Evaluating effectiveness of the COVID-19 mRNA-1273 vaccine against Omicron and Delta variants

In a study recently published on the medRxiv* pre-print server, a team of researchers investigated the effectiveness of one to three doses of coronavirus disease 2019 (COVID-19) mRNA-1273 vaccine against the highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant vis-à-vis the Delta variant in a large, diverse, socio-economic population in Southern California. 

Study: Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants. Image Credit: Studio Romantic/ShutterstockStudy: Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants. Image Credit: Studio Romantic/Shutterstock

Although data on real-world vaccine effectiveness (VE) of mRNA-1273 against Omicron infections is limited, several past studies have reported high and durable VE of mRNA-1273 against COVID-19 due to other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including the Delta (B.1.617.2) variant.

About the study

In the present study, researchers assessed the VE against Omicron and Delta variant-induced infection as well as hospitalization, including among immunocompromised individuals.

The authors collected test-positive and test-negative samples (controls) of individuals over 18 years between 6-23 December 2021. Randomly sampled test negative controls were 5:1 matched to test-positive cases by age, sex, race/ethnicity, and specimen collection date. Matching among test samples was conducted separately for the 1-, 2-, and 3-dose VE analysis.

The researchers confirmed test-positive cases by reverse transcription-polymerase chain reaction (RT-PCR) and variant infection by spike (S) gene status. Since Omicron has a mutated S protein, Omicron-positive test samples exhibited S gene target failure (SGTF), used as a marker for Omicron in study analyses, which showed the proportion of SGTF among SARS-CoV-2 positive samples increased from 2.7% to 83.9% during the study period.


During the study period, an unprecedented increase in Omicron infections raised concerns over protection conferred by currently used COVID-19 vaccines. 

The two- and three-dose mRNA-1273 analyses showed that compared to the Delta variant cases, Omicron cases appeared more frequently in the younger population and individuals with a history of COVID-19.

Subsequently, the results of two-dose and three-dose analyses among 18-44 year-olds showed 73.9% and 73.2% of Omicron cases, respectively, compared to 59.2% and 61.4% of Delta cases. Moreover, 13.0% and 14.9% of Omicron cases in the 2- and 3-dose analyses, respectively, had a history of COVID-19 versus 1.7% and 2.2% of Delta cases. Overall, the 1- dose VE was 60.2% and 20.3%, the 2-dose VE was 60.7% and 0.0%, and the 3-dose VE was 95.2% and 62.5% against the Delta and Omicron infection, respectively.

In analyses of two-dose VE against Delta and Omicron infection, VE against Delta declined slowly from 82.8% at 14-90 days to 52.9% in ~270 days, and VE against Omicron declined sharply from 30.4% at 14-90 days to 0% in 180 days. After the third dose, VE against Delta infection was more than 90%, regardless of the time of receipt of the vaccine dose. However, VE against Omicron fell sharply after the third dose from 63.6% (after 20 October 2021) to 39.1% (on or before 20 October 2021). VE against Omicron infection increased to 49.0% among immunocompetent individuals who received the third dose on or before 20 October 2021.

Individuals vaccinated with three vaccine doses were not hospitalized, regardless of Omicron or Delta variant infection. However, among individuals vaccinated with one or two vaccine doses, four Delta-infected and two Omicron-infected individuals were hospitalized. 

The VE of the third dose against the Delta variant was more than 95% across age, sex, and race/ethnicity groups but only 72.2% in the immunocompromised population. In adults over 65 years, the VE of dose three against the Omicron variant was 63.1%. However, it was 11.5% in the immunocompromised individuals and 63.6% in the immunocompetent individuals.


In summary, the study findings demonstrated while the VE of two doses of mRNA-1273 waned against the Delta variant, it remained high and durable after three doses. Contrastingly, VE of both two- and three doses of mRNA-1273 remained low against the Omicron variant, demonstrating that protection against Omicron waned quickly within three months after the second dose, suggesting the need for a shorter time interval between the second and booster doses. As VE against Omicron infection was particularly low among immunocompromised individuals, the authors recommend a fourth vaccine dose (booster) for this at-high risk population. 

The researchers recommend that the emergence of newer SARS-CoV-2 variants and VE against Omicron are continually monitored, particularly in immunocompromised individuals, as surveillance would help devise robust vaccination strategies in the future. They also recommended a long-term follow-up to evaluate the durability of the third dose of a vaccine in preventing infection and hospitalization among adults and immunocompromised individuals.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.


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