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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.1.5

N = 51

N = 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

Characteristic

Monovalent

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%)

5

th 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.1.5

Original Bivalent

BA.4/5

Mono

XBB.1.5

Original Bivalent

BA.4/5

Mono

XBB.1.5

Original Bivalent

BA.4/5

Mono

XBB.1.5

Original Bivalent

BA.4/5

Pain Erythema Swelling Axillary Swelling 

or Tenderness

Grade 1-2 Grade 3

Original Vaccine

N = 167

Monovalent XBB.1.5

N = 50

Bivalent 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 1-2 Grade 3

Original Vaccine

N = 167

Monovalent XBB.1.5

N = 50

Bivalent 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 / 

Vomiting

Fever Chills

≥ 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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155 221

74 104

2711 3694

1042 1077

1

10

100

1000

10000

100000

XBB.1.5 XBB.1.16 EG.5.1 BA.2.86

Cross 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 rise

EG.5.1

16.7-fold rise

XBB.1.16

Pre-Boost Day 29

Substantial fold rise demonstrated across newer variants

17.5-fold rise

XBB.1.5

Pre-Boost Day 29

Pseudovirus neutralization assay

10.4-fold rise

BA.2.86

Pre-Boost Day 29 Pre-Boost Day 29 Pre-Boost Day 29
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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 assay

82 134

43 60

1543 2246

628 726

1

10

100

1000

10000

100000

1000000

1 2 3 4

211 274 96 135

3562 4702

1331 1304

1

10

100

1000

10000

100000

1000000

1 2 3 4

Neutralizing 

Antibody 

Titer (ID50)

Neutralizing 

Antibody 

Titer (ID50)

PB D29

No Prior Infection

Prior Infection

14.6-fold rise

EG.5.1

13.9-fold rise

16.7-fold rise

XBB.1.16

17.2-fold rise

Pre-Boost Day 29

18.8-fold rise

XBB.1.5

16.9-fold rise

13.1-fold rise

BA.2.86

9.3-fold rise

PB D29 PB D29 PB D29
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116 144 118 93

162

1207 1393 1264 1057

1406

1

10

100

1000

10000

100000

1 2 3 4 5

Cross Neutralization Results (Day 15) After XBB.1.5 Vaccine in 

Adults - Moderna Assay

Study 205J, Subset Analysis (N = 20)

Consistent cross neutralization demonstrated for newer variants, including BA.2.86

Pseudovirus neutralization assay; PB - pre boost

Neutralizing 

Antibody 

Titer (ID50)

PB D15

10.7-fold rise

EG.5.1

8.7-fold rise

BA.2.86

11.4-fold rise

FL.1.5.1

9.7-fold rise

XBB.1.16

10.4-fold rise

XBB.1.5

PB D15 PB D15 PB D15 PB D15

Pre-Boost Day 15
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159 190 142 132 296

1259 1676 1499 1157 1600

1

10

100

1000

10000

100000

1000000

1 2 3 4 5

85 109 97 65 88

1158 1158 1065 964 1237

1

10

100

1000

10000

100000

1000000

1 2 3 4 5

Neutralizing 

Antibody 

Titer (ID50)

Neutralizing 

Antibody 

Titer (ID50)

PB D15

No Prior Infection

Prior Infection

Cross 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 rise

EG.5.1

10.5-fold rise

14-fold rise

BA.2.86

5.4-fold rise

14.8-fold rise

FL.1.5.1

8.8-fold rise

10.6-fold rise

XBB.1.16

8.8-fold rise

13.6-fold rise

XBB.1.5

7.9-fold rise

PB D15 PB D15 PB D15 PB D15

Cross neutralization demonstrated regardless of prior SARS-CoV-2 infection

Pre-Boost Day 15

Pseudovirus neutralization assay
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1151

123

16 24 17 13

9961

3355

298

468

276 148

1

10

100

1000

10000

100000

1 2 3 4 5 6

Cross Neutralization Results (Day 29) in Adults after Bivalent 

BA.4/BA.5 Vaccine 

Study 205H – Duke Assay

Neutralizing 

Antibody 

Titer (ID50)

Pre-Boost Day 29

Ancestral 

8.7-fold rise

BA.4/BA.5

27.3-fold rise

XBB.1.5

12.3-fold rise

XBB.2.3.2

15.8-fold rise

EG.5

11.6- fold rise

XBB.1.16

19.3-fold rise

PB D29

Limited cross neutralization to newer variants after previously authorized BA.4/BA.5 bivalent vaccine

PB D29 PB D29 PB D29 PB D29 PB D29

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 

Preparedness

Clinical 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