A Booster mRNA Vaccine Required to Protect Against Omicron Variant

The Omicron (BA.1/B.1.1.529) COVID-19 variant is causing more breakthrough infections among vaccinated individuals than any prior COVID-19 strain.

COVID-19 vaccination works by sending neutralizing antibodies to attack the SARS-CoV-2 spike protein. The Omicron variant has up to 36 mutations in its spike protein, explaining its unprecedented resilience to the vaccines.

A recent study, published in Cell, confirmed that 2 doses of an mRNA-based vaccine (Pfizer-BioNTech or Moderna) do not adequately neutralize Omicron.

Investigators from the Ragon Institute of MGH, MIT and Harvard created a harmless “pseudovirus” version of Omicron that mimicked its mutations.

In laboratory experiments, they tested the efficacy of their pseudovirus against blood samples from 239 individuals vaccinated with an initial series of 1 of the 3 COVID-19 vaccines approved in the US: a 2-dose regimen of Pfizer-BioNTech or Moderna, or a 1-dose regimen of Janssen. The study group also included 70 individuals who received a third dose of an mRNA vaccine.

The investigators found that all 3 primary vaccine series produced little to no effective neutralization of the Omicron variant. However, those who received an mRNA booster dose had potent neutralization against Omicron.

The results also showed the Omicron pseudovirus uses the human ACE2 receptor for target cell entry, and infects target cells 4 times more effectively than the wild-type pseudovirus and 2 times more efficiently than Delta pseudovirus.

The investigators concluded, “Our finding of potent cross-neutralizing immunity against Omicron in individuals that received a third dose of mRNA vaccine suggests that existing vaccines may overcome evasion of humoral immunity by future variants of concern.”

In response to the emergence of the Omicron variant, the US Centers for Disease Control and Prevention (CDC), and US Food and Drug Administration (FDA) updated their COVID-19 vaccine recommendations.

Now, all persons 12 and older are strongly recommended to receive an additional mRNA booster vaccine:

• 6 months after initial vaccination for Moderna (mRNA-1273) recipients
• 5 months after initial vaccination for Pfizer-BioNTech (BNT162b)
  • Currently, Pfizer-BioNTech is the only COVID-19 vaccine approved for children and adolescents under 18 years
• 2 months after initial vaccination for Janssen (Johnson & Johnson; Ad26.COV2.S) recipients
  • Both mRNA vaccines are currently preferred over the Janssen vaccine, as boosters and as a primary series, though vaccination with Janssen is recommended if no other COVID-19 vaccine is available.