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Safety and Immunogenicity of Moderna COVID -19
Vaccine (2023 -2024 Formula)
Monovalent XBB.1.5 Variant Vaccine
ACIP
September 12, 2023
Frances Priddy, MD MPH
Moderna
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Outline of Presentation
▪Overview of clinical trial of XBB.1.5 vaccine
▪Design
▪Safety data
▪Immunogenicity data
▪Analysis of cross neutralization data for recent variants
▪Summary
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Phase 2/3 Randomized Safety and Immunogenicity Study
of XBB.1.5 -Containing Booster in Adults ≥18 Years
https://clinicaltrials.gov/ct2/show/NCT04927065▪Participants previously received 4 doses of COVID -19 vaccine (primary series and booster of
mRNA -1273 + booster of BA.4/BA.5 vaccine)
▪Focus of today's presentation will be on the monovalent XBB.1.5 vaccine selected for
2023 -2024 season
▪All analyses are descriptive
+Randomized
April 25 -27,
2023
N = 101 50 µg XBB.1.5
25 µg BA.4/5
25 µg XBB.1.5N = 51N = 50
Bivalent
BA.4/5 + XBB.1.5
50 μg Monovalent
XBB.1.5
50 μg
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Demographics and Baseline Characteristics
Study 205J, XBB.1.5 Recipients
CharacteristicMonovalent
XBB.1.5
N = 50
Mean Age – Years 51.6
Median Age – Years (range) 55 (21, 84)
≥ 65 years 11 (22.0%)
% Female 30 (60.0%)
Non-White Race 5 (10.0%)
Months between 2nd and 3rd Dose, median (Q1, Q3) 8.2 (7.8, 9.8)
Months between 3rd and 4th Dose , median (Q1, Q3) 9.8 (8.3, 10.3)
Months between 4th and 5th Dose, median (Q1, Q3) 8.2 (8.1, 8.3)
Prior SARS -CoV-2 Infection 34 (68.0%)5th Dose (3rd Booster)
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Safety of Moderna COVID -19 Vaccine
(2023 -2024 Formula)
XBB.1.5 Monovalent Vaccine
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Within 7 days of injection ; No Grade 4 events reported
Chalkias et al., medRxiv, 2022, Chu et al, Nat Med 28:1041, 2022 Local Reactions Following Booster Doses in Adults
Study 205J and Study 205H, Solicited Safety Set
Participants
(%)68%84% 82%
4% 5% 5%10%5%8%16%20% 21%
0%25%50%75%100%
Mono
XBB.1.5Original Bivalent
BA.4/5Mono
XBB.1.5Original Bivalent
BA.4/5Mono
XBB.1.5Original Bivalent
BA.4/5Mono
XBB.1.5Original Bivalent
BA.4/5Pain Erythema Swelling Axillary Swelling
or TendernessGrade 3 Grade 1 -2Original Vaccine
N = 167Monovalent XBB.1.5
N = 50Bivalent BA.4/BA.5
N = 508
Local reactions similar or lower than previously authorized Moderna COVID -19 vaccines
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Systemic Reactions Following Booster Doses in Adults
Study 205J and Study 205H, Solicited Safety Set
Within 7 days of injection ; No Grade 4 events reported
Chalkias et al., medRxiv, 2022, Chu et al, Nat Med 28:1041, 2022 Grade 3 Grade 1 -2Original Vaccine
N = 167Monovalent XBB.1.5
N = 50Bivalent BA.4/BA.5
N = 508
6% 7%4%34%55%
49%44%59% 60%
38%49%46%
28%41%
35%
8%11%14% 14%35%
22%
0%25%50%75%100%
Participants
(%)
Headache Fatigue Myalgia Arthralgia Nausea /
VomitingChills Fever
≥ 38.0ºC (≥100.4ºF)
Systemic reactions similar or lower than previously authorized Moderna COVID -19 vaccines
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Immunogenicity of Moderna COVID -19
Vaccine (2023 -2024 Formula)
XBB.1.5 Monovalent Vaccine
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Rapid Assessment of Neutralization Capacity of
2023 -2024 XBB.1.5 Vaccine Against Emerging Variants
▪Pre and post booster sera from XBB.1.5 vaccine recipients assessed against
previously dominant and newly emerged variants
▪Duke assay (Lenti -PsVNA) – Day 29 sera assessed
▪Moderna research assay (VSV -PsVNA) – Day 15 sera assessed
▪Titers generally consistent between Day 15 and Day 29
▪Sera tested against:
▪Prior strains: Ancestral (D614G), BA.4/BA.5
▪XBB-lineage: XBB.1.5, XBB.1.16
▪New strains: EG.5.1, FL.1.5.1, BA.2.86
PsVNA – pseudovirus neutralization assay; VSV – vesicular stomatitis virus
Chalkias et al. medRxiv 2023 https://doi.org/10.1101/2023.08.22.23293434
Correlation between Duke and Moderna assay described in Choi et al, Nature Medicine https://doi.org/10.1038/s41591 -021-01527 -y
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155221
7410427113694
1042 1077
110100100010000100000
XBB.1.5 XBB.1.16 EG.5.1 BA.2.86Cross Neutralization Results (Day 29) After XBB.1.5 Vaccine in
Adults – Duke Assay
Study 205J, Per -Protocol Immunogenicity Set - All Participants
Neutralizing
Antibody
Titer (ID50)
14.0-fold riseEG.5.1
16.7-fold riseXBB.1.16Day 29 Pre-Boost
Substantial f old rise demonstrated across newer variants
17.5-fold riseXBB.1.5
Day 29 Pre-Boost
Pseudovirus neutralization assay
10.4-fold riseBA.2.86
Day 29 Pre-Boost Day 29 Pre-Boost Day 29 Pre-Boost
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Cross Neutralization Results (Day 29) After XBB.1.5 Vaccine in
Adults by Baseline SARS -CoV-2 Serostatus - Duke Assay
Study 205J, Per -Protocol Immunogenicity Set
Cross neutralization demonstrated regardless of prior SARS -CoV-2 infection
Pseudovirus neutralization assay82 134
43 6015432246
628 726
1101001000100001000001000000
1 2 3 4
211 27496 1353562 4702
1331 1304
1101001000100001000001000000
1 2 3 4Neutralizing
Antibody
Titer (ID50)
Neutralizing
Antibody
Titer (ID50)
D29 PB
No Prior Infection
Prior Infection
14.6-fold riseEG.5.1
13.9-fold rise
16.7-fold riseXBB.1.16
17.2-fold riseDay 29 Pre-Boost
18.8-fold riseXBB.1.5
16.9-fold rise
13.1-fold riseBA.2.86
9.3-fold rise
D29 PB D29 PB D29 PB
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116144 118931621207 1393 126410571406
110100100010000100000
1 2 3 4 5Cross Neutralization Results (Day 15) After XBB.1.5 Vaccine in
Adults - Moderna Assay
Study 205J, Subset Analysis (N = 20)
Consistent c ross neutralization demonstrated for newer variants, including BA.2.86
Pseudovirus neutralization assay; PB - pre boostNeutralizing
Antibody
Titer (ID50)
D15 PB
10.7-fold riseEG.5.1
8.7-fold riseBA.2.86
11.4-fold riseFL.1.5.1
9.7-fold riseXBB.1.16
10.4-fold riseXBB.1.5
D15 PB D15 PB D15 PB D15 PBDay 15 Pre-Boost
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159 190 142 1322961259 1676 14991157 1600
1101001000100001000001000000
1 2 3 4 585 109 9765 8811581158 1065 964 1237
1101001000100001000001000000
1 2 3 4 5Neutralizing
Antibody
Titer (ID50)
Neutralizing
Antibody
Titer (ID50)
D15 PB
No Prior Infection
Prior InfectionCross Neutralization Results (Day 15) After XBB.1.5 Vaccine in
Adults by Baseline SARS -CoV-2 Serostatus - Moderna Assay
Study 205J, Subset Analysis (N=20)
11-fold riseEG.5.1
10.5-fold rise
14-fold riseBA.2.86
5.4-fold rise
14.8-fold riseFL.1.5.1
8.8-fold rise
10.6-fold riseXBB.1.16
8.8-fold rise
13.6-fold riseXBB.1.5
7.9-fold rise
D15 PB D15 PB D15 PB D15 PB
Cross neutralization demonstrated regardless of prior SARS -CoV-2 infectionDay 15 Pre-Boost
Pseudovirus neutralization assay
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1151
123
162417139961
3355
298468
276148
110100100010000100000
1 2 3 4 5 6Cross Neutralization Results (Day 29) in Adults after Bivalent
BA.4/BA.5 Vaccine
Study 205H – Duke Assay
Neutralizing
Antibody
Titer (ID50)Day 29 Pre-Boost
Ancestral
8.7-fold riseBA.4/BA.5
27.3-fold riseXBB.1.5
12.3-fold riseXBB.2.3.2
15.8-fold riseEG.5
11.6- fold riseXBB.1.16
19.3-fold rise
D29 PB
Limited cross neutralization to newer variants after previously authorized BA.4/BA.5 bivalent vaccineD29 PB D29 PB D29 PB D29 PB D29 PB
Pseudovirus neutralization assay; PB - pre boost
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Summary
Safety and Immunogenicity of Moderna COVID -19 Vaccine (2023 -2024 Formula)
XBB.1.5 Vaccine
Moderna’s
Vaccine
PreparednessClinical Study
of XBB.1.5
Vaccine
▪Moderna will supply an XBB.1.5 vaccine for Fall 2023
▪Moderna will continue its ongoing variant monitoring and risk
assessment of emerging variants▪Safety profile of XBB.1.5 vaccine consistent with previously authorized
vaccines
▪Robust neutralizing antibody titers against XBB.1.5, XBB.1.16, EG.5.1,
FL.1.5.1, and BA.2.86 measured in sera from recipients of XBB.1.5
vaccine
▪XBB.1.5 vaccine is anticipated to be effective against current
SARS -CoV-2 variants
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THANK YOU to Our Study Collaborators,
Investigators, and Participants
▪All investigators
▪Study site personnel
▪Laboratory personnel
▪Most importantly, the individuals who participated in these trials