antibody neutralization to sars cov 2 and variants after one year in wuhan CORD-Papers-2021-10-25 (Version 1)

Title: Antibody neutralization to SARS-CoV-2 and variants after one year in Wuhan
Abstract: Most COVID-19 patients can build effective humoral immunity against SARS-CoV-2 after recovery . However, it remains unknown how long the protection can maintain and how efficiently it can protect people from the reinfection of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin G (IgG) maintains at a high level and potently neutralizes the infection of the original strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of the convalescents' sera. Encouragingly, we found that a small fraction of patients' sera showed broad neutralization potency to multiple variants and mutants, suggesting the existence of broadly neutralizing antibodies recognizing the epitopes beyond the mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness relies more on the timely re-administration of the epitope-updated vaccine than the durability of the neutralizing antibodies.
Published: 6/21/2021
DOI: 10.1101/2021.06.16.21258673
DOI_URL: http://doi.org/10.1101/2021.06.16.21258673
Author Name: Liu, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_q
Author Name: Xiong, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xiong_q
Author Name: Mei, F
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mei_f
Author Name: Ma, C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ma_c
Author Name: Zhang, Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhang_z
Author Name: Hu, B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hu_b
Author Name: Xu, J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xu_j
Author Name: Jiang, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jiang_y
Author Name: Zhan, F
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhan_f
Author Name: Chen, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/chen_x
Author Name: Guo, M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/guo_m
Author Name: Wang, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_x
Author Name: Fang, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/fang_y
Author Name: Shen, S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/shen_s
Author Name: Liu, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Liu, F
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_f
Author Name: Zhou, L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhou_l
Author Name: Xu, K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xu_k
Author Name: Ke, C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ke_c
Author Name: Deng, F
Author link: https://covid19-data.nist.gov/pid/rest/local/author/deng_f
Author Name: Cai, K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cai_k
Author Name: Yan, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yan_h
Author Name: Chen, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/chen_y
Author Name: Lan, K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lan_k
sha: eb56320be03a92c3e85daae80c66a9c7a203b25d
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: http://medrxiv.org/cgi/content/short/2021.06.16.21258673v1?rss=1 https://doi.org/10.1101/2021.06.16.21258673
has_full_text: TRUE
Keywords Extracted from Text Content: IgG Wuhan WT patients convalescents' sera COVID-19 sera people SARS-CoV-2 SARS-CoV-2 immunoglobulin 22 G B.1.1.7 COVID-19 patients pseudovirus SARS-CoV-2 nucleocapsid Fig. 2 BHK-21-hACE2 medRxiv preprint Wuhan B.1.525 Wuhan VSV-dG-Luc E484 COVID-19 convalescents SARS-CoV-2 BHK-21 cell line WT-D614G OD450=0.31 SARS-CoV-2 antibody replication-deficient VSV pseudotyping system 88 hACE2 Fig. 1f Fig.1c-d medRxiv preprint anti-SARS-CoV-2 IgM effect(12 people's sera medRxiv B.1.351 (Fig. 2b anti-SARS-CoV-2 Fig. 1A people ACE2 SARS-CoV-2 172 Fig.1a-b Fig. 1a-e IgG samples 321 https://doi.org/10.1101/2021.06.16.21258673 doi patients sera SARS-CoV-2 pseudovirus 87 medRxiv https://doi.org/10.1101/2021.06.16.21258673 doi permission.(which medRxiv preprint Competing interests 347
Extracted Text Content in Record: First 5000 Characters:Most COVID-19 patients can build effective humoral immunity against 17 SARS-CoV-2 after recovery(1, 2). However, it remains unknown how long the 18 protection can maintain and how efficiently it can protect people from the reinfection 19 of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 20 COVID-19 convalescents around one year post-infection in Wuhan, the earliest 21 epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin 22 G (IgG) maintains at a high level and potently neutralizes the infection of the original 23 strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying 24 degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and 25 especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, 26 E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of 27 the convalescents' sera. Encouragingly, we found that a small fraction of patients' sera 28 showed broad neutralization potency to multiple variants and mutants, suggesting the 29 existence of broadly neutralizing antibodies recognizing the epitopes beyond the 30 All rights reserved. No reuse allowed without permission. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness 31 relies more on the timely re-administration of the epitope-updated vaccine than the 32 durability of the neutralizing antibodies. 33 34 Main 35 The SARS-CoV-2 emerged more than a year ago rapidly swept across the world 36 and developed into a long-lasting COVID-19 pandemic with devastating impacts (3, 4) . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 21, 2021. ; https://doi.org/10.1101/2021.06.16.21258673 doi: medRxiv preprint Wuhan is the first known epicenter of the SARS-CoV-2 outbreak. Almost all 53 patients in this city were infected by the original strain before the city reopen and the 54 epidemic here had been well controlled thereafter before the emergence of 55 variants(14). In this study, sera from convalescents infected around one year ago in 56 Wuhan were collected to investigate the SARS-CoV-2 antibody durability and the (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (5/248) tested positive for anti-SARS-CoV-2 IgM (Table S1 ). Conventional ELISA 76 assays were then conducted to determine the anti-RBD IgG level and the competitive 77 ability of ACE2 to RBD-binding of the sera. As we set OD450=0.31 (the mean 78 OD450 value + 3 SD of uninfected people's sera) as the cut-off value, 91 % (225/248) 79 tested positive for anti-SARS-CoV-2-RBD IgG (Fig. 1A) . Our results also showed 80 that the competitive ability is highly consistent with the anti-RBD IgG level ( Fig. 81 1A-E, Table S1), indicating most RBD-targeting antibodies in the patients can 82 interfere with the interaction between ACE2 and RBD. However, the anti-RBD IgG 83 level and the neutralizing activity of the sera showed no statistically significant 84 difference in patients with different severity (Fig.1a-b) , gender ( Fig.1c-d) , and age 85 (Fig. 1e) . 86 The neutralizing activities of the sera were tested with SARS-CoV-2 pseudovirus 87 (WT-D614G) produced based on a replication-deficient VSV pseudotyping system 88 (VSV-dG-Luc) and a BHK-21 cell line stably expressing hACE2 (BHK-21-hACE2). (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 21, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. one mutation (N501Y) in the RBD region, a mutation without prominent immune 122 escape effect(12, 16) (Fig. 2e) . These results showed that the immune escape ability 123 of the variants can be largely attributed to the mutations in the RBD region. among the variants of concern, especially mutations on E484 and K417. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. showing high, medium, and low neutralizing activities in Fig. 1f , respectively. The 141 SARS-CoV-2 nucleocapsid (N) protein immunofluorescence assay showed consistent 142 results with the pseudovirus neutralization assay (Fig. 3a) . 143 We further verified the neutralizing activity of two groups of patients in Fig. 2 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version
PDF JSON Files: document_parses/pdf_json/eb56320be03a92c3e85daae80c66a9c7a203b25d.json
G_ID: antibody_neutralization_to_sars_cov_2_and_variants_after_one_year_in_wuhan
S2 ID: 235486787