Study indicates a 100 µg mRNA-1273 booster has acceptable safety and robust antibody response against SARS-CoV-2

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Mar 11 2022

A recent study posted to the medRxiv* preprint server assessed the safety and immunogenicity of messenger ribonucleic acid (mRNA)-1273 booster vaccine against coronavirus disease 2019 (COVID-19).

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

The global public health crisis caused by the widespread morbidity and mortality due to COVID-19 is being efficiently curbed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. However, booster vaccine doses are now recommended, with emerging reports of waning vaccine effectiveness. 

About the study

The present study was part B of an ongoing phase 2/3 study investigating the reactogenicity, immunogenicity, and safety of 100 µg of mRNA-1273 booster dose one month after vaccine administration.

The study included a total of 300 participants aged 18 years and older who had received the primary vaccine series of mRNA-1273 at least six months before the study. These participants were enrolled from eight clinical sites across the US between 3 August and 16 August 2021. On day 1, the eligible participants received a booster dose of 100 µg mRNA-1273. The mRNA-1273 vaccine was a lipid nanoparticle that had the mRNA that encodes for the SARS-CoV-2 Wuhan strain spike (S) glycoprotein.

The primary safety outcomes of this study were systemic and local adverse reactions (ARs) reported by the participants for seven days post booster vaccination. Other treatment-emergent adverse events (TEAEs) were also reported for 28 days after the booster dose administration. AEs of special interest (AESIs), serious adverse events (SAEs), and medically attended adverse events (MAAEs) are being recorded for approximately 12 months post booster vaccination. 

The primary immunogenicity outcome was the demonstration of a non-inferior immune response of the mRNA vaccine against the SARS-CoV-2 S D614G variant 28 days post booster dose administration as compared to the immune response elicited by the second dose of the primary mRNA vaccine series 28 days post-vaccination in a control group. The control group included 584 participants who were vaccinated with the two doses of the primary mRNA-1273 vaccine.  

Results

The study results showed that a total of 305 participants were included in the safety assessment cohort, while 257 participants were included in the immunogenicity group. The mean ages of the recipients of the booster dose and the control group were 54.2 years and 52.1 years, respectively. The percentage of individuals in the control group and the booster group belonging to the White community was 72% and 92%, while 31% and 22% belonged to the Hispanic community, respectively.

For the assessment of the safety of the booster vaccine, a median follow-up time of 66 days was maintained after administration of the dose. The most commonly reported local AR was injection site pain of mild severity, occurring in 92.7% of total participants. Among systemic ARs, 72.8% of the recipients reported fatigue, 67.5% reported myalgia, and 61.9% reported headaches.

A higher number of incidences of swelling or tenderness post the 100-µg booster administration was observed as compared to after the second dose of the primary 100 µg mRNA-1273 vaccine series and after the administration of 50 µg booster injection. Moreover, a higher occurrence of solicited systemic responses was observed with the 100-µg booster dose than the 50-µg booster dose. However, the severity and incidence of these responses were comparable to those occurring after the primary vaccine series.

Unsolicited AEs were also observed up to 28 days after the injection of the 100-µg booster, among which 16.4% of events occurred regardless of the correlation to the vaccination. In contrast, 5.9% were considered to be correlated to the vaccination. Six SAEs occurred during the study, including one fatal case of cardiopulmonary arrest nine days after and a cerebrovascular accident occurring four days after the booster injection.

Immunogenicity assessment found geometric mean antibody titers (GMTs) of 9.3 before vaccination which improved to 4039.5 after 28 days post-booster vaccination. The geometric mean fold rise (GMFR) 28 days post booster dose was 440.2 compared to before vaccination and 45.0 compared to before booster dose administration.

Compared to the control cohort, the GMT was 1132.0, 28 days after the second vaccine dose in the primary series. Moreover, the geometric mean titer ratio (GMR) of the titers of booster dose and second vaccine dose post 28 days was 3.6. Also, GMTs of the 100-µg booster dose post 28 days of vaccination were higher than those after the administration of the 50-µg booster dose.

Conclusion

The study findings showed that the administration of the 100-µg mRNA-1273 booster dose at least six months post-primary vaccination can provide efficient protection against the SARS-CoV-2 Wuhan strain and variants of concern. While the clinical implications of 100 µg mRNA-1273 booster doses need further investigation, they can prove vital in eliciting higher antibody generation in crucial cases.  

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources