Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a major impact on global human health. During the spread of SARS-CoV-2, weakened host immunity and the use of vaccines with low efficacy may result in the development of more-virulent strains or strains with resistance to existing vaccines and antibodies. The prevalence of SARS-CoV-2 mutant strains differs between regions, and this variation may have an impact on the effectiveness of vaccines. In this study, an epidemiological investigation of SARS-CoV-2 in Portugal was performed, and the VSV-ΔG-G* pseudovirus system was used to construct 12 spike protein epidemic mutants, D614G, A222V+D614G, B.1.1.7, S477N+D614G, P1162R+D614G+A222V, D839Y+D614G, L176F+D614G, B.1.1.7+L216F, B.1.1.7+M740V, B.1.258, B.1.258+L1063F, and B.1.258+N751Y. The mutant pseudoviruses were used to infect four susceptible cell lines (Huh7, hACE2-293T-293T, Vero, and LLC-MK2) and 14 cell lines overexpressing ACE2 from different species. Mutant strains did not show increased infectivity or cross-species transmission. Neutralization activity against these pseudoviruses was evaluated using mouse serum and 11 monoclonal antibodies. The neutralizing activity of immunized mouse serum was not significantly reduced with the mutant strains, but the mutant strains from Portugal could evade nine of the 11 monoclonal antibodies tested. Neutralization resistance was mainly caused by the mutations S477N, N439K, and N501Y in the spike-receptor binding domain. These findings emphasize the importance of SARS-CoV-2 mutation tracking in different regions for epidemic prevention and control.
Highlights
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, multiple virus variants have emerged that differ from the original virus by mutations in Handling Editor: John Ziebuhr.1 3 Vol.:(0123456789)further understand the biological activity of SARS-CoV-2 epidemic strains in Portugal, we used a pseudovirus system with a vesicular stomatitis virus (VSV) vector to simulate the circulating viruses and analyzed the effect of mutations on transmission, infectivity, and antigenicity.research protocol was approved by the Animal Welfare Ethical Review Committee of the National Institute of Food and Drug Control.Plasmid construction
Among the mutant strains that appeared in Portugal in December, UK strain B.1.1.7 accounted for 73.1%; this strain possessed the L216F and M740V double mutation
We found that the UK epidemic strain B.1.1.7 and its variants can escape monoclonal antibodies (mAbs) 03-1F9, 2H10, approximately 0.03–0.18 μg/mL) and showed no significant differences (P > 0.05)
Summary
Further understand the biological activity of SARS-CoV-2 epidemic strains in Portugal, we used a pseudovirus system with a vesicular stomatitis virus (VSV) vector to simulate the circulating viruses and analyzed the effect of mutations on transmission, infectivity, and antigenicity.
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