High-titer neutralization of Mu and C.1.2 SARS-CoV-2 variants by vaccine-elicited antibodies of previously infected individuals

Recently identified SARS-CoV-2 variants Mu and C.1.2 have spike proteins with mutations that might confer resistance to natural and vaccine-elicited antibodies. Analysis of neutralizing antibody titers in the sera of vaccinated individuals without previous history of infection and from convalescent individuals showed partial resistance of the viruses. In contrast, sera from individuals with a previous history of SARS-CoV-2 infection who were subsequently vaccinated, neutralized variants with titers 4-11-fold higher, providing a rationale for vaccination of infection-experienced individuals. The heavily mutated C.1.2 spike was the most antibody neutralization-resistant spike to date; however, the avidity of C.1.2 spike protein for ACE2 was low. This finding suggests that the virus evolved to escape the humoral response but has a decrease in fitness suggesting that it may cause milder disease or be less transmissible. It may be difficult for the spike protein to evolve to escape neutralizing antibodies while maintaining high affinity for ACE2.
Graphical Abstract
Tada et al. show that infection with SARS-CoV-2 followed by vaccination results in broadly neutralizing antibody. The C.1.2 variant has a highly mutated spike and is the most neutralization-resistant variant; however, its affinity for ACE2 is decreased. Thus, the virus cannot evolve to escape humoral response without becoming less fit.