Senior Fellow Division of Infectious Diseases University of Washington Last Updated January 31 2021 David H Spach MD Professor of Medicine Division of Infectious Diseases University of Washington ID: 932615
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Slide1
COVID-19 mRNA Vaccines
Sarah McGuffin, MDSenior FellowDivision of Infectious DiseasesUniversity of Washington
Last Updated: January 31, 2021
David H. Spach, MDProfessor of MedicineDivision of Infectious DiseasesUniversity of Washington
mRNA-1273 and BNT162b2: Phase 3 Data
Slide2Safety and Efficacy of BNT162b2 mRNA Covid-19 Vaccine
Published Data
—Placebo-controlled, observer-blinded trial
Source: Polack FP, et al. N
Engl
J Med. 2020;383:2603-15.
Slide3Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
BackgroundSource: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
BNT162b2 is a lipid nanoparticle– formulated nucleoside-modified RNA encoding the SARS-CoV-2 full-length spike protein, modified by two proline mutations to lock the protein in the prefusion conformation.
Slide4Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Study DesignSource: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Study Design
Background
: Phase 2/3
multinational, placebo-controlled, observer-blinded, BNT162b2 COVID-19 vaccine safety and efficacy trial conducted between July 27, 2020 and November 14, 2020
Location:
Global (United States, Argentina, Brazil, South Africa, Germany, Turkey)
Inclusion
Criteria (n = 43,448)
- Age ≥
16 years
- Healthy or with stable chronic medical conditions
Exclusion
Criteria
-
History of Covid-19 infection
- Treatment with immunosuppressive therapy, diagnosis of immunocompromising condition
Primary Endpoints
-
E
fficacy against confirmed Covid-19 at least 7 days after the second dose
- Solicited local or systemic adverse effects within 7 days of vaccination
- Unsolicited adverse events through 1 months after the second dose
- Unsolicited serious adverse events through 6 months after the second dose
Slide5Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Study Design
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
BNT162b2 30
μg
(0.3 mL volume per dose), 2 IM doses, 21 days apart
Saline placebo, 2 IM doses, 21 days apart
or
Study Participant Groups
Slide6Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Baseline Characteristics: Gender Distribution for ALL Participants
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Slide7Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Baseline Characteristics: Age Distribution for ALL Participants
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Slide8Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Baseline Characteristics, by Study Group
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Baseline Characteristics
BNT162b2
(N=18,860)
Placebo
(N=18,846)
Male, n (%)
9,639 (51.1)
9,436 (50.1)
Female, n (%)
9,221 (48.9)
9,410 (49.9)
Race or ethnic group — no. (%)†
White
15,636 (82.9)
15,630 (82.9)
Black or African American
1,729 (9.2)
1,763 (9.4)
Asian
801 (4.2)
807 (4.3)
Native American or Alaska Native
102 (0.5)
99 (0.5)
Native Hawaiian or other Pacific Islander
50 (0.3)
26 (0.1)
Multiracial449 (2.4)406 (2.2) Not reported93 (0.5)115 (0.6)Hispanic or Latinx5,266 (27.9)5,277 (28.0)Country— no. (%)Argentina2,883 (15.3)2,881 (15.3)Brazil1,145 (6.1)1,139 (6.0)South Africa372 (2.0)372 (2.0) United States14,460 (76.6)14,454 (76.7)
† Race or ethnic group was reported by the participants.
Slide9Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Baseline Characteristics, by Study Group
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Baseline Characteristics
BNT162b2
(N=18,860)
Placebo
(N=18,846)
Age group — no. (%)
16–55 years
10,889 (57.7)
10,896 (57.8)
>55 years
7,971 (42.3)
7,950 (42.2)
Age at vaccination — years
Median
52.0
52.0
Range
16–89
16–91
Body-mass index (BMI)
≥30.0: obese
6,556 (34.8)
6,662 (35.3)
Slide10Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Outcomes Efficacy against Covid-19 ≥7 days after Second Dose*Source: Polack FP, et al. N
Engl J Med. 2020;383:2603-15.
Efficacy End Point
BNT162b2
Placebo
Vaccine Efficacy, % (95% Credible Interval)‡
No. of Cases
Surveillance Time (n)†
No. of Cases
Surveillance Time (n)†
(N=18,198)
(N=18,325)
Covid-19 occurrence ≥7 days after second dose in participants without evidence of existing or prior SARS-CoV-2 infection
8
2.214 (17,411)
162
2.222 (17,511)
95.0 (90.3–97.6)
(N=19,965)
(N=20,172)
Covid-19 occurrence ≥7 days after second dose in participants with and those without evidence of prior SARS-CoV-2 infection
9
2.332 (18,559)
169
2.345 (18,708)
94.6 (89.9–97.3)
* The total population was 40,137. The total population without evidence of baseline infection was 36,523
† The surveillance time is the total time in 1,000 person-years for the given end point across all participants within each group at risk for the end point.
‡ Calculated with the use of a beta-binomial model with prior beta (0.700102, 1) adjusted for the surveillance time.
Slide11Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Vaccine Efficacy Overall and by SubgroupsSource: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Efficacy End Point Subgroup
BNT162b2
(N=18,198)
Placebo
(N=18,325)
Vaccine Efficacy, %
(95% CI)†
No. of Cases
Surveillance time (No. at Risk)*
No. of Cases
Surveillance time (No. at Risk)*
Overall
8
2.214 (17,411)
162
2.222 (17,511)
95.0 (90.0–97.9)
Age group
16 to 55 years
5
1.234 (9,897)
114
1.239 (9,955)
95.6 (89.4–98.6)
>55 years
3
0.980 (7,500)
48
0.983 (7,543)93.7 (80.6–98.8)≥65 years10.508 (3,848) 190.511 (3,880)94.7 (66.7–99.9)≥75 years00.102 (774) 50.106 (785)100.0 (−13.1–100.0) SexMale31.124 (8,875)811.108 (8762)96.4 (88.9–99.3)
Female51.090 (8,536) 811.114 (8,749)93.7 (84.7–98.0)* The surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. † The confidence interval (CI) for vaccine efficacy is derived according to the Clopper–Pearson method, adjusted for surveillance time.
Slide12Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Participants with Covid-19 After Second Dose*Covid-19 at Least 7 Days after Second Dose of BNT162b Vaccine or Placebo
Source: Polack FP, et al. N Engl
J Med. 2020;383:2603-15.
Vaccine Efficacy 95.0%
*Participants who had no evidence of existing or prior SARS-CoV-2 infection.
Slide13Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Participants with Covid-19 After First DoseCovid-19 After First Dose of BNT162b Vaccine or Placebo
Source: Polack FP, et al. N Engl
J Med. 2020;383:2603-15.
Slide14Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Vaccine Efficacy by Age GroupsSource: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Slide15Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Covid-19 During Study, Modified Intention-to-Treat Analysis
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Slide16Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Vaccine Efficacy Throughout Study, Modified-Intention-to-Treat Analysis
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Slide17Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Local and Systemic Reactions Reported with 7 Days of Injection
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Event
BNT162b2
Placebo
BNT162b2
Placebo
Age 16-55 years
Age 16-55 years
Age > 55 years
Age > 55 years
Pain at injection site <7 days
After first dose
83%
14%
71%
9%
After second dose
78%
12%
66%
8%
Fatigue
After first dose
47%
33%
34%
23%
After second dose
59%23%51%17%HeadacheAfter first dose42%34%25%18%After second dose52%24%39%14%Fever (≥38°C)After first dose4%1%1%0%After second dose16%0%11%0%Use of antipyretic or analgesic
After first dose28%14%20%
12%
After second dose
45%
13%
38%
10%
Slide18Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Results: Adverse Events
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Adverse Event
BNT162b2
(N
a
=21621)
Placebo
(
N
b
=21631)
N
b
(%)
N
b
(%)
Any Event
5770 (26.7)
2638 (12.2)
Related
c
4484 (20.7)
1095 (5.1)
Severe
240 (1.1)
139 (0.6)Life-threatening21 (0.1) 24 (0.1)Any serious adverse event126 (0.6)111 (0.5)Relatedc4 (0.0) 0Severe71 (0.3) 68 (0.3)Life-threatening21 (0.1) 23 (0.1)Any adverse event leading to withdrawal37 (0.2)30 (0.1)Relatedc16 (0.1) 9 (0.0)Severe13 (0.1)9 (0.0)Life-threatening3 (0.0)6 (0.0)Death2 (0.0)4 (0.0)aN
= number of participants in the specified group. This value is the denominator for the percentage calculations. bN = number of participants reporting ≥1 occurrence of the specified event category. For ‘any event’, n = the number of participants reporting ≥1 occurrence of any event. c Assessed by the investigator as related to investigational product.
Slide19Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Outcomes Vaccine Efficacy Overall and by SubgroupSource: Polack FP, et al. N
Engl J Med. 2020;383:2603-15.
Efficacy End Point Subgroup
BNT162b2
(N=18,198)
Placebo
(N=18,325)
Vaccine Efficacy, % (95% CI)†
No. of Cases
Surveillance time (No. at Risk)*
No. of Cases
Surveillance time (No. at Risk)*
Race or ethnic group‡
White
7
1.889 (14,504)
146
1.903 (14,670)
95.2 (89.8–98.1)
Black or African American
0
0.165 (1,502)
7
0.164 (1,486)
100.0 (31.2–100.0)
All others
1
0.160 (1,405)
9
0.155 (1,355)89.3 (22.6–99.8)Hispanic or Latinx30.605 (4,764) 530.600 (4,746)94.4 (82.7–98.9) Non-Hispanic, non-Latinx51.596 (12,548)1091.608 (12,66195.4 (88.9–98.5)Country
Argentina10.351 (2,545)350.346 (2,52197.2 (83.3–99.9)Brazil
1
0.119 (1,129
8
0.117 (1,121)
87.7 (8.1–99.7)
United States
6
1.732 (13,359)
119
1.747 (13,506)
94.9 (88.6–98.2)
* The surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point.
† The confidence interval (CI) for vaccine efficacy is derived according to the Clopper–Pearson method, adjusted for surveillance time.
‡ Race or ethnic group was reported by the participants. “All others” included the following categories: American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, multiracial, and not reported.
Slide20Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Additional notes
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
The cumulative incidence of Covid-19 cases over time among placebo and vaccine recipients begins to diverge by 12 days after the first dose, 7 days after the estimated median viral incubation period of 5 daysIn the interval between the first and second doses, the observed vaccine efficacy against Covid-19 was 52%
Some protection occurs as soon as 12 days after first dose
Of the 10 cases of severe Covid-19 disease, only 1 was in vaccine group
Provides preliminary evidence of vaccine-mediated protection against severe disease
Provides preliminary evidence to alleviate concerns over vaccine-mediated disease enhancement
Slide21Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Study Limitations
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Median follow-up time of 2 months after the second dose limits probability of detecting less common adverse events reliablyAssessment of long-term vaccine safety and efficacy cannot be conducted in the context of maintaining a placebo group for the planned follow-up period of 2 years after the second doseStudy did not address whether vaccine prevents:
Asymptomatic Covid-19 infection
Covid-19 in younger adolescents, children, pregnant women, and immunocompromised individuals
Slide22Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Authors’ Conclusions
Source: Polack FP, et al. N Engl J Med. 2020;383:2603-15.
Conclusions
: “
A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines.
”
Slide23Efficacy and Safety of mRNA-1273 SARS-CoV-2 Vaccine
COVE Study
Published Data
—Randomized, placebo-controlled, observer-blinded trial
Source: Baden LR, et al. N
Engl
J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Slide24Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
BackgroundSource: Baden LR, et al. N Engl J Med. 2020 Dec
30. DOI: 10.1056/NEJMoa2035389
mRNA-1273 is a lipid-nanoparticle (LNP)-encapsulated mRNA vaccine expressing the prefusion-stabilized spike glycoprotein
Slide25Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Study DesignSource: Baden LR, et al. N Engl
J Med. 2020 Dec 30. DOI: 10.1056/NEJMoa2035389
Study Design
Background
: Phase 3
randomized, placebo-controlled, observer-blinded, mRNA-1273 COVID-19 vaccine safety and efficacy trial between July 27 and October 23, 2020 in the United States
Inclusion
Criteria (n = 30,420)
- Age ≥18
years
- At
locations or circumstances putting the participant at an appreciable risk of SARS-CoV-2
infection and/or high risk of severe Covid-19
Exclusion
Criteria
-
Known history of SARS-CoV-2 infection
-
Pregnant or breastfeeding
-
Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections
Primary Endpoints
-
Solicited and unsolicited local and systemic adverse events
- Prevention of symptomatic Covid-19 at least 14 days after the second injection
Secondary Endpoints
- Prevention of severe Covid-19
- Efficacy of vaccine at preventing Covid-19 after a single dose
Follow-up Time period:
median follow-up duration ≥2 months after completing two-dose regimen
Slide26Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Study DesignSource: Baden LR, et al. N Engl
J Med. 2020 Dec 30. DOI: 10.1056/NEJMoa2035389
Risk factors for Severe Covid-19 Illness
Participants who were younger than 65 years of age were categorized as at risk for severe Covid-19 illness if they had at least one of the following:
Chronic lung disease or moderate to severe asthma
Significant cardiac disease
Severe obesity (body mass index ≥40 kg/m2 )
Diabetes
Liver disease
HIV infection
Slide27Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Study Design
Source: Baden LR, et al. N Engl J Med. 2020 Dec
30. DOI: 10.1056/NEJMoa2035389
mRNA-1273 100
μg
(0.5 mL), 2 IM doses, 28 days apart
(n = 15,181)
Saline placebo, 2 IM doses, 28 days apart
(n = 15,170)
or
Study Participant Groups
Slide28Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baseline Characteristics: Gender Distribution for ALL Participants
Source: Baden LR, et al. N Engl J Med. 2020 Dec
30. DOI: 10.1056/NEJMoa2035389
Slide29Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baseline Characteristics: Age Distribution for ALL Participants
Age ≥65 Years
Age <65 Years,
not at risk for severe COVID-19
Age <65 Years,
at risk for severe COVID-19
Slide30Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baseline Characteristics, by Group
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Baseline Characteristics
Placebo
(N=15,170)
mRNA-1273
(N=15,181)
Sex — no. of participants (%)
Male
8,062 (53.1)
7,923 (52.2)
Female
7,108 (46.9)
7,258 (47.8)
Mean age (range) — years
51.3 (18–95)
51.4 (18–95)
Age category and risk for severe Covid-19 — no. (%)
18 to <65 years, not at risk
8,886 (58.6)
8,888 (58.5)
18 to <65 years, at risk
2,535 (16.7)
2,530 (16.7)
≥65 years
3,749 (24.7)
3,763 (24.8)
Risk factor for severe Covid-19 — no. of participants (%)
Chronic lung disease744 (4.9)710 (4.7)Significant cardiac disease744 (4.9)752 (5.0)Severe obesity1,021 (6.7)1,025 (6.8)Diabetes1,440 (9.5) 1,41,435 (9.5)Liver disease
96 (0.6) 10100 (0.7)HIV infection87 (0.6)92 (0.6)BMI, mean ± SD
29.3± 6.7
29.3±6.9
Slide31Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baseline Characteristics, by Group
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Baseline Characteristics
Placebo
(N=15,170)
mRNA-1273
(N=15,181)
Hispanic or Latino ethnicity — no. of participants (%)‡
Hispanic or Latino
3,114 (20.5)
3,121 (20.6)
Not Hispanic or Latino
11,917 (78.6)
11,918 (78.5)
Not reported and unknown
139 (0.9)
142 (0.9)
Race or ethnic group — no. of participants (%)‡
White
11,995 (79.1)
12,029 (79.2)
Black or African American
1,527 (10.1)
1,563 (10.3)
Asian
731 (4.8)
651 (4.3)
American Indian or Alaska Native
121 (0.8) 112 (0.7)Native Hawaiian or other Pacific Islander32 (0.2) 35 (0.2)Multiracial321 (2.1) 315 (2.1)Other316 (2.1) 321 (2.1)Not reported and unknown127 (0.8) 155 (1.0)
‡ Race or ethnic group was reported by the participant. Participants could be included in more than one category.
Slide32Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baseline Characteristics, by Group
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Baseline Characteristics
Placebo
(N=15,170)
mRNA-1273
(N=15,181)
Baseline SARS-CoV-2 status — no. of participants (%)§
Negative
14,598 (96.2)
14,550 (95.8)
Positive
337 (2.2)
343 (2.3)
Missing data
235 (1.5)
288 (1.9)
Baseline RT-PCR test — no. of participants (%)
Negative
14,923 (98.4)
14,917 (98.3)
Positive
95 (0.6)
87 (0.6)
Missing data
152 (1.0)
177 (1.2)
Baseline binding antibody anti–SARS-CoV-2 assay — no. of participants (%)
Negative14,726 (97.1)14,690 (96.8)Positive303 (2.0)305 (2.0)Missing data141 (0.9)186 (1.2)§Baseline SARS-CoV-2 status was positive if there was immunologic or virologic evidence of previous illness with Covid-19, as defined by a positive RT-PCR test or a positive binding antibody against SARS-CoV-2 at day 1.
Slide33Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Vaccine Efficacy
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30. DOI: 10.1056/NEJMoa2035389
Slide34Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Incidence Rate and Vaccine Efficacy, Based on Type of Analysis
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Slide35Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Incidence Rate and Vaccine Efficacy, Based on Age Group
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Vaccine Efficacy 95.6%
Vaccine Efficacy 86.4%
Slide36Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Vaccine Efficacy During Study, Modified Intention-to-Treat Analysis
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Slide37Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Vaccine Efficacy
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30. DOI: 10.1056/NEJMoa2035389
Endpoint
Placebo
(N=14,073)
mRNA-1273
(N=14,073)
Vaccine Efficacy*
Cases of Symptomatic Covid-19
Number (95% CI)
185
11
94.1%
(89.3-96.8, p<.001)
Incidence per1000 person-years (95% CI)
56.5
(48.7-65.3)
3.3
(1.7 to 6.0)
Secondary end point
Cases of severe Covid-19, n
30
0
100%
*Vaccine efficacy defined as 1 minus the hazard ratio (mRNA vs placebo)
Slide38Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Vaccine Efficacy– Subgroup analysis
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Subgroup
Placebo
(N=14,073)
no. of events/total no.
mRNA-1273
(N=14,134)
no. of events/total no.
Vaccine efficacy
(95% CI)
All patients
185/14,073
11/14,134
94.1 (89.3–96.8)
Age
≥18 to <65 years
156/10,521
7/10,551
95.6 (90.6–97.9)
>65
years
29/3552
4/3583
86.4 (61.4–95.2)
Age, risk for severe Covid-19
18 to <65
years
, not at risk121/84035/839695.9 (90.0–98.3)18 to <65 years, at risk35/21182/215594.4 (76.9–98.7≥65 years29/35524/3583
86.4 (61.4–95.2)SexMale
87/7462
4/7366
95.4 (87.4–98.3)
Female
98/6611
7/6768
93.1 (85.2–96.8)
At risk for severe Covid-19
Yes
43/3167
4/3206
90.9 (74.7–96.7)
No
142/10,906
7/10,928
95.1 (89.6–97.7)
Race and ethnic group
White
144/8916
10/9023
93.2 (87.1–96.4)
Communities of color
41/5132
1/5088
97.5 (82.2–99.7)
Slide39Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Injection-Site Adverse Events
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30. DOI: 10.1056/NEJMoa2035389
Slide40Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Safety, Localized Adverse Events (1)
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Localized Adverse Events
Grade 1
Grade 2
Grade 3
Any local adverse event, %
Placebo, dose 1
18.7
0.5
0.5
Placebo, dose 2
17.7
0.6
0.5
mRNA-1273, dose 1
70.8
9.9
3.5
mRNA-1273, dose 2
59.8
21.9
7.0
Pain
Placebo, dose 1
16.8
0.4
0.4
Placebo, dose 216.30.40.3mRNA-1273, dose 172.58.52.7mRNA-1273, dose 264.719.44.1ErythemaPlacebo, dose 10.3<0.1<0.1Placebo, dose 20.3<0.10.1mRNA-1273, dose 11.80.80.3mRNA-1273, dose 23.03.62.0
Slide41Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Safety, Localized Adverse Events (2)
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Localized Adverse Events
Grade 1
Grade 2
Grade 3
Swelling
Placebo, dose 1
0.3
<0.1
<0.1
Placebo, dose 2
0.2
<0.1
<0.1
mRNA-1273, dose 1
4.0
1.6
0.5
mRNA-1273, dose 2
6.1
4.4
1.7
Lymphadenopathy
Placebo, dose 1
4.4
0.2
0.2
Placebo, dose 23.60.20.1mRNA-1273, dose 19.20.70.3mRNA-1273, dose 211.81.90.5
Slide42Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Systemic Adverse Events
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30. DOI: 10.1056/NEJMoa2035389
Slide43Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Safety: Systemic Adverse Events (1)
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Systemic Adverse Events
Grade 1
Grade 2
Grade 3
Any systemic adverse event, % participants
Placebo, dose 1
28.7
11.5
2.0
Placebo, dose 2
24.2
10.4
1.9
mRNA-1273, dose 1
35.4
16.5
2.9
mRNA-1273, dose 2
25.4
38.1
15.8
Fever
Placebo, dose 1
0.2
<0.1
<0.1
Placebo, dose 20.2<0.1<0.1mRNA-1273, dose 10.50.2<0.1mRNA-1273, dose 29.34.81.4HeadachePlacebo, dose 121.83.51.3Placebo, dose 218.83.51.1mRNA-1273, dose 126.14.81.8mRNA-1273, dose 232.721.44.5
Slide44Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Safety: Systemic Adverse Events (2)
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Systemic Adverse Events
Grade 1
Grade 2
Grade 3
Fatigue
Placebo, dose 1
17.9
8.7
0.7
Placebo, dose 2
15.0
7.7
0.7
mRNA-1273, dose 1
23.7
12.4
1.0
mRNA-1273, dose 2
23.4
32.2
9.7
Myalgia
Placebo, dose 1
10.3
3.0
0.3
Placebo, dose 28.93.10.4mRNA-1273, dose 116.16.00.6mRNA-1273, dose 222.126.99.0ArthralgiaPlacebo, dose 18.92.70.2Placebo, dose 27.82.60.3mRNA-1273, dose 112.24.00.4mRNA-1273, dose 219.118.55.2
Slide45Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Safety: Systemic Adverse Events (3)
Source: Baden LR, et al. N Engl J Med. 2020 Dec 30.
DOI: 10.1056/NEJMoa2035389
Systemic Adverse Events
Grade 1
Grade 2
Grade 3
Nausea or vomiting
Placebo, dose 1
5.9
1.1
<0.1
Placebo, dose 2
5.2
1.1
<0.1
mRNA-1273, dose 1
6.9
1.3
<0.1
mRNA-1273, dose 2
14.2
4.6
0.1
Chills
Placebo, dose 1
4.7
1.0
<0.1
Placebo, dose 24.31.10.1mRNA-1273, dose 16.21.90.2mRNA-1273, dose 219.823.11.3
Slide46Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
: Additional notes
Source: Baden LR, et al. N Engl J Med. 2020 Dec
30. DOI: 10.1056/NEJMoa2035389Fewer occurrences of symptomatic SARS-CoV-2 infection were noted after a singe dose of mRNA-1273, though the trial was not designed to evaluate the efficacy of a single
dose
The magnitude of mRNA-1273 vaccine efficacy at preventing symptomatic SARS-CoV-2 infection is higher than the efficacy observed for vaccines for respiratory viruses (e.g. 59% efficacy seen for inactivated influenza vaccine)
No evidence in the short term of enhanced respiratory disease after infection
Slide47Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
: Limitations
Source: Baden LR, et al. N Engl J Med. 2020 Dec
30. DOI: 10.1056/NEJMoa2035389Short duration of safety and efficacy follow-upLack of an identified correlate of protectionInsufficient data to assess the incidence of asymptomatic or subclinical infection and viral shedding after infection
Pregnant women and children were excluded from this trial
Slide48Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
: Authors’ Conclusions
Source: Baden LR, et al. N Engl J Med. 2020
Dec 30. DOI: 10.1056/NEJMoa2035389
Conclusions
: “
The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified.”