is currently not established.

In the FinIP study, vaccine efficacy in reducing hospital-acquired pneumonia (defined by ICD-10 codes for pneumonia) was 26.7% (95% CI: 4.9, 43.5) in infants who received the 3+1 vaccine and 29.3% (95% CI: 7.5, 46.3) in infants who received the 2+1 vaccine. In the booster vaccination series, vaccine efficacy was 33.2% (95% CI: 3.0, 53.4) in the 7- to 11-month-old cohort and 22.4% (95% CI: -8.7, 44.8) in the 12- to 18-month-old cohort.

Acute otitis media (AOM)

Two efficacy studies, COMPAS and POET (Pneumococcal Otitis Media Prevention Efficacy Study), were conducted, which studied pneumococcal conjugate vaccines containing Haemophilus influenzae type B protein D: SYNFLORIX and an investigational 11-valent conjugate vaccine (which additionally contains serotype 3), respectively.

In the COMPAS study, 7,214 individuals [total vaccinated cohort (TVC)] were included in the analysis of the efficacy of GSO prevention, 5,989 of whom were included in the ATR cohort (Table 3).

Table 3

Efficacy of the GMO vaccine(1) in the COMPAS study

CI – confidence interval.

(1) The first episode.

(2) The maximum follow-up period was 40 months from the start 2 weeks after the third dose of the primary vaccination course.

(3) Not statistically significant based on pre-specified criteria (one-sided p = 0.032). However, in the SVC, vaccine efficacy against the first clinical episode of SSI was 19% (95% CI: 4.4, 31.4).

(4) Not statistically significant.

In another large randomized, double-blind study (POET) conducted in the Czech Republic and Slovakia, 4,907 infants (ATP cohort) received either the 11-valent investigational vaccine (11Pn-PD) containing the 10 serotypes of SYNFLORIX vaccine plus serotype 3, for which efficacy had not been demonstrated), or a control vaccine (hepatitis A vaccine) according to a vaccination schedule at 3, 4, 5 and 12–15 months.

The efficacy of the 11 Pn-PD vaccine against the first episode of SSI caused by the vaccine serotype was 52.6% (95% CI: 35.0; 65.5). Serotype-specific efficacy against the first episode of SSI was demonstrated for serotypes 6B (86.5%; 95% CI: 54.9; 96.0), 14 (94.8%; 95% CI: 61.0; 99.3), 19F (43.3%, 95% CI: 6.3; 65.4) and 23F (70.8%, 95% CI: 20.8; 89.2). For the other vaccine serotypes, the number of SSI cases was too limited to draw any conclusion on efficacy. The efficacy against any episode of SSI caused by any pneumococcal serotype was 51.5% (95% CI: 36.8, 62.9). The efficacy of the vaccine against the first episode of SSI caused by NTHi was 31.1% (95% CI: -3.7, 54.2, not significant). The efficacy of the vaccine against any episode of SSI caused by NTHi was 35.3% (95% CI: 1.8, 57.4). The estimated efficacy of the vaccine against any clinical episode of otitis media regardless of etiology was 33.6% (95% CI: 20.8, 44.3).

Based on the concept of an “immunological bridge”, it is expected that, taking into account the functional vaccine response (OPA) data to the 11-valent vaccine used in the POET study, SYNFLORIX provides similar protective efficacy against SSI of pneumococcal etiology.

An increase in the incidence of SSI caused by other bacterial pathogens or non-vaccine/non-vaccine serotypes was not observed in either the COMPAS study (based on multiple reports) or the POET study.

Efficacy against physician-diagnosed, parent-reported SSI was studied in a nested study within the FinIP study. Vaccine efficacy was 6.1% (95% CI: -2.7, 14.1) for the 3+1 vaccination schedule and 7.4% (95% CI -2.8, 16.6) for the 2+1 vaccination schedule for physician-diagnosed SSI in the vaccinated infant cohort.

Impact on nasopharyngeal carriage (NFC)

The effect of SYNFLORIX on nasopharyngeal carriage was studied in 2 double-blind, randomized studies with inactive controls: the FinIP nested study in Finland (5,023 subjects) and COMPAS (1,700 subjects).

In both COMPAS and the Finnish Nested Study, SYNFLORIX reduced carriage of vaccine pneumococcal serotypes with a clear increase in non-vaccine serotypes (except vaccine-related) after the booster dose. The results were not statistically significant for all analyses performed within the COMPAS study. However, there was an overall trend towards a reduction in total pneumococcal carriage.

A clinical study evaluated NFN in HIV-positive children (N = 83) and HIV-negative children born to HIV-positive mothers (N = 101) and compared with HIV-negative children born to HIV-negative mothers (N = 100). The effect of HIV or the presence of HIV infection did not alter the effect of SYNFLORIX on pneumococcal carriage up to 24–27 months of age, i.e. up to 15 months after booster vaccination.

Efficacy from post-marketing surveillance

In Brazil, SYNFLORIX was introduced into the National Immunization Program (NIP) using a 3+1 schedule in infants (2, 4, 6 months of age and a booster dose at 12 months) with a booster dose at 2 years of age. Based on a follow-up period of almost 3 years after the introduction of SYNFLORIX into the immunization program, a matched case-control study showed a significant reduction in culture- or PCR-confirmed IPI due to any vaccine serotype and IPI due to individual serotypes 6B, 14 and 19A.

Table 4

Summary of the efficacy of SYNFLORIX vaccine against IPI in Brazil

(1) IPI confirmed by culture or PCR.

(2) Adjusted efficacy is the percentage reduction in IPI in the group of patients vaccinated with SYNFLORIX compared to the group of unvaccinated patients, taking into account confounding factors.

(3) The analysis included cases of IPI confirmed by culture or PCR, caused by vaccine serotypes 4, 6B, 7F, 9V, 14, 18C, 19F and 23F.

(4) Individual serotypes for which statistical significance was achieved in the efficacy analysis with control for confounding factors (multiplicity adjustment not performed).

In Finland, SYNFLORIX was introduced into the NPI using a 2+1 schedule in infants (at 3.5 months of age and a booster dose at 12 months) without a booster vaccination series. Comparison of data before and after introduction into the NPI showed a significant reduction in the incidence of any culture-confirmed IPI, IPI caused by any vaccine serotype, and IPI caused by serotype 19A.

Table 5

Incidence of IPI and relative reduction in IPI incidence in Finland

(1) Relative incidence reduction indicates how much the incidence of IPD in children ≤5 years of age in the SYNFLORIX vaccination cohort (followed for 3 years after the introduction of the NPY) decreased compared to unvaccinated historical cohorts of the same age and season (each cohort was followed for 3 years before the introduction of SYNFLORIX in the NPY).

(2) Culture-confirmed cases of IPI caused by vaccine serotypes 1, 4, 6B, 7F, 9V, 14, 18C, 19F and 23F were included in the analysis.

In Quebec, Canada, after 4.5 years of use of the 7-valent vaccine (PCV), SYNFLORIX was introduced into the infant immunization program (2 primary doses in infants <6 months of age and a booster dose at 12 months of age). Based on a 1.5-year follow-up after the introduction of SYNFLORIX into the immunization program with vaccination coverage of 90% of children in this age group who were eligible for immunization, there was a decrease in the incidence of IPI caused by vaccine serotypes (mainly due to a change in the incidence of disease caused by serotype 7F), while there was no increase in the incidence of IPI caused by non-vaccine serotypes. The overall incidence of IPI was 35/100,000 person-years in the SYNFLORIX vaccination cohorts and 64/100,000 person-years in the 7-valent vaccine (PCV) vaccination cohorts, a statistically significant difference (p = 0.03). It is not possible to draw conclusions about a direct cause-and-effect relationship based on observational studies of this type.

Immunogenicity data

No less immunological efficacy compared to the 7-valent vaccine (PCV)

In a head-to-head comparison study with 7-valent vaccine (PCV), non-inferiority of the immune response to SYNFLORIX, as determined by ELISA, was demonstrated for all serotypes except 6B and 23F (upper limit of the 96.5% CI for between-group differences > 10%). For serotypes 6B and 23F, 65.9% and 81.4% of children vaccinated at 2, 3 and 4 months of age, respectively, achieved a threshold antibody level (i.e. 0.20 µg/ml) one month after the third dose of SYNFLORIX compared to 79.0% and 94.1% of children, respectively, after three doses of 7-valent vaccine (PCV). The clinical significance of these differences is unknown, as the efficacy of SYNFLORIX against IPI caused by serotype 6B was demonstrated in a double-blind clinical trial using cluster randomization (see Table 1).

The percentage of vaccinees reaching the threshold for the three additional serotypes of SYNFLORIX vaccine (1, 5 and 7F) was 97.3%, 99.0% and 99.5%, respectively, and was at least as good as the overall immune response induced by the 7-valent vaccine (PCV) against the 7 common serotypes (95.8%).

Table 6

Comparative analysis between 7-valent vaccine (PCV) and SYNFLORIX vaccine in the percentage of subjects with antibody concentrations ≥ 0.20 μg/ml one month after the 3-dose primary vaccination course

The geometric mean concentrations (GMCs) of antibodies induced by SYNFLORIX against the seven common serotypes after primary vaccination were lower than those induced by the 7-valent vaccine (PCV). The GMCs before booster vaccination (8-12 months after the last dose of the primary vaccination course) were generally similar for both vaccines. After the booster dose, the GMCs induced by SYNFLORIX were lower for most of the serotypes included in the 7-valent vaccine (PCV).

In the same study, SYNFLORIX was shown to induce functional antibodies to all vaccine serotypes. For each of the seven common serotypes, 87.7% to 100% of subjects immunized with SYNFLORIX and 92.1% to 100% of subjects immunized with the 7-valent vaccine (PCV) achieved an ORA (Serotype-Specific Pneumococcal Opsonophagocytic Activity) titer ≥ 8 one month after the third dose. The difference between the two vaccines in terms of the percentage of subjects with ORA titers ≥ 8 was <5% for all common serotypes, including 6B and 23F. The geometric mean titers (GMT) of ORA antibodies induced by SYNFLORIX vaccine after primary vaccination and booster vaccination were lower than the titers induced by the 7-valent vaccine (PCV) for the seven common serotypes, except for serotype 19F.

For serotypes 1, 5 and 7F, the number of individuals immunized with SYNFLORIX with an ORA titer ≥ 8 was 65.7%, 90.9% and 99.6% after the primary vaccination course and 91.0%, 96.3% and 100% after the booster dose, respectively. The ORA response to serotypes 1 and 5 was less pronounced than the response to each of the other serotypes. The significance of these results for protective efficacy is unknown. The immune response to serotype 7F was in the same range as for the seven serotypes common to both vaccines.

SYNFLORIX vaccine was also shown to induce an immune response to the cross-reactive serotype 19A in 48.8% (95% CI: 42.9; 54.7) of vaccinees, reaching an OPA titer ≥ 8 one month after booster vaccination.

Administration of a fourth dose (booster) in the second year of life induced an anamnestic immune response, measured by ELISA and OPA assay, to the vaccine serotypes and the cross-reactive serotype 19A, demonstrating induction of immune memory after the primary three-dose vaccination course.

Additional immunogenicity data

Infants aged 6 weeks to 6 months:

Primary vaccination schedule with 3 doses

In clinical studies, the immunogenicity of SYNFLORIX was evaluated after a 3-dose primary vaccination course (6,941 subjects) administered according to different schedules (including children aged 6–10–14 weeks, 2–3–4, 3–4–5 or 2–4–6 months) and after a fourth (booster) dose (5,645 subjects) administered no earlier than 6 months after the last dose of the primary vaccination course and at the age of 9 months and older. Overall, comparable immune responses to vaccination were observed for the different vaccination schedules, although a slightly higher immune response was observed for the 2–4–6 months vaccination schedule.

In clinical studies, the immunogenicity of SYNFLORIX vaccine was evaluated after a 2-dose primary vaccination course (470 subjects) administered according to different schedules (including children aged 6–14 weeks, 2–4 or 3–5 months), and after a third (booster) dose (470 subjects) not earlier than 6 months after the last dose of the primary vaccination course, and at the age of 9 months and older.

A clinical study evaluated the immunogenicity of SYNFLORIX vaccine when administered as a 2-dose or 3-dose primary vaccination schedule in study participants in four European countries. Although there was no significant difference in the percentage of subjects with antibody concentrations ≥ 0.20 μg/ml (ELISA) between the two groups, the percentage was lower for serotypes 6B and 23F compared to the other vaccine serotypes. The percentage of subjects with OPA titers ≥ 8 in the 2-dose vaccination schedule group compared to the 3-dose vaccination schedule group was lower for serotypes 6B, 18C and 23F (74.4%, 82.8%, 86.3% and 88.9%, 96.2% and 97.7% for the 2-dose and 3-dose vaccination schedules, respectively). Overall, the persistence of the immune response to booster vaccination at 11 months of age was lower in children who received a two-dose primary vaccination course. A booster response was observed for each vaccine serotype with both schedules, indicating immunological priming (see Table 7 and Table 8). After booster vaccination, fewer children with OPA3 titers ≥8 were observed in the 2-dose schedule group for serotypes 5 (87.2% versus 97.5% for the 3-dose schedule) and 6B (81.1% versus 90.3%), all other results were comparable.

Table 7

Percentage of subjects with antibody concentrations ≥ 0.20 μg/mL one month after the primary vaccination course and one month after the booster dose following the 2-dose primary vaccination schedule

Table 8

Percentage of subjects with antibody concentrations ≥ 0.20 μg/mL one month after the primary vaccination course and one month after the booster dose following the 3-dose primary vaccination schedule

For the cross-reactive serotype 19A, similar ELISA antibody GMCs were observed after primary vaccination and after booster vaccination with the 2-dose schedule [0.14 μg/ml (95% CI: 0.12, 0.17) and 0.73 μg/ml (95% CI: 0.58, 0.92)] and the 3-dose schedule [0.19 μg/ml (95% CI: 0.16, 0.24) and 0.87 μg/ml (95% CI: 0.69, 1.11)]. The percentage of subjects with OPA titers ≥ 8 and GMTs observed after primary vaccination and booster vaccination were lower with the 2-dose schedule than with the 3-dose schedule. When using both regimens, a response to booster vaccination was observed, indicating an immunological response to the primary vaccination.

In a clinical study conducted in South Africa, the immunogenicity of SYNFLORIX was evaluated after a 3-dose (6-10-14 weeks of age) or 2-dose (6-14 weeks of age) primary vaccination and a subsequent booster at 9-10 months of age. After primary vaccination, the percentage of subjects achieving the threshold antibody concentration and with OPA titers ≥ 8 to the vaccine serotypes was similar after 2-dose and 3-dose vaccination, except for a lower percentage of subjects with OPA titers to serotype 14. Antibody GMCs and OPA GMTs were lower after the 2-dose primary vaccination for most vaccine serotypes.

For the cross-reactive serotype 19A, the same percentage of study participants achieved the threshold antibody concentration and OPA titers ≥ 8, and after primary vaccination, the same antibody GMCs and OPA GMTs were observed in both groups.

Overall, prior to booster vaccination, the persistence of the immune response was less pronounced in the 2-dose primary vaccination group compared to the 3-dose primary vaccination group for most vaccine serotypes and was similar for serotype 19A.

Revaccination at the age of 9–10 months

In a study conducted in South Africa, a booster dose administered at 9–10 months of age resulted in a marked increase in antibody GMCs and OPA GMTs to each vaccine serotype and serotype 19A in the 2-dose and 3-dose primary vaccination groups, indicating an immunological response to the primary vaccination.

Booster vaccination at 9–12 months compared to booster vaccination at 15–18 months

In a clinical study conducted in India, evaluation of booster doses administered at 9–12 or 15–18 months of age, respectively, in 66 and 71 children after primary vaccination at 6, 10, and 14 weeks, indicated no differences between groups in antibody GMCs. The group revaccinated at 15–18 months of age had higher OPA GMTs to most vaccine serotypes and serotype 19A. However, the clinical significance of these findings is unknown.

Immune memory

In a follow-up study of subjects from the European study evaluating the 2-dose and 3-dose vaccination schedules, persistence of antibodies was demonstrated in children aged 36-46 months who received a 2-dose primary vaccination course followed by a booster, with at least 83.7% of children remaining seropositive to the vaccine serotypes and the cross-reactive serotype 19A. In the group receiving a 3-dose primary vaccination course followed by a booster, at least 96.5% of children remained seropositive to the vaccine serotypes and 86.4% to serotype 19A. After a single dose of SYNFLORIX at the age of four as a challenge dose, the fold increase in antibody GMCs determined by ELISA and OPA GMTs before and after vaccination were similar in those primed with the 2-dose and 3-dose schedules. These results suggest immunological memory in primarily vaccinated individuals to all vaccine serotypes and the cross-reactive serotype 19A.

Previously unvaccinated infants and children ≥ 7 months of age:

The immune response induced by SYNFLORIX vaccine in previously unvaccinated older children was evaluated in three clinical studies.

The first clinical study evaluated immune responses to vaccine serotypes and cross-reactive serotype 19A in children aged 7–11 months, 12–23 months, and 2–5 years:

Children aged 7-11 months received 2 doses of primary vaccination followed by a booster dose in the second year of life. The immune response following a booster dose of SYNFLORIX in this age group was generally similar to that observed following a booster dose in children who received 3 doses of vaccine before the age of 6 months.

In children aged 12-23 months, the immune response induced by two doses of SYNFLORIX was comparable to that observed after three doses in children aged <6 months, with the exception of vaccine serotypes 18C and 19F, as well as serotype 19A, for which the immune response was higher in children aged 12-23 months.

In children aged 2–5 years who received a single dose of vaccine, the ELISA antibody GMCs for the 6 vaccine serotypes as well as serotype 19A were similar to those achieved after a 3-dose primary vaccination schedule in children aged <6 months, but were lower than those achieved after a 3-dose primary vaccination schedule in children aged <6 months.