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What does the evidence say on the safety and efficacy of the mRNA-1273 vaccine (Moderna Vaccine) in preventing SARS-CoV-2 infection?

Comment by InpharmD Researcher

The Moderna Vaccine, mRNA-1273, has shown a 94.1% efficacy rate with no severe safety concerns when compared to placebo.
Background

A review article assessing the rationale for the development of mRNA-based SARS-CoV-2 vaccines stated that limitations of such a vaccine may include repeated vaccine administrations, cross-reactive T-cell receptors and antibodies, bystander activation of pre-existing effector or memory cells, possible unfavorable classical cell-mediated immunity, and high glycosylation of the viral envelope. Additionally, the possibility of inducing infection is present. While these limitations do exist, there are four main advantages to an mRNA vaccine: 1) minimization of the potential risk of infection and insertion-induced mutagenesis due to natural degradation of mRNA in the cellular microenvironment; 2) improved stability and translation efficacy due to the immunogen's high efficacy due to engineered mRNA structural modifications; 3) high potency of mRNA-based vaccines capable of generating potent antiviral neutralizing immunoglobulins with only one or two low-dose immunizations which may induce strong immune responses by activating both CD8+ and CD4+ T cells; 4) engineered mRNA production facilitates large-scale production of sufficient vaccine doses required to treat mass populations. [1]

References:

[1] Wang F, Kream RM, Stefano GB. An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development. Med Sci Monit. 2020;26:e924700. Published 2020 May 5. doi:10.12659/MSM.924700

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What does the evidence say on the safety and efficacy of the mRNA-1273 vaccine (Moderna Vaccine) in preventing SARS-CoV-2 infection?

Please see Table 1 for your response.


 

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Design

Preliminary analysis of a randomized, observer-blinded, placebo-controlled, phase 3 clinical trial

N=28,207

Objective

To assess the safety and efficacy of the mRNA-1273 vaccine (Moderna vaccine) in preventing SARS-CoV-2 infection

Study Groups

Moderna Vaccine (n=14,134)

Placebo (n=14,073)

Inclusion Criteria

Aged ≥18 years, considered to be at high risk of SARS-CoV-2 infection (due to locations or circumstances), were healthy or had pre-existing medical conditions who are in stable condition (defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment), females with a negative pregnancy test, females and males who agreed to practice adequate contraception or has abstained from all activities that could result in pregnancy during the trial period

Exclusion Criteria

Persons who were acutely ill or febrile (≥38.0°C/100.4°F) 72 hours prior to screening; were pregnant or breastfeeding; had a known history of SARS-CoV-2 infection; had a history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine; had received or plans to receive a non-study vaccine within 28 days (except for seasonal influenza vaccine); had an immunosuppressive or immunodeficient state (including HIV infection, asplenia, and recurrent severe infections); received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to screening (≥20 mg equivalents of prednisone per day); received systemic immunoglobulins or blood products within 3 months prior to screening

Methods

Participants were randomized 1:1 to receive two intramuscular injections of mRNA-1273 (100 μg/0.5 mL) or saline placebo 28 days apart. Group assignment was stratified based on age and COVID-19 risk criteria.

This is a preliminary, per-protocol analysis of participants who received both injections. Vaccine efficacy was defined as 1 - hazard ratio.

The vaccines were stored at 2° to 8°C (35.6° to 46.4°F) at clinical sites before preparation and vaccination. No dilution was required. Doses could be held in syringes for up to 8 hours at room temperature before administration.

Duration

July 27 to November 25, 2020 (interim analysis cut-off date)

Follow-up: up to 28 days post-injection

Long-term follow-up: up to 759 days post-injection

Outcome Measures

Safety: solicited and unsolicited local and systemic adverse events

Primary efficacy: a first occurrence of symptomatic COVID-19 with onset at least 14 days after the second injection

Baseline Characteristics

 

Placebo (n=14,073)

Moderna Vaccine (n=14,134)

 

Age, years (range)

18-65 years, not at risk

18-65 years, at risk

≥65 years

51.6 (18-95)

8,200 (58.3%)

2,324 (16.5%)

3,549 (25.2%)

51.6 (18-95)

8,189 (57.9%)

2,367 (16.7%)

3,578 (25.3%)

 

Male

7,432 (53%) 7,366 (52.1%)  

Body mass index, kg/m2

29.27 ± 6.65 29.28 ± 6.83  

Risk factors for severe COVID-19

Chronic lung disease

Significant cardiac disease

Severe obesity

Diabetes

Liver disease

HIV

 

4.9%

4.9%

6.7%

9.6%

0.6%

0.5%

 

4.8%

5.0%

6.8%

9.7%

0.7%

0.6%

 
Of the population, 79.5% were White and 79.3% did not identify as Hispanic or Latino.

Results

 

Placebo (n=14,073)

Moderna Vaccine (n=14,134)

Vaccine efficacy

Symptomatic COVID-19 within 14 days of the second dose 185 (65.5 per 1000 person-years) 11 (3.3 per 1000 person-years) 94.1%
Severe COVID-19 30 (0.2%) 0 100%
COVID-19 after the first dose 225 (1.6%) 11 (0.078%) 95.2%
Any COVID-19 symptoms within 14 days of the second dose 221 (1.6%) 11 (0.078%) 95.1%

The primary efficacy endpoint corresponds to a vaccine efficacy of 94.1% (95% confidence interval [CI] 89.3% to 96.8%; P<0.001). Subgroup analyses of age groups (18-65 years and ≥65 years), presence of risk for severe Covid-19, sex, and race/ethnic group (non-Hispanic White and communities of color) showed consistent results.

Of the modified intention-to-treat population, 54 patients tested positive (via RT-PCR) for COVID-19 at the scheduled second dose (39 vs 15). This corresponds to a vaccine efficacy of 89.6% (95% CI 85.2% to 92.6%) in this population.

Adverse Events

Overall data set

Placebo (n=15,166)

Moderna Vaccine (n=15,185)  

Any solicited AEs

After first injection

After second injection

 

48.1%

42.8%

 

87.8%

92.2%

 

Injection-site pain

After first injection

After second injection

 

17.5%

17.0%

 

83.7%

88.2%

 

Fatigue

After first injection

After second injection

 

27.3%

23.3%

 

37.2%

65.3%

 

Other common solicited AEs: axillary swelling/tenderness, headache, myalgia, arthralgia, chills, nausea/vomiting

Solicited systemic adverse events in the mRNA-1273 group lasted a mean of 2.9 days and 3.1 days after the first and second doses, respectively.

Any unsolicited AEs

Headache

Cough

Oropharyngeal pain

Diarrhea

21.6%

30%

1.0%

1.3%

1.1%

23.9%

3.1%

1.1%

1.0%

1.2%

 
Hypersensitivity (any severity) 1.1% 1.5%  

Both solicited injection-site and systemic adverse events were more common among younger participants (18 to 65 years) than among older participants (≥65 years).

Study Author Conclusions

The mRNA-1273 vaccine (Moderna 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.

InpharmD Researcher Critique

A large limitation of this analysis is the short duration of safety and efficacy follow-up, as the trial is still ongoing. The primary efficacy data was conducted in a per-protocol population, as the modified intention-to-treat population appeared to show a lower vaccine efficacy; however, this population had only received their first dose. While this data is promising, results from the full analysis will determine the true efficacy and safety of the Moderna COVID-19 Vaccine.



References:

Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine [published online ahead of print, 2020 Dec 30]. N Engl J Med. 2020;NEJMoa2035389. doi:10.1056/NEJMoa2035389