Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination

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.

KEYWORDS:

• SARS-CoV-2
• Lambda variant
• C.37
• neutralization
• vaccines
• convalescent serum
• monoclonal antibodies

Acknowledgments

We sincerely thank the laboratories and associated researchers who obtained the original samples and viral sequence information, as well as those who uploaded and shared genomic data through GISAID. These samples and data were critical to this study and were the cornerstone that allowed this study to proceed smoothly. This work was supported by the Beijing Municipal Science and Technology Project (Z211100002521018), National Natural Science Foundation of China (82073621, 82172244 and 32070678), National Key Research and Development Programme of China (2021YFC0863300) and the Bill and Melinda Gates Foundation (INV-006379).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Y.W., L.Z., and W.H. conceived, designed, and supervised the experiments; Q.L., L.Z., B.W., X.S., W.H., and Y.W. wrote the manuscript; M.W., Z.L., Y.S., J.W., and J.N. performed the experiments and analysed the data. B.W. and X.S. performed the structural analysis. Y.L. provided vaccine-immunized sera and patient information. X.Q. provided the convalescent sera and patient information. All of the authors approved the final manuscript.

Declaration of interests

All authors declare no competing interest.

Additional information

Funding

This work was supported by Bill and Melinda Gates Foundation: [Grant Number INV-006379]; National Natural Science Foundation of China: [Grant Number 82073621, 82172244 and 32070678]; National Key Research and Development Programme of China: [Grant Number 2021YFC0863300]; Beijing Municipal Science and Technology Project: [Grant Number Z211100002521018].