Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2

Peng, Qiaoli1,2,3,4; Zhou, Runhong1,4,5; Liu, Na6; Wang, Hui2,3; Xu, Haoran1,4; Zhao, Meiqing1,4; Yang, Dawei1,4; Au, Ka-Kit1,4; Huang, Haode1,4; Liu, Li1,4,5; Chen, Zhiwei1,4,5,6,7

2022-10-01

10.1038/s41423-022-00924-8

Cellular & Molecular Immunology   Impact Factor & Quartile

1672-7681

2042-0226

Mutations in SARS-CoV-2 variants of concern (VOCs) have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies (NAbs). How naturally occurring spike mutations affect the infectivity and antigenicity of VOCs remains to be investigated. The entry efficiency of individual spike mutations was determined in vitro using pseudotyped viruses. BALB/c mice were immunized with 2-dose DNA vaccines encoding B.1.1.7, B.1.351, B.1.1.529 and their single mutations. Cellular and humoral immune responses were then compared to determine the impact of individual mutations on immunogenicity. In the B.1.1.7 lineage, Del69-70 and Del 144 in NTD, A570D and P681H in SD1 and S982A and D1118H in S2 significantly increased viral entry, whereas T716I resulted in a decrease. In the B.1.351 lineage, L18F and Del 242-244 in the NTD, K417N in the RBD and A701V in S2 also increased viral entry. S982A weakened the generation of binding antibodies. All sera showed reduced cross-neutralization activity against B.1.351, B.1.617.2 (Delta) and B.1.1.529 (Omicron BA.1). S982A, L18F, and Del 242-244 hindered the induction of cross-NAbs, whereas Del 69-70, Del144, R246I, and K417N showed the opposite effects. B.1.351 elicited adequate broad cross-NAbs against both B.1.351 and B.1.617.2. All immunogens tested, however, showed low neutralization against circulating B.1.1.529. In addition, T-cell responses were unlikely affected by mutations tested in the spike. We conclude that individual spike mutations influence viral infectivity and vaccine immunogenicity. Designing VOC-targeted vaccines is likely necessary to overcome immune evasion from current vaccines and neutralizing antibodies.

SARS-CoV-2 Variants of Concern Single mutation neutralizing antibody T cell responses vaccine immunogenicity

SCI

English

Others

Hong Kong Research Grants Council Collaborative Research Fund["C7156-20GF","C1134-20GF"] ; Research Grants Council General Research Fund[GRF17117422] ; Hong Kong Health and Medical Research Fund["COVID190123","19181012","COVID1903010","4"] ; Shenzhen Science and Technology Program["JSGG20200225151410198","JCYJ20210324131610027"] ; Theme-Based Research Scheme["T11-706/18-N","T11-709/21-N"]

Immunology

Immunology

WOS:000866292900001

CHIN SOCIETY IMMUNOLOGY

Web of Science

1.Univ Hong Kong, Li Ka Shing Fac Med, AIDS Inst, Hong Kong, Peoples R China
2.Southern Univ Sci & Technol, Natl Clin Res Ctr Infect Dis, HKU AIDS Inst Shenzhen Res Lab, Peoples Hosp Shenzhen 3, Shenzhen, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 2, Shenzhen, Guangdong, Peoples R China
4.Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Hong Kong, Peoples R China
5.Univ Hong Kong, Ctr Virol Vaccinol & Therapeut Ltd, Hong Kong, Peoples R China
6.Univ Hong Kong, HKU AIDS Inst Joint Lab, Dept Clin Microbiol & Infect Control, Shenzhen Hosp, Shenzhen, Guangdong, Peoples R China
7.Univ Hong Kong, State Key Lab Emerging Infect Dis, Hong Kong, Peoples R China

Peng, Qiaoli,Zhou, Runhong,Liu, Na,et al. Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2[J]. Cellular & Molecular Immunology,2022.

Peng, Qiaoli.,Zhou, Runhong.,Liu, Na.,Wang, Hui.,Xu, Haoran.,...&Chen, Zhiwei.(2022).Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2.Cellular & Molecular Immunology.

Peng, Qiaoli,et al."Naturally occurring spike mutations influence the infectivity and immunogenicity of SARS-CoV-2".Cellular & Molecular Immunology (2022).