ABSTRACT Severe acute respiratory syndrome coronavirus 2 variants have continued to emerge in diverse geographic locations with a temporal distribution. The Lambda variant containing multiple mutations in the spike protein, has thus far appeared mainly in South America. The variant harbours two mutations in the receptor binding domain, L452Q and F490S, which may change its infectivity and antigenicity to neutralizing antibodies. In this study, we constructed 10 pseudoviruses to study the Lambda variant and each individual amino acid mutation’s effect on viral function, and used eight cell lines to study variant infectivity. In total, 12 monoclonal antibodies, 14 convalescent sera, and 23 immunized sera induced by mRNA vaccines, inactivated vaccine, and adenovirus type 5 vector vaccine were used to study the antigenicity of the Lambda variant. We found that compared with the D614G reference strain, Lambda demonstrated enhanced infectivity of Calu-3 and LLC-MK2 cells by 3.3-fold and 1.6-fold, respectively. Notably, the sensitivity of the Lambda variant to 5 of 12 neutralizing monoclonal antibodies, 9G11, AM180, R126, X593, and AbG3, was substantially diminished. Furthermore, convalescent- and vaccine-immunized sera showed on average 1.3–2.5-fold lower neutralizing titres against the Lambda variant. Single mutation analysis revealed that this reduction in neutralization was caused by L452Q and F490S mutations. Collectively, the reduced neutralization ability of the Lambda variant suggests that the efficacy of monoclonal antibodies and vaccines may be compromised during the current pandemic.
【저자키워드】 SARS-CoV-2, Vaccines, neutralization, monoclonal antibodies, Lambda variant, C.37, convalescent serum, 【초록키워드】 severe acute respiratory syndrome coronavirus 2, Efficacy, Vaccine, coronavirus, pandemic, Mutation, Neutralizing antibodies, neutralization, monoclonal antibody, mutations, variant, monoclonal antibodies, Spike protein, Receptor binding domain, mRNA vaccines, Adenovirus, sensitivity, Viral, Inactivated vaccine, sera, D614G, Neutralizing, antigenicity, respiratory, convalescent, distribution, South America, Calu-3, convalescent sera, neutralizing monoclonal antibodies, Lambda, Amino acid, Analysis, cell lines, temporal distribution, geographic locations, pseudoviruses, reference strain, acute respiratory syndrome, acute respiratory syndrome coronavirus, average, geographic location, titre, multiple mutations, Calu, cell line, neutralization ability, R126, Cell, immunized, caused, eight, reduced, were used, the spike protein, demonstrated, reduction in, multiple mutation, pseudovirus, 【제목키워드】 neutralizing antibody, vaccination, monoclonal antibody, Infection, sensitivity, the SARS-CoV-2,