Slide 1

Safety and Immunogenicity of 

a 50 μg Booster Dose of Moderna COVID-19 Vaccine

Jacqueline Miller, MD, FAAP

ACIP

Oct 21, 2021
Slide 2

• A single Moderna COVID-19 Vaccine booster dose (0.25 mL) may be administered 

intramuscularly at least 6 months after completing a primary series of the Moderna 

COVID-19 Vaccine to individuals:

̶ 65 years of age and older 

̶ 18 through 64 years of age at high risk of severe COVID-19

̶ 18 through 64 years of age with frequent institutional or occupational exposure

to SARS-CoV-2 

• A single booster dose of the Moderna COVID-19 Vaccine (0.25 mL) may be 

administered as a heterologous booster dose following completion of primary 

vaccination with another authorized or approved COVID-19 vaccine. The eligible 

population(s) and dosing interval for the heterologous booster dose are the same 

as those authorized for a booster dose of the vaccine used for primary vaccination.

EUA for Use of Moderna COVID-19 Vaccine as a Booster

FDA authorized, Oct 20, 2021
Slide 3

Moderna COVID-19 Vaccine

Vaccination Schedule under EUA

Dose 1 

100 μg 

(0.5 mL)

Dose 2 

100 μg 

(0.5 mL)

Individuals

≥ 18 Years

Booster

50 μg 

(0.25 mL)

Dose 3

100 μg

(0.5 mL)

Dose 1 

100 μg 

(0.5 mL)

Dose 2 

100 μg 

(0.5 mL)

Immunocompromised

≥ 18 Years

4 Weeks ≥ 1 Month ≥ 6 Months Post Dose 2
Slide 4

Use of Moderna COVID-19 Vaccine in US 

Since December 2020 EUA

1,650,586

69,603,147

193,178,840

Received

Third Dose

Fully

Vaccinated

Doses

Distributed

Adapted from CDC COVID Data Tracker (as of October 20, 2021)
Slide 5

Update on 

mRNA-1273 

Efficacy through 

End of Blinded 

Phase

Phase 3 Study 301
Slide 6

mRNA-1273 Vaccine Efficacy to Prevent COVID-19 Disease was 93.2% 

through 5.3 Months of Follow-up

Per Protocol Set

0

1

2

3

4

5

6

7

8

9

Time from Randomization (days)

Placebo

mRNA-1273

0 20 40 60 80 100 120 140 160 180 200 220 240 260

Cumulative 

Event Rate

%

Median 5.3 months 

of follow-up

El Sahly, NEJM, 2021
Slide 7

Time from Randomization (days)

mRNA-1273 Vaccine Efficacy to Prevent Severe COVID-19 Disease was 98.2% 

through 5.3 Months of Follow-up

Per Protocol Set

Placebo

mRNA-1273

0.0

0.5

1.0

1.5

2.0

0 20 40 60 80 100 120 140 160 180 200 220 240 260

Cumulative 

Severe Event 

Rate, %

Median 5.3 months 

of follow-up

El Sahly, NEJM, 2021
Slide 8

Exploratory 

Analysis of 

Antibody 

Persistence and 

Boosting

Study 201B
Slide 9

Exploratory Analysis Against Variants of Concern 

Study 201B 50 μg Booster after 100 μg Primary Series (N=11-20)

GMT

23 to 44-Fold Increase After Booster

0

1

2

3

4

5

WT

1,210 84 188

BetaGamma

Month 1

Post-Dose 2

WT

198 27 30 30

BetaGammaDelta

Month 6-8

Post-Dose 2

4,588 864 1,308 1,268

WT Beta GammaDelta

Day 14

Post-Booster

NAb Titer 

(ID50)

Lower Limit of 

Quantification

N= 20 20 20 20 20 20 11 20 20 20 11 1

10

100

1,000

10,000

WT: original strain (D614G)

Research VSV pseudoneutralization assay used; Adapted from Choi et al., Nature Medicine 2021
Slide 10

COVID-19 

Disease in 

Vaccinated 

Individuals from 

July to August, 

2021

Phase 3 Study 301
Slide 11

COVID-19 Cases by Month in Vaccinated Subjects 

Study 301

Initial 

Randomization

EUA and Cross-over

Per Protocol Cases of 

COVID-19

Early Vaccination mRNA-1273

Placebo

4

15 22 23

3

15 22

8 9

81

169

0

50

100

150

200

Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug

2020 2021

Aug Sept Oct Nov Dec Jan Feb Mar Apr May Jun July Aug

Increase in 

COVID-19 

Cases

Later Vaccination

(open-label cross over)

mITT Population
Slide 12

Incidence Rates of COVID-19 in Early and Later Vaccinated Groups, 

July – August 2021

Study 301

Median follow-up from 1st dose; Analysis of breakthrough cases observed from July 1 to August 27, 2021, mITT population

Baden et al., MedRxiv, 2021

COVID-19

Cases /

1000 Person

Years

77.1

87.3

49.0 47.8 52.8

39.5

0

10

20

30

40

50

60

70

80

90

100

All 18 - 64 ≥ 65

n=162 n=88 n=136 n=68 n=26 n=20

36.4%

(95% CI 17.1-51.5)

39.6%

(95% CI 18.6-55.5)

17.4%

(95% CI -53.9-56.3)

Later (8-month median follow-up)

Early (13-month median follow-up)

Incidence rates were higher in the group vaccinated earlier

All 18 - 64 years ≥ 65 years

Person years 2,102 1,796 1,558 1,289 544 507
Slide 13

50 μg Booster of 

mRNA-1273

in Previously 

Vaccinated 

Individuals

Study 201B
Slide 14

• Goal was to use optimal effective dose for boosting

• Lower booster doses than those used for primary series of other vaccines shown

to reactivate immune memory

• Lower booster dose increases worldwide vaccine supply of mRNA-1273

Rationale for Booster Dose Selection
Slide 15

Study N

Previous Dose of mRNA-1273

Booster

Dose

Interval between 

Dose 2 & 

Doses 1 & 2 Booster Dose

201B 

(boost with 

mRNA-1273)

146 50 μg 50 μg

≥ 6 months

149 100 μg 50 μg

301 

Immunogenicity 

Subset

1,055 100 μg 

(primary series only) None -

Vaccine Effectiveness of 50 μg Booster Dose Inferred by 

Immunobridging to Study 301

Per protocol set 
Slide 16

50 μg Booster After 

100 μg Primary Series

N = 171

50 μg Booster 

Pooled

N = 344

Age

Mean (years) 52 52

18-64 78% 76%

≥ 65 22% 24%

Sex Female 61% 66%

Race

White 96% 95%

Black or African American 3% 2%

Asian < 1% < 1%

American Indian or Alaska Native < 1% < 1%

Ethnicity

Hispanic or Latino 6% 6%

Not Hispanic or Latino 94% 94%

Demographic Characteristics 

Study 201B Safety Set
Slide 17

Safety Data for 

50 μg Booster 

After 

100 μg Primary 

Series

Study 201B
Slide 18

Follow-up Period for Safety Data Collection

Median 5.7 Months Safety Follow-up

Booster

Dose Active Surveillance

7 Days

28 Days

End of 

Study SAEs, MAAEs, Deaths, and AEs Leading to Discontinuations

Solicited 

Adverse 

Reactions

Unsolicited AEs
Slide 19

No Grade 4 solicited local adverse reactions were reported

Solicited safety set 

Solicited Local Adverse Reactions within 7 Days

Study 201B 50 μg Booster Dose After 100 μg Primary Series vs Study 301

0%

20%

40%

60%

80%

100%

50 μg

Booster

Study

301

50 μg

Booster

Study

301

50 μg

Booster

Study

301

50 μg

Booster

Study

301

Pain Erythema Swelling Axillary Swelling 

or Tenderness

N = 167 14,688 167 14,687 167 14,687 167 14,687

Local reactions were generally similar for booster dose and Dose 2 of primary series 

88%

84%

9% 5%

12%

5%

14%

20%

Grade 1 Grade 2 Grade 3
Slide 20

Grade 4 fever & nausea/vomiting occurred in < 0.1% of subjects in Study 301. 

No Grade 4 solicited systemic adverse reactions reported in Study 201B.

Solicited safety set 

Solicited Systemic Adverse Reactions within 7 Days

Study 201B 50 μg Booster Dose After 100 μg Primary Series vs Study 301

Nausea /

Vomiting

0%

20%

40%

60%

80%

100%

50 ug

Booster

Study

301

50 ug

Booster

Study

301

50 ug

Booster

Study

301

50 ug

Booster

Study

301

50 ug

Booster

Study

301

50 ug

Booster

Study

301

50 ug

Booster

Study

301

N = 166 14,682 167 14,687 167 14,687 167 14,687 167 14,687 167 14,687 167 14,687

16%

7%

59% 55%

65%

59% 58%

49%

41%

19%

11%

44%

35%

43%

Systemic reactions were generally similar after booster dose compared to Dose 2 of primary series

Fever Headache Fatigue Myalgia Arthralgia Chills

Grade 1 Grade 2 Grade 3 Grade 4
Slide 21

Unsolicited Adverse Events

Study 201B 50 μg Booster Dose vs Study 301

As of August 16, 2021 (median 5.7 months safety follow-up)

No vaccine-related SAEs or deaths in Study 201B to date

Participants Reporting at Least One Event, n (%)

50 μg Booster After 

100 μg Primary Series

N = 171

50 μg Booster 

Pooled

N = 344

Study 301

N = 15,184

Medically attended AEs (MAAE) 41 (24%) 78 (23%) 3,468 (23%)

Vaccine-related MAAE 2 (1%) 2 (< 1%) 213 (1%)

Serious adverse events 2 (1%) 4 (1%) 268 (2%)

Vaccine-related SAE 0 0 12 (< 0.1%)

Deaths 0 0 17 (0.1%)

Adverse event leading to study 

discontinuation 0 0 26 (0.2%)
Slide 22

Immunogenicity 

of 50 μg Booster 

Dose – Original 

Strain and Delta 

Variant

Study 201B
Slide 23 Per protocol set 

Geometric Mean Titer (95% CI)

Post Booster / Post Dose 2 

GMR

(95% CI)

28 days Post Booster 

Study 201B Pooled

N = 295

28 days Post Dose 2 

Study 301

N = 1,053

1,768

(1,586, 1,970)

1,033

(974, 1,095)

1.7

(1.5, 1.9)

Geometric Mean Ratio (GMR) of Neutralization Titers (Pre-specified Hypothesis)

Study 201B (Pooled) vs Study 301

First co-primary endpoint of GMR non-inferiority margin of 1.5 and point estimate of ≥ 1.0 met
Slide 24

Geometric Mean Titer (95% CI)

Post Booster / Post Dose 2 

GMR 

(95% CI)

28 days Post 50 μg Booster 

after 100 μg Primary Series

Study 201B 

N = 149

28 days Post Dose 2 

Study 301 

N = 1,053

1,802

(1,548, 2,099)

1,027

(968, 1,089)

1.8

(1.5, 2.1)

Geometric Mean Ratio (GMR) of Neutralization Titers 

Study 201B 50 μg Booster Dose After 100 μg Primary Series vs Study 301 

Co-primary endpoint of GMR non-inferiority margin of 1.5 and point estimate of ≥ 1.0 

also met for 100 μg Primary Series followed by 50 μg Booster

Per protocol set

Measured as pseudovirus neutralization ID50 
Slide 25 Per protocol set 

Study 201B

50 μg Booster Pooled

N = 294

Study 301

100 μg Primary Series

N = 1,050

Baseline Geometric Mean Titer (GMT) 126 10

GMT 28 days post dose 1,893 1,081

Participants achieving seroresponse, n (%) 275 (94%) 1,038 (99%)

95% CI 90.1, 96.1 98.0, 99.4

Difference in seroresponse rate (SRR) -5.3

95% CI -8.8, -2.9 

Seroresponse Rates based on 3.3-Fold Definition (Prespecified Hypothesis) 

Study 201B (Pooled) vs Study 301

Co-primary endpoint of SRR met (lower bound of 95% CI ≥ -10%)
Slide 26 Per protocol set 

Seroresponse Rates Based on 4-Fold Rise from Pre-Booster Titers

Study 201B 50 μg Booster after 100 μg Primary Series vs Study 301

SRR success criteria not met (lower bound of 95% CI ≥ -10%)

50 μg Booster After 

100 μg Primary Series

N = 149

Study 301

100 μg Primary Series

N = 1,050

Baseline Geometric Mean Titer (GMT) 150 10

GMT 28 days post dose 1,952 1,081

Participants achieving seroresponse, n (%) 131 (88%) 1,033 (98%)

95% CI 81.6, 92.7 97.4, 99.1

Difference in seroresponse rate (SRR) -10.5

95% CI -16.7, -6.1
Slide 27 Per protocol set 

Neutralizing Antibody Titer Comparison for Subjects Who Had ≥ 4-Fold 

Rise vs < 4-Fold Rise to Original Strain D614G after Booster Dose

Study 201B (Pooled)

108

492

1,964 1,354

1

10

100

1,000

10,000

>=4-fold <4-fold

< 4-Fold Rise

N = 29

≥ 4-Fold Rise

N = 265

Subjects who did not meet 4-fold rise had 4 times higher pre-booster titers 

compared to those who did meet 4-fold rise

Pre-Booster 28 Days After 

Boost Dose

Pre-Booster 28 Days After 

Boost Dose

ID50

Titer
Slide 28

Per protocol set

GMFR = Geometric Mean Fold Rise 

Geometric Mean Fold Rise of Neutralization Titers Against Original 

Strain D614G by Age and Overall

Study 201B 50 μg Booster after 100 μg Primary Series

177

91

150

2,070 1,634 1,952

1

10

100

1,000

10,000

18-65 >=65 overall

18-64 years

N = 112

GMFR = 11.7

≥ 65 years

N = 37

GMFR = 17.9

Overall

N = 149

GMFR = 13.0

Older adults, who are at greater risk of complications of COVID-19, 

achieve a 17.9-fold GMFR to Wuhan-1 D614G

ID50

Titer

Pre-Booster 28 Days After 

Boost Dose

Pre-Booster 28 Days After 

Boost Dose

Pre-Booster 28 Days After 

Boost Dose
Slide 29

55

32

48

872 706 828

1

10

100

1,000

18-65 >=65 overall

18-64 years

N = 112

GMFR = 15.9

≥ 65 years

N = 37

GMFR = 22.2

Overall

N = 149

GMFR = 17.3

Geometric Mean Fold Rise of Neutralization Titers Against the Delta 

Variant by Age and Overall

Study 201B 50 μg Booster after 100 μg Primary Series

15.9 to 22.2-fold increase in post-boost titers against Delta was achieved in both age groups

ID50

Titer

GMFR = Geometric Mean Fold Rise

Pre-Booster 28 Days After 

Boost Dose

Pre-Booster 28 Days After 

Boost Dose

Pre-Booster 28 Days After 

Boost Dose
Slide 30

Summary
Slide 31

• Rates of adverse reactions (ARs) with 50 μg booster dose comparable to those 

observed after Dose 2 of primary series

̶Pain at injection site most common solicited local AR in both groups

̶Headache, fatigue and myalgia most common systemic ARs in both groups

̶Majority of ARs were mild-to-moderate in severity

̶Axillary swelling or tenderness was the only AR more frequently reported after 

booster dose as compared to dose 2 in Study 301

• No vaccine-related SAEs or deaths in Study 201B

Safety Summary - 50 μg Booster Dose
Slide 32

• Pre-specified co-primary hypotheses (GMR & SRR difference) were met on pooled 

dataset

• 50 μg booster dose following 100 μg primary series results in 

̶Higher antibody responses to original virus (D614G) than post- dose 2 in

Study 301 (GMR = 1.8)

̶13-fold rise from pre-booster titers for original virus

̶17-fold rise from pre-booster titers for Delta variant

• Consistently high antibody titers in both age groups (18-64 and ≥ 65 year olds)

Immunogenicity Summary - 50 μg Booster Dose

GMR = geometric mean ratio

SRR = seroresponse rate
33 Confidential and Proprietary

THANK YOU! 

NIH/COV-PN

All investigators at many study sites

Study site personnel

BARDA

Montefiori laboratory at Duke University

Most importantly, the many individuals who 

participated in these trials

33