What is the mRNA-1273 coronavirus disease 2019 (COVID-19) vaccine?

Updated: Sep 24, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: John L Brusch, MD, FACP  more...
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Answer

Overview

  • EUA in the United States for adults aged 18 years and older
  • EUA submitted June 10, 2021 for adolescents based on phase 2/3 TeenCOVE trial (n = 3,732) completed in adolescents aged 12-17 years showing 100% efficacy after 2 doses 
  • June 1, 2021: Rolling BLA initiated for U.S. licensure in adults
  • NIH  phase 2 trial of allergic reactions to vaccine in participants with severe allergies underway
  • US phase 3 trial (COVE) in adults complete 
  • Phase 2/3 KidCOVE trial children aged 6 months and older began in March 2021 (target enrollment 6,750)
  • Phase 2 study started for booster vaccine candidates
  • Phase 3 trial in university students planned to assess nasal viral load and shedding

The mRNA-1273 vaccine (Moderna) encodes the S-2P antigen. It is administered as a 2-dose series given 28 days apart. The US phase 3 trial (COVE) launched in July 2020. The trial was conducted in cooperation with the National Institute of Allergy and Infectious Diseases and included more than 30,000 participants who received two 100-mcg doses or matched placebo on days 1 and 29. Overall efficacy was 94.1% for the original viral strain. There were 196 confirmed cases (placebo group, 185; vaccine group, 11). Among the 185 cases in the placebo group, 30 cases were severe, including 1 death. [17]   

The COVE study (n = 30,420) included Americans 65 years and older (24.8%), younger individuals with high-risk chronic diseases (16.7%), individuals who identify as Hispanic or Latinx (20.5%), and individuals who identify as Black or African American (10.4%). [17]  At 6 months after the second dose, efficacy was greater than 90% against COVID-19 infection and greater than 95% against severe COVID-19 in identified cases (data adjudicated from over 900 cases, of which over 100 were severe). [18]

In an ongoing phase 1 trial, 33 adult participants in all age groups showed high antibody activity elicited by mRNA-1273 at 6 months after the second dose. [19]  

Third Dose

As of August 2021, recommendations regarding administering a third dose are not established. Quantitative data are not yet available to guide clinicians as to determine a specific patient should receive a third dose. Additionally, data are not yet available regarding efficacy and safety of administering a third dose. 

An adaptive trial (NCT04889209) is underway to assess the safety, reactogenicity, and immunogenicity of a delayed (>/=12 weeks) vaccine boost includes all 3 vaccines granted EUAs in the United States. This study will look at mixed boosted regimens. The results are intended to assist with public health policy decisions should booster doses be indicated. 

Studies in immunocompetent individuals 

mRNA-1273 vaccine

A third dose of mRNA-1273 or mRNA-1273.351 (a strain-matched vaccine candidate) increased neutralizing titers against SARS-CoV-2 and 2 variants of concern (B.1.351, P.1) in previously vaccinated clinical trial participants. The third dose of mRNA-1273.351 achieved higher titers against B.1.351 compared with mRNA-1273. [22]

Evaluation of a multivalent vaccine booster, mRNA-1273.211, that combines mRNA-1273 ancestral strains and mRNA-1273.351 in a single vaccine is ongoing. 

Studies in immunocompromised individuals

The mRNA vaccines are highly effective in the general population. As with other vaccines, it is important to determine if immunosuppressed populations (eg, patients who have cancer, are solid organ transplant recipients, on hemodialysis, and/or taking immunosuppressive therapies) are able to mount a sufficient immunologic response following 2 doses mRNA vaccine. Data are emerging and as of August 2, 2021, the mRNA vaccines’ EUAs in the United States have not been amended to suggest a third dose. 

Solid organ transplant recipients

A case series of 7 solid organ transplant recipients describes confirmed COVID-19 infection after receiving an mRNA vaccine. Two individuals had received 1 dose and the others had received 2 doses. Six patients were tested for antispike antibodies, of which 5 had undetectable levels and 1 patient who had received his second mRNA-1273 vaccine 44 days prior, had low titer antispike antibody. None of these 6 patients had detectable nucleocapsid antibody. [25] Others have confirmed low or nondetectable antispike antibody levels and nucleocapsid antibodies. [26, 27] These reports prompted the French National Authority for Health to recommend the use of a third dose in immunosuppressed patients. 

Kamar et al reported results of the humoral response of 101 consecutive solid-organ transplant recipients given a third dose of mRNA vaccine (BNT-152b2; Pfizer) 61 days after the second dose. Prevalence of anti–SARS-CoV-2 antibodies was 0% before the first dose, 4% before the second dose, 40% before the third dose, and 68% 4 weeks after the third dose. Among the 59 patients who had been seronegative before the third dose, 26 (44%) were seropositive at 4 weeks after the third dose. All 40 patients who had been seropositive before the third dose were still seropositive 4 weeks later, and their antibody titers increased from 36±12 before the third dose to 2676±350 at 1 month after the third dose (P < 0.001). Patients who did not have an antibody response were older, had a higher degree of immunosuppression, and had a lower estimated glomerular filtration rate compared with patients who had an antibody response. [29]    

Patients on maintenance hemodialysis 

A national registry in France was used to compare severity of 1,474 COVID-19 cases in patients on maintenance hemodialysis (MHD) after 0, 1, or 2 doses of BNT162b2 vaccine. Overall, vaccination reduced disease severity, but 11% of infected patients who had received 2 doses died. Patient on MHD with humoral response similar to healthy volunteers after 2 doses did not generate more immune effectors after a third dose, but and had more side effects. In contrast, 66% of patients on MHD with suboptimal response after 2 doses reached an optimal titer of anti-RBD IgG and/or developed spike-specific CD8+ T cells after a third dose. [30]  


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