The study investigates the immune response to the SARS-CoV-2 Omicron variant, which has 34 mutations in the spike protein, more than other variants. The research, conducted by a team from Massachusetts General Hospital and other institutions, found that two doses of mRNA-based vaccines (mRNA-1273, BNT162b2, or Ad26.COV2.S) were insufficient to effectively neutralize the Omicron variant, with neutralization titers being undetectable in most vaccinees. However, individuals who received a third dose of mRNA vaccine exhibited potent neutralization of the Omicron variant, with titers only 4–6 times lower than those against wild-type. Additionally, the Omicron pseudovirus was found to infect cells more efficiently than other variants, suggesting enhanced infectivity. The study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent variants like Omicron.The study investigates the immune response to the SARS-CoV-2 Omicron variant, which has 34 mutations in the spike protein, more than other variants. The research, conducted by a team from Massachusetts General Hospital and other institutions, found that two doses of mRNA-based vaccines (mRNA-1273, BNT162b2, or Ad26.COV2.S) were insufficient to effectively neutralize the Omicron variant, with neutralization titers being undetectable in most vaccinees. However, individuals who received a third dose of mRNA vaccine exhibited potent neutralization of the Omicron variant, with titers only 4–6 times lower than those against wild-type. Additionally, the Omicron pseudovirus was found to infect cells more efficiently than other variants, suggesting enhanced infectivity. The study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent variants like Omicron.