In SARS-CoV-2 unvaccinated cases, Omicron infection shows limited cross-reactive neutralization against other variants

A group from Gladstone Institutes, San Francisco, CA, USA, etc. has reported that infection with Omicron variant in unvaccinated individuals may not elicit effective cross-neutralizing antibodies against other variants. In vaccinated individuals, however, Omicron infection effectively induces immunity against itself and enhances protection against other variants.

To determine humoral immune responses induced by infection with the three different strains, sera from infected mice and tested their neutralization efficiency against SARS-CoV-2 strains were collected: WA1, Alpha, Beta, Delta, and Omicron. Efficient virus neutralization was defined by more than 50% reduction in plaque forming units at the lowest serum dilutions. Sera from Delta-infected mice showed the broadest cross-variant neutralization, effectively neutralizing all the strains except Beta. By contrast, while Omicron infection effectively neutralized Omicron itself, it exhibited limited (<50%) cross-neutralization of other strains. Sera from WA1-infected mice conferred effective protection against WA1, Alpha, and Delta, but not against Beta and Omicron. These results indicate limited immunity induced by Omicron relative to other strains, which may be due to its highly mutated spike protein or its lower replicative capacity. In human cases, interestingly, sera from vaccinated individuals with confirmed Omicron breakthrough infection showed the highest level of protection (>80%) against all strains, including Omicron as shown below.