Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Omicron variants (BA.1, BA.1.1, BA.2) possess numerous spike mutations potentially reducing SARS-CoV-2 vaccine effectiveness.
• The Moderna mRNA-1273 vaccine's efficacy against Omicron requires evaluation, especially regarding boosting strategies.

Purpose of the Study:

• To assess the protective efficacy of the Moderna mRNA-1273 vaccine against SARS-CoV-2 Omicron BA.1 in mice.
• To compare the effects of a standard vaccine versus an Omicron-matched vaccine, with or without boosting, on protection against Omicron variants.

Main Methods:

• Mice were vaccinated with either mRNA-1273 or an Omicron-matched mRNA-1273.529 vaccine, receiving a primary series and/or a booster dose.
• Vaccinated mice were challenged with SARS-CoV-2 Omicron BA.1.
• Neutralizing antibody titers, lung inflammation, viral burden, and cytokine levels were measured post-challenge.

Main Results:

• Two doses of mRNA-1273 induced lower neutralizing antibodies against BA.1 compared to historical strains, leading to breakthrough infections and lung inflammation.
• An Omicron-matched vaccine (mRNA-1273.529) showed potent neutralization of BA.1 but less effectiveness against other variants.
• Boosting with either mRNA-1273 or mRNA-1273.529 significantly increased neutralizing titers and protection against BA.1 and BA.2.
• Mice boosted with mRNA-1273.529 exhibited slightly higher neutralizing antibody titers and lower lung viral burden and cytokines when challenged with BA.1 compared to those boosted with mRNA-1273.

Conclusions:

• Boosting with either the standard mRNA-1273 or the Omicron-matched mRNA-1273.529 vaccine enhances protection against SARS-CoV-2 Omicron (BA.1 and BA.2) infection.
• While both boosting strategies are effective, the Omicron-matched vaccine may offer a slight advantage in terms of neutralizing antibody response and reduced inflammation.
• The study highlights the importance of updated vaccine formulations or boosting for maintaining protection against rapidly evolving SARS-CoV-2 variants.