Document text
VAP00027
Immunogenicity and Safety of Quadrivalent Recombinant
Influenza Vaccine (RIV4) in Children and Adolescents
Aged 9 to 17 Years and Adults Aged 18 to 49 Years
For the Advisory Committee of Immunization Practices (ACIP) Influenza Working Group
MAT-US-2504669 P v3.0 EXP 28 APR 2026Pedro Folegatti – Global Clinical Development Director (Presenter)
Thinus Marais – Medical Head: Influenza & COVID, Vaccines North America
Presenter’s disclosures
Pedro Folegatti , MD DTM&H MSc Dphil
is a full -time employee of Sanofi and may hold shares
in the company
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Recombinant technology ensures sequence integrity of
antigens consistent with WHO -identified strains for
seasonal vaccine formulation
BEVS, baculovirus expression vector system; CBER, Center for Biologics Evaluation and Research; HA, hemagglutinin; MDCK, Madin -Darby Canine Kidney; NIBSC, National Institute for Biological Standards and
Control; rHA, recombinant haemagglutinin; rHA0, recombinant influenza virus hemagglutinins; SF+, spodoptera frugiperda (fall armyworm) -positive ; TGA, Therapeutic Goods Administration ; VRBPAC, Vaccines and
Related Biological Products Advisory Committee; WHO, World Health Organization.
Reference : Arunachalam AB, et al. NPJ Vaccines .2021;6:144. Selection of virus strains
for vaccine composition
(WHO, VRBPAC)
Virus genomeHA proteinWild-type virus
RIV is produced using the exact genetic
sequence of the HA protein derived from the WHO
selected influenza strains; no live virus is used in
the manufacturing processIn this novel production platform,
rHA is expressed in insect cells
using BEVSrHA molecules are subsequently extracted from
the infected insect cells and purified from the
clarified cell extract before formulationInactive
virus
Virus
componentsPurify and
formulate
Formulated
vaccineDevelop seed virus
(CBER, NIBSC, TGA)
Egg-adapted
seed virus
Cell-adapted
seed virus Infect egg/cells
with flu virusGrow and
harvest virus
Embryonated
chicken egg
Replicated
virusMDCK cells
(dog kidney)EGG CELL
Produce, harvest
HA proteinPurify and
formulate
Formulated
vaccineHA protein
(rHA0)HA protein sequenceAdd HA gene to
BaculovirusInfect SF+cells
with Baculovirus
SF+cells
(caterpillar)Baculovirus
with HA geneRECOMBINANT
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Safety and efficacy of RIV in clinical studies and
real-world data
GMT, geometric mean titers; IIV4, quadrivalent inactivated influenza vaccine; RIV3, trivalent recombinant influenza vaccine; RIV4, quadrivalent recombi nant influenza vaccine; SC, seroconversion; US, United States
References: 1. Dunkle LM, et al. N Engl J Med . 2017;376(25):2427 -36. 2. Dunkle LM, et al. J Infect Dis. 2017;216(10):1219 -26. 3. Prevention and Control of Influenza with Vaccines: Interim Recommendations of the
Advisory Committee on Immunization Practices (ACIP), 2013 . Accessed August 2024. 4. Flublok ® Influenza Vaccine. Product Insert.Clinical data (RIV4)
•2 Phase III studies
–Adults 50 years of age and older1 during a season with predominantly antigenically drifted H3N2 strains
•RIV4 provided 30% (95% CI, 10 to 47) to 43% (95% CI, 21 to 59) enhanced protection against influenza
disease vs IIV4
–Adults 18 to 49 years of age2
•Non-inferior to the same IIV4 comparator vaccine for 3 of 4 influenza (SC rates and GMTs)
First license and recommendation
•RIV3 was first licensed in the US in 2013, followed by approval of RIV4 in 2016 for adults ≥18 years of age
•ACIP recommends use of recombinant influenza vaccination from 20133
Real -world safety data:
•~38 million doses of RIV3 and RIV4 distributed cumulatively (Sanofi internal data as of 31 Jan 2024)
•Established clinical safety profile, well tolerated with no safety concerns4
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Study design
•Phase III parallel, multi -center , open -label, non -randomized
•Immuno -bridging study
•36 centers in Europe (Spain, Poland, Czech Republic) and
the United States
•2022/2023 northern hemisphere influenza
Study population:
•Healthy children & adults; n=1334
•Aged 9 -49 years
Intervention:
•To receive a single dose of:
RIV4 (9 to 17y)
n = 667RIV4 (18 to 49y)
n = 667
Objectives & endpoints
Primary:
•To demonstrate the non -inferior HAI immune response of RIV4 for 4
strains in participants aged 9 to 17 years vs participants aged 18 to
49 years
–HAI titers at D29
–Seroconversion rates
Secondary:
•To describe the safety profile of RIV4 vaccine in all participants and
by age group
–Solicited & Unsolicited AEs
–MAAEs
–SAEs and AESIs
•To describe HAI immune responses induced by RIV4
Trial design (1/2)
Ab, antibody; AE, adverse event; AESI, adverse events of special interest; HAI, hemagglutination inhibiting antibody; MAAEs, medically attended adverse events; NAb, neutralizing antibody; RIV4, recombinant influenza
vaccine quadrivalent; SAEs, serious adverse events; US, United States.
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Trial design (2/2)
AEs, adverse events; AESIs, adverse events of special interest; CI, confidence interval; D, Day; PC, Phone Call; GMTs, geomet ric mean titers; MAAEs, medically attended adverse event; NI, non -inferiority; RIV4,
quadrivalent recombinant influenza vaccine; SAEs, serious adverse events; VAC, vaccinationKey exclusion criteria
•Receipt of any vaccine in the 4 weeks before or after
enrolment
–COVID -19 vaccines were allowed within 2 weeks
(before or after enrolment)
•Influenza vaccine receipt in the 6 months preceding
enrolment
Statistical considerations
•Overall study power of 80%
–type II error <20% for the 8 NI tests (GMTs and
SC on 4 strains)
•Non-Inferiority Margin
–Lower bound of the two -sided 95% CI of the ratio
of GMTs between groups >0.667 for each strain
–Lower bound of the two -sided 95% CI of
seroconversion rates ≥ -10% for the 4 strains
VAC 1 6-months follow -up
Visit/Contact V01 PC1 V02 PC2
Time (Day) D01 D09 D29 D181
Unsolicited
Systemic
AEsImmunogenicity
Safety Solicited
AEsUnsolicited
AEs, MAAEsSAEs, AESIs
RIV4
Blood samplingGraphical Study design
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7 OPTIONS XII Congress, Brisbane, Australia; 29 September – 2 October 2024 Participant disposition
Enrolment period
27 October 2022 – 01 May 2023
N, number of participants; V, visitN planned = 1334
N enrolled = 1308
9 to 17 years old
N planned = 66718 to 49 years old
N planned = 667
N at V01 = 648
N blood sample = 641
N vaccinated = 641N at V01 = 660
N blood sample = 658
N vaccinated = 658
Discontinued N = 19
•Protocol deviation = 6
•Withdrawal by subject = 2
•Withdrawal by parent/guardian = 2
•Lost to follow up = 9Discontinued N = 22
•Adverse event = 1
•Protocol deviation = 3
•Withdrawal by subject = 8
•Lost to follow up = 10*
N at V02 = 629
N blood sample = 626N at V02 = 638
N blood sample = 634
N completed the active phase = 629 N completed the active phase = 636*
Total completed active phase = 1265
N at 6 -month
follow up = 611N at 6 -month
follow up = 613Discontinued N = 2
•Adverse event = 1
•Withdrawal by subject = 1
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8 OPTIONS XII Congress, Brisbane, Australia; 29 September – 2 October 2024 Baseline Characteristics
Overall, there were more females than males (653 females [53.7%] and 562 males [46.3%])
and the male/female ratio was 0.86
The overall mean age of participants was 23.5 years ( ± 12.5)
•13 years ( ±2.48) in the 9 -17s and 34 years in the 18 -49s ( ±9.20)
Most participants (87.0%) were of “Not Hispanic or Latino” ethnicity
Most participants were White (77.4%), followed by Black or African American
participants (18.9%)
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Primary objective met
Non-inferiority of immune response: GMTs at Day 29
•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for
GMT ratios of all 4 strains
GMTs at D29 after vaccination of 9 to 17 years vs 18 to 49 years
CI, confidence interval; GMT, geometric mean titers; HAI, hemagglutination inhibition; RIV4, quadrivalent recombinant influenza vaccine1946
(1795; 2109)1975
(1771; 2202)
405
(362; 452)1941
(1779; 2118)982
(881; 1094) 604
(531; 687)258
(233; 285)1593
(1477; 1717)
110100100010000
A/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean of HAI antibody
titer (95% CI)
Influenza strain
9–17 years (D29) 18–49 years (D29)D29 GMT Ratios (95% CI): 9 to 17 years vs 18 to 49 years
1.98 ( 1.73; 2.27) 3.27 ( 2.76; 3.87) 1.57 ( 1.35; 1.82) 1.22 ( 1.09; 1.37)
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•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for
seroconversion of all 4 strains of influenza
9 to 17 years minus 18 to 49 years
Antigen/
strainDifference (%) (95% CI) Non-inferiority§
A/H1N1 1.92 (-2.78; 6.62) Y
A/H3N2 -0.59 (-4.41; 3.23) Y
B/Victoria 3.29 (-1.57; 8.14) Y
B/Yamagata 14.3 (9.17; 19.3) Y
M, number of participants with available data for the considered endpoint; N, total number of participants included in the st udy; §Non-inferiority for SC rates is demonstrated if the lower limit of
the 2-sided 95% CI is ≥ -10% for the 4 strainsImmunogenicity primary objective: Non -inferiority of immune response in terms of seroconversion rates after
vaccination of 9 to 17 years vs 18 to 49 years
CI, confidence interval; RIV4, quadrivalent recombinant influenza vaccine; SC, seroconversionPrimary objective met
Non-inferiority of immune response: Seroconversion
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Safety overview
AR, adverse reactions ; AESI, adverse event of special interest; CI, confidence interval; MAAE, medically attended adverse event; SAE, serious adverse eventDuring the study, 10 participants (0.8%) reported at least 1 SAE and 66 participants (5.1%)
reported at least 1 MAAE. None of the SAEs and MAAEs were considered as related to the
vaccine
No deaths and no AESIs were reported during the study
No substantial differences in safety profile was observed between groups
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Solicited reactions within 7 days of vaccinations
•Most solicited reactions were of Grade 1 or Grade 2 intensity, started within D1 -D4, and resolved (spontaneously) after 1 -3
days
•Within 28 days of vaccination, 0.9% of participants in both age groups experienced at least 1 unsolicited injection site AR
rated as Grade 3
•Grade 3 solicited injection site reactions consisted predominantly of swelling in 9 participants of 9 to 17 years group
(1.5%) and induration in 5 participants of 18 to 49 years (0.8%)
•Grade 3 solicited systemic reactions consisted predominantly of headache and malaise reported by 16 participants (2.6%,
each) in 9 to 17 years group. Grade 3 malaise was reported by 10 participants (1.6%) in 18 to 49 years groups
AR, adverse reaction; D, day44.3
6.535.6
3.129.6
4.652.9
4.640.8
1.436.2
3.1
0102030405060
Solicited reaction Grade 3 solicited reaction Solicited injection site
reactionGrade 3 injection site
reactionSolicited systemic reaction Grade 3 systemic reactionParticipants experiencing at
least one (%)
9 to 17 years 18 to 49 yearsSummary of solicited reactions within 7 days after vaccine injection
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Solicited injection site reactions after vaccine injection
AR, adverse reaction
Summary of solicited injection site reactions after vaccination
22.22.81.31.81.5
11.30.61.00.50.5
0.81.11.50.80.5
0 5 10 15 20 25Injection site painInjection site erythemaInjection site swellingInjection site indurationInjection site bruising
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 131.21.30.81.90.5
8.70.91.40.60.2
0.30.50.50.80.5
0 5 10 15 20 25 30 35Injection site painInjection site erythemaInjection site swellingInjection site indurationInjection site bruising
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 12.5
3.1
3.8
4.5
34.31.2
3.3
2.7
2.7
40.29 to 17 years
18 to 49 years
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Solicited systemic reactions after vaccine injection
AR, adverse reaction
1.00.7
16.1
2.88.55.79.13.3
7.57.88.83.4
1.02.62.61.50.7
0 2 4 6 8 10FeverHeadacheMalaiseMyalgiaChills
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 11.19.45.29.43.1
0.212.19.89.92.5
0.51.31.60.90.6
0 2 4 6 8 10 12 14FeverHeadacheMalaiseMyalgiaChills
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 16.2
20.2
16.6
22.8
1.89 to 17 years
18 to 49 years
1.0
0.87.4
19.4
18.6
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13 SAEs reported in the study:
All events classified as unrelated by Sponsor and
Investigator
*All participants reporting Psychiatric Disorders SAEs had past medical history of
mental health disorders prior to enrollment
^Neurology review attributed event to amphetamine use, sleep deprivation and
metabolic disorder
MAT-US-2504669 P v3.0 EXP 28 APR 2026•7 participants reported 9 SAEs
•Within 28 days
•Major Depression and Intentional
Overdose*
•Gastric Cancer Recurrent
•Suicidal Ideation*
•Seizure^
•Acute Respiratory Failure and
Overdose
•During Follow -up
•Kidney Infection
•Obstructive Pancreatitis•3 participants reported 4 SAEs
•Within 28 days
•Suicidal Ideation and worsening of
Suicidal Ideation*
•During Follow -up
•Suicidal Ideation*
•Spinal Fracture (post trauma)
18-49 years of age 9-17 years of age
Conclusion
•RIV induced a robust immune response in participants 9 to 17 years and 18 to 49 years
•These findings are consistent with previous research1-5
•Non-Inferiority of HAI immune response induced in those 9 to 17 years of age versus those 18 to 49 years
of age as assessed by GMTs and SC rates at D29 was met for all 4 influenza strains
•The safety profile of the RIV4 vaccine was comparable in both age groups
D, Day; GMT, geometric mean titer; HAI, hemagglutination inhibition; NI, non -inferiority; RIV, recombinant influenza vaccine; SC, seroconversion
References: 1. Hasio A, et al. N Engl J Med. 2023;389:2245 -2255. 2. Zimmerman RK, et al. Vaccine . 2023;41(35):5134 -5140. 3. Dunkle LM et al. N Engl J Med. 2017;376:2427 -2436. 4. Dunkle et al.
Pediatrics .2018;141(5):3021. 5. James C King et al. Vaccine . 2009 Nov 5;27(47):6589 -94.
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Funding
Funding
This study was funded and
sponsored by Sanofi
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Thank you
©Sanofi 2025. All Rights Reserved. MAT-US-2504669 P v2.0 EXP 28 APR 2026
Baseline demographics by age group
9 to 17 years
(N=609)18 to 49 years
(N=606)All
(N=1215)
Sex, n (%)
Male 316 (51.9) 246 (40.6) 562 (46.3)
Female 293 (48.1) 360 (59.4) 653 (53.7)
Age, mean (SD), Year 13.0 (2.48) 34.1 (9.20) 23.5 (12.5)
Racial origin , n (%)
American Indian or Alaska Native 4 (0.7) 0 4 (0 .3)
Asian 1 (0.2) 6 (1.0) 7 (0 .6)
Black or African American 140 (23.0) 90 (14.9) 230 (18.9)
Native Hawaiian or Other Pacific Islander 1 (0.2) 2 (0.3) 3 (0.2)
White 447 (73.4) 493 (81.4) 940 (77.4)
Not Reported 0 2 (0.3) 2 (0.2)
Unknown 1 (0.2) 1 (0.2) 2 (0.2)
Multiple 15 (2.5) 12 (2.0) 27 (2.2)
Ethnicity, n (%)
Hispanic or Latino 107 (17.6) 35 (5.8) 142 (11.7)
Not Hispanic or Latino 494 (81.1) 563 (92.9) 1057 (87.0)
Not reported 7 (1.1) 8 (1.3) 15 (1.2)
Unknown 1 (0.2) 0 1 (<0.1)
n, number of study participants fulfilling the item listed; N, total number of participants included in the study; SD, standa rd deviation
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HAI antibody titers
Ab, antibody; CI, confidence interval; D, day; GMT, geometric mean titer; GMTRs, HAI Ab GMT ratios; HAI, hemagglutination inhibition
•At baseline, the HAI Ab GMTs were higher in participants 9 to 17 years of age than in participants 18 to 49 years of
age for the A/H1N1, A/H3N2, B/Victoria lineage, and were similar in both age groups for B/Yamagata lineage strain
•At D29, the HAI Ab GMTs increased in both age groups and were higher in participants 9 to 17 years of age than in
participants 18 to 49 years of age for all virus strains
HAI Ab GMTs ( 95% CI ) at baseline HAI Ab GMTs ( 95% CI ) at D29
Antigen/ strain 9 to 17 years 18 to 49 years 9 to 17 years 18 to 49 years
A/H1N1 154 (137; 173) 74.9 (65.8; 85.1) 1946 (1795; 2109) 982 (881; 1094)
A/H3N2 111 (95.4; 128) 29.0 (25.7; 32.8) 1975 (1771; 2202) 604 (531; 687)
B/Victoria 48.1 (43.0; 53.8) 37.3 (34.0; 40.9) 405 (362; 452) 258 (233; 285)
B/Yamagata 272 (243; 305) 300 (269; 335) 1941 (1779; 2118) 1593 (1477; 1717)GMTs at baseline and D29 after vaccination of 9 to 17 years vs 18 to 49 years
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Geometric mean of HAI antibody titer
154
111
48.127219461975
4051941
74.9
2937.3300982
604
2581593
110100100010000
A/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean of HAI antibody titer (95% CI)
Influenza strain
D01 (9 to 17 years) D29 (9 to 17 years) D01 (18 to 49 years) D29 (18 to 49 years)
CI, confidence interval; D, day; HAI, hemagglutination inhibition
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Non-inferiority of immune response: GMTs at Day 29
•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for
all 4 ratios of GMTs
9 to 17 years
(N=609)18 to 49 years
(N=606)9 to 17 years / 18 to 49 years
Antigen/
strainM GMT (95% Cl) M GMT (95% Cl) GMT Ratio (95% CI)Non-
inferiority§
A/H1N1 609 1946 (1795; 2109) 606 982 (881; 1094) l.98(1.73;
2.27)Y
A/H3N2 609 1975 (1771; 2202) 606 604 (531; 687) 3.27(2.76;
3.87)Y
B/Victoria 609 405 (362; 452) 606 258 (233; 285) 1.57(1.35;
1.82)Y
B/Yamagata 609 1941 (1779; 2118) 606 1593 (1477; 1717) 1.22(1.09;
1.37)YGMTs at D29 after vaccination of 9 to 17 years vs 18 to 49 years
; §Non-inferiority is concluded if the lower limit of the two -sided 95% CI of the ratio of GMTs between groups (9 to 17 years/18 to 49 years) is > 0.667 for each strain
CI, confidence interval; D, day; GMT, geometric mean titers; M, number of participants with available data for the considered endpoint; N, total number of participants; RIV4, quadrivalent recombinant influenza vaccine
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Individual HAI antibody titer ratios
CI, confidence interval; D, day; GMT, geometric mean titer; GMTRs, HAI Ab GMT ratios; HAI, hemagglutination inhibition •The post -vaccination GMTRs (D29/D01) were similar in both age groups for A/H1N1, A/H3N2, and B/Victoria lineage
strains and were higher in participants 9 to 17 years of age than in participants 18 to 49 years of age for B/Yamagata
lineage strain
GMTRs (95% CI)
Antigen/ strain 9 to 17 years 18 to 49 years
A/H1N1 12.7 (11.1; 14.5) 13.1 (11.4; 15.0)
A/H3N2 17.9 (15.7; 20.3) 20.8 (18.4; 23.6)
B/Victoria 8.41 (7.55; 9.37) 6.91 (6.25; 7.64)
B/Yamagata 7.13 (6.46; 7.87) 5.31 (4.79; 5.88)
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HAI antibody titer ≥40 (1/ dil) and HAI antibody titer ≥10
(1/dil)
CI, confidence interval; D, day; HAI, hemagglutination inhibition•At baseline, the percentages of participants with HAI Ab titer ≥40 (1/ dil) and HAI antibody titer ≥10 (1/ dil) were higher in participants 9 to
17 years of age than in participants 18 to 49 years of age for the A/H1N1 and A/H3N2, and were similar in both age groups for B/Victoria
and B/Yamagata lineage strains
•At D29, the percentages of participants with HAI Ab titer ≥40 (1/ dil) and HAI antibody titer ≥10 (1/ dil) increased for all 4 virus strains and
were high in both age groups
D01 D29
Percentage of
participants with
HAI antibody
titer ≥ 40 (95%
CI)Antigen/
strain9 to 17 years 18 to 49 years 9 to 17 years 18 to 49 years
A/H1N1 87.2 (84.3; 89.7) 71.8 (68.0; 75.3) 99.7 (98.8; 100) 97.5 (96.0; 98.6)
A/H3N2 74.7 (71.1; 78.1) 45.0 (41.0; 49.1) 99.0 (97.9; 99.6) 95.0 (93.0; 96.6)
B/Victoria 61.4 (57.4; 65.3) 59.8 (55.8; 63.8) 95.6 (93.6; 97.1) 97.0 (95.3;98.2)
B/Yamagata 93.1 (90.8; 95.0) 95.2 (93.2; 96.8) 99.5 (98.6; 99.9) 100 (99.4; 100)
Percentage of
participants with
HAI antibody
titer ≥ 10 (95%
CI)A/H1N1 97.0 (95.4; 98.2) 89.8 (87.1; 92.1) 100 (99.4;100) 99.3 (98.3; 99.8)
A/H3N2 89.2 (86.4; 91.5) 77.7 (74.2; 81.0) 100 (99.4; 100) 99.7 (98.8; 100)
B/Victoria 92.1 (89.7; 94.1) 91.7 (89.2; 93.8) 99.5 (98.6; 99.9) 99.8 (99.1; 100)
B/Yamagata 97.9 (96.4; 98.9) 99.5 (98.6;99.9) 100 (99.4; 100) 100 (99.4; 100)
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Seroconversion
SC, seroconversion •The SC rates were similar in both age groups for A/H1N1, A/H3N2, B/Victoria lineage strains and higher in
participants 9 to 17 years of age than in participants 18 to 49 years of age for B/Yamagata lineage strain
SC (% [95% CI])
Antigen/ strain 9 to 17 years 18 to 49 years
A/H1N1 78.3 (74.8; 81.5) 76.4 (72.8; 79.7)
A/H3N2 86.5 (83.6; 89.1) 87.1 (84.2; 89.7)
B/Victoria 76.8 (73.3; 80.1) 73.6 (69.8; 77.0)
B/Yamagata 77.2 (73.6; 80.5) 62.9 (58.9; 66.7)
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Neutralizing Ab titers (SN assay) at D01 and D29 after
vaccination
Ab, antibody; D, day; GMTR, geometric mean titer ratio; HAI, hemagglutination inhibition; SN, seroneutralization •The post -vaccination SN Ab GMTRs were similar in both age groups for A/H1N1, B/Victoria lineage, and B/Yamagata lineage
strains
•It was higher in participants 9 to 17 years of age than in participants 18 to 49 years of age for A/H3N2 strain
614
200
65.84667529
1406
5453733
258
117
34.23204048
564
2402212
1101001000
A/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean
Influenza strain
Pre-dose D01 (9 to 17 years) Post-dose D29 (9 to 17 years) Pre-dose D01 (18 to 49 years) Post-dose D29 (18 to 49 years)
GMTRs (D29/D01) per strain and age group
12.2
(9.4; 15.8)15.5
(11.8; 20.3)7.0
(5.9; 8.3)4.8
(4.1; 5.6)8.3
(6.7; 10.3)7.1
(5.8; 8.6)8.0
(6.5; 9.8)6.8
(5.5; 8.5)
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Summary of geometric mean of HAI antibody titer at
baseline (D01) and D29 by age subgroup
Ab, antibody; CI, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 11 years
(N=186)12 to 17 years
(N=423)18 to 34 years
(N=303)35 to 49 years
(N-303)
Strain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)
A/H1N1 V01 (D01) 186 139 (112; 173) 423 160 (139; 184) 303 102 (85.2; 122) 303 55.0 (46.0; 65.7)
V02 (D29) 186 2101 (1786; 2472) 423 1881 (1717; 2062) 303 1499 (1313; 1711) 303 643 (549; 753)
A/H3N2 V01 (D01) 186 152 (117; 198) 423 96.1 (80.6; 115) 303 27.7 (23.2; 33.0) 303 30.4 (25.6; 36.0)
V02 (D29) 186 2550 (2129; 3055) 423 1765 (1543; 2019) 303 644 (536; 775) 303 567 (473; 679)
B/Victoria V01 (D01) 186 36.3 (30.4; 43.4) 423 54.4 (47.4; 62.6) 303 36.5 (32.0; 41.7) 303 38.1 (33.6; 43.3)
V02 (D29) 186 308 (248; 383) 423 456 (402; 517) 303 270 (232; 315) 303 247 (216; 281)
B/Yamagata V01 (D01) 186 169 (136; 210) 423 336 (296; 381) 303 435 (377; 501) 303 207 (178; 242)
V02 (D29) 186 1339 (1101; 1627) 423 2286 (2094; 2496) 303 2211 (2026; 2414) 303 1147 (1026; 1282)Table 5: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by age subgroup
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Summary of geometric mean of HAI antibody titer at
baseline (D01) and D29 by priming status
CI, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 17 years 18 to 49 years
Previously unvaccinated*
(N-425)Previously vaccinated†
(N=180)Previously unvaccinated*
(N=409)Previously vaccinated†
(N=193)
Strain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)
A/H1N1 V01 (D01) 425 123 (107; 142) 180 255 (208; 313) 409 50.1 (43.2; 58.1) 193 168 (137; 207)
V02 (D29) 425 2276 (2072; 2501) 180 1351 (1169; 1561) 409 1152 (1004; 1322) 193 698 (591; 824)
A/H3N2 V01 (D01) 425 103 (85.5; 123) 180 135 (105; 173) 409 24.7 (21.3; 28.5) 193 39.9 (31.9; 49.7)
V02 (D29) 425 2054 (1804; 2339) 180 1838 (1502; 2250) 409 648 (553; 759) 193 518 (414; 647)
B/Victoria V01 (D01) 425 37.7 (32.9; 43.1) 180 86.7 (72.8; 103) 409 29.8 (26.7; 33.1) 193 59.0 (50.6; 68.7)
V02 (D29) 425 399 (348; 457) 180 422 (348; 512) 409 270 (238; 306) 193 236 (199; 280)
B/Yamagata V01 (D01) 425 215 (187; 247) 180 474 (401; 560) 409 240 (210; 275) 193 478 (406; 564)
V02 (D29) 425 1995 (1785; 2229) 180 1803 (1575; 2064) 409 1784 (1629; 1955) 193 1266 (1113; 1441)Table 17: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by priming status
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Summary of geometric mean of HAI antibody titer at
baseline (D01) and D29 by baseline seropositivity
Ci, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 17 years 18 to 49 years
Baseline seropositive for Baseline seronegative for Baseline seropositive for Baseline seronegative for
Strain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)
A/H1N1 V01 (D01) 591 170 (153; 190) 18 5.00 (NC; NC) 544 102 (90.6; 115) 62 5.00 (NC; NC)
V02 (D29) 591 1989 (1839; 2152) 18 941 (391; 2265) 544 1181 (1071; 1303) 62 193 (123; 305)
A/H3N2 V01 (D01) 543 161 (141; 184) 66 5.00 (NC; NC) 471 48.0 (42.4; 54.4) 135 5.00 (NC; NC)
V02 (D29) 543 2518 (2289; 2770) 66 268 (184; 390) 471 915 (809; 1036) 135 142 (109; 186)
B/Victoria V01 (D01) 561 58.4 (52.5; 65.0) 48 5.00 (NC; NC) 555 44.7 (41.1; 48.6) 50 5.00 (NC; NC)
V02 (D29) 561 471 (424; 524) 48 68.3 (45.1; 103) 555 280 (253; 310) 50 101 (69.0; 149)
B/Yamagata V01 (D01) 596 297 (268; 330) 13 5.00 (NC; NC) 603 306 (275; 341) 3 5.00 (NC; NC)
V02 (D29) 596 2076 (1918; 2248) 13 89.0 (37.3; 212) 603 1596 (1480; 1722) 3 1016 (NC; NC)Table 21: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by baseline seropositivity
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Safety overview
•During the study, 10 participants (0.8%) reported at least 1 SAE and 66 participants (5.1%) reported at least 1 MAAE.
None of the SAEs and MAAEs were considered as related to the vaccine
•No deaths and no AESIs were reported during the study
Safety overview after vaccine injection
9 to 17 years
(N=641)18 to 49 years
(N=658)All
(N=1299)
Period/Participants experiencing
at least one:n/M % (95% Cl) n/M % (95% Cl) n/M % (95% Cl)
Within 28 days after vaccine injection
Unsolicited AR 30/641 4.7 (3.2; 6.6) 26/658 4.0 (2.6; 5.7) 56/1299 4.3 (3.3; 5.6)
AE leading to discontinuation 0/641 0 (0; 0.6) 2/658 0.3 (0; 1.1) 2/1299 0.2 (0; 0.6)
During the study
SAE 3/641 0.5 (0.1; 1.4) 7/658 1.1 (0.4; 2.2) 10/1299 0.8 (0.4; 1.4)
Death 0/641 0 (0; 0.6) 0/658 0 (0; 0.6) 0/1299 0 (0; 0.3)
AESI 0/641 0 (0; 0.6) 0/658 0 (0; 0.6) 0/1299 0 (0; 0.3)
MAAE 29/641 4.5 (3.1; 6.4) 37/658 5.6 (4.0; 7.7) 66/1299 5.1 (4.0; 6.4)
M, number of participants with available data for the relevant endpoint; n, number of participants experiencing the endpoint listed in the first column; N, total number of participants included in
the study
AR, adverse reactions ; AESI, adverse event of special interest; CI, confidence interval; MAAE, medically attended adverse event; SAE, serious adverse event
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