Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5

Area of Science:

• Virology and Immunology
• Vaccine Effectiveness Research
• Epidemiology of Infectious Diseases

Background:

• Emergence of SARS-CoV-2 omicron subvariants (BA.4/BA.5) with potential immune escape properties.
• Previous studies indicate reduced neutralization against omicron BA.4/BA.5.
• Need to assess the real-world effectiveness of mRNA-1273 vaccine against circulating omicron subvariants.

Purpose of the Study:

• To evaluate the vaccine effectiveness (VE) of the mRNA-1273 vaccine against SARS-CoV-2 infection and hospitalization.
• To compare VE across different omicron subvariants (BA.1, BA.2, BA.2.12.1, BA.4, BA.5).
• To assess the durability of protection after primary vaccination and a fourth dose.

Main Methods:

• Test-negative case-control study design.
• Inclusion of 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years.
• Data collected between January 1, 2022, and June 30, 2022.

Main Results:

• Three-dose VE against BA.1 infection was high and waned slowly; VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection was initially moderate-to-high but waned rapidly.
• Four-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranged from 64.3%-75.7%, and was low (30.8%) against BA.5, disappearing beyond 90 days.
• Three-dose VE against hospitalization was high for BA.1 (97.5%), moderate for BA.2 (82.0%), and lower for BA.4/BA.5 (72.4%); four-dose VE against BA.4/BA.5 hospitalization was 88.5%.

Conclusions:

• mRNA-1273 vaccine provides substantial protection against hospitalization, even with BA.4/BA.5 subvariants, particularly with a fourth dose.
• Rapid waning of infection protection against newer omicron subvariants highlights the need for updated vaccine formulations.
• Evaluation of updated bivalent COVID-19 boosters is recommended to address evolving viral characteristics.