Safety and Efficacy of CVnCoV, a 2-Dose Unmodified mRNA Vaccine for COVID-19

Flu shot or COVID vaccine shot
Syringe and hand closeup. The concept of vaccination, filling the drug into the syringe. Doctor background.
Researchers conducted a study to assess the safety and clinical efficacy of the CVnCoV mRNA COVID-19 vaccine candidate.

The CVnCoV mRNA COVID-19 vaccine was found to be safe and efficacious for protection against SARS-CoV-2 infection, regardless of disease severity. These findings were published in The Lancet Infectious Diseases.

In an ongoing, randomized, observer-blinded, placebo-controlled trial conducted at 47 centers in Europe and Latin America, researchers sought to assess the safety and efficacy of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. Study participants (N=39,680) were randomly assigned in a 1:1 fashion to receive either the CVnCoV vaccine (n=19,783) or placebo (n=19,746) on days 1 and 29. CVnCoV is a chemically unmodified mRNA vaccine. Safety and efficacy were assessed through 1 year.

Among participants in both the vaccine and placebo groups, 54.9% and 54.8% were men, 87.3% and 87.3% were aged 18 to 60 years, and 86.4% and 86.0% were seronegative for SARS-CoV-2 infection at baseline, respectively.

The primary efficacy analysis included 12,851 participants from the vaccine group and 12,211 from the placebo group. Participants who requested to be unmasked within 15 days of receiving the second CVnCoV vaccine dose were excluded from the analysis. Of note, requests to be unmasked occurred more frequently among participants aged 60 years and older vs those aged 18 to 60 years (69.8% vs 31.6%).

Following a mean observation period of 48.2 days, a total of 228 participants developed COVID-19. Of the participants who developed COVID-19, 83 were in the vaccine group and 145 were in the placebo group, indicating that the CVnCoV vaccine had an overall efficacy of 48.2% (95.826% CI, 31.0-61.4; P =.016).

On analysis of COVID-19 severity, the researchers found that mild COVID-19 comprised 79% of COVID-19 diagnoses among participants aged 18 to 60 years. Diagnoses of moderate or severe COVID-19 occurred among 49 participants in the vaccine group and 7 in the placebo group, indicating the vaccine had an efficacy of 70.7% (95.826% CI, 42.5-86.1) against severe disease.

In regard to SARS-CoV-2 variants among participants who developed COVID-19, 50% were infected with a variant of concern and 35% were infected with a variant of interest. Among participants aged 18 to 60 years, the researchers found that the efficacy of the CVnCoV vaccine was 55.1% among those with the Alpha variant, 67.1% among those with the Gamma variant, and 52.8% among those with the Lambda variant.

Among participants in both the vaccine and placebo groups, 96.5% and 67.9% reported at least 1 solicited adverse event and 50.3% and 45.2% reported at least 1 unsolicited adverse event, respectively. Of note, 8 severe adverse events occurred among 5 participants in the vaccine group, including acute myocardial infarction, atrial fibrillation, cardiac arrest, supraventricular extrasystoles and ventricular tachycardia, appendicitis, cellulitis, and seizure. Although the prevalence of solicited and unsolicited adverse events was increased among participants who received the CVnCoV vaccine vs those who received placebo, the events were temporary and most were of mild-to-moderate severity.

This study was limited by its insufficient population of unvaccinated participants who were aged 61 years and older due to the prioritization of older adults in national COVID-19 vaccination programs.

In regard to the emergence of diverse SARS-CoV-2 variants with increased transmissibility, the researchers concluded that “broad geographical representation should…be considered when designing future studies evaluating the efficacy of SARS-CoV-2 vaccines.”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Kremsner PG, Guerrero RAA, Arana-Arri E, et al. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial.