Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection

Abstract

The ongoing pandemic of coronavirus disease 19 (COVID-19) is caused by a newly discovered β coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6–7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6–7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6–7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4⁺ and CD8⁺ cells were increased upon SARS-CoV-2 antigen stimulation. Together, these results indicate that durable anti-SARS-CoV-2 immunity is common in convalescent population, and vaccines developed from 614D variant may offer protection from the currently predominant 614D variant of SARS-CoV-2.

Keywords

SARS-CoV-2 / neutralizing antibodies / T-cell response

References

[1] Zhou G, Chen S, Chen Z. Back to the spring of 2020: facts and hope of COVID-19 outbreak. Front Med 2020; 14(2): 113–116

[2] Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies. Front Med 2020; 14(2): 117–125

[3] Zhou M, Zhang X, Qu J. Coronavirus disease 2019 (COVID-19): a clinical update. Front Med 2020; 14(2): 126–135

[4] Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A, Chng MHY, Lin M, Tan N, Linster M, Chia WN, Chen MI, Wang LF, Ooi EE, Kalimuddin S, Tambyah PA, Low JG, Tan YJ, Bertoletti A. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 2020; 584(7821): 457–462

[5] Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, Rawlings SA, Sutherland A, Premkumar L, Jadi RS, Marrama D, de Silva AM, Frazier A, Carlin AF, Greenbaum JA, Peters B, Krammer F, Smith DM, Crotty S, Sette A. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020; 181(7): 1489–1501.e15

[6] To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, Yip CC, Cai JP, Chan JM, Chik TS, Lau DP, Choi CY, Chen LL, Chan WM, Chan KH, Ip JD, Ng AC, Poon RW, Luo CT, Cheng VC, Chan JF, Hung IF, Chen Z, Chen H, Yuen KY. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis 2020; 20(5): 565–574

[7] Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, Agudelo M, Barnes CO, Gazumyan A, Finkin S, Hägglöf T, Oliveira TY, Viant C, Hurley A, Hoffmann HH, Millard KG, Kost RG, Cipolla M, Gordon K, Bianchini F, Chen ST, Ramos V, Patel R, Dizon J, Shimeliovich I, Mendoza P, Hartweger H, Nogueira L, Pack M, Horowitz J, Schmidt F, Weisblum Y, Michailidis E, Ashbrook AW, Waltari E, Pak JE, Huey-Tubman KE, Koranda N, Hoffman PR, West AP Jr, Rice CM, Hatziioannou T, Bjorkman PJ, Bieniasz PD, Caskey M, Nussenzweig MC. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 2020; 584(7821): 437–442

[8] Ibarrondo FJ, Fulcher JA, Goodman-Meza D, Elliott J, Hofmann C, Hausner MA, Ferbas KG, Tobin NH, Aldrovandi GM, Yang OO. Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19. N Engl J Med 2020; 383(11): 1085–1087

[9] Gudbjartsson DF, Norddahl GL, Melsted P, Gunnarsdottir K, Holm H, Eythorsson E, Arnthorsson AO, Helgason D, Bjarnadottir K, Ingvarsson RF, Thorsteinsdottir B, Kristjansdottir S, Birgisdottir K, Kristinsdottir AM, Sigurdsson MI, Arnadottir GA, Ivarsdottir EV, Andresdottir M, Jonsson F, Agustsdottir AB, Berglund J, Eiriksdottir B, Fridriksdottir R, Gardarsdottir EE, Gottfredsson M, Gretarsdottir OS, Gudmundsdottir S, Gudmundsson KR, Gunnarsdottir TR, Gylfason A, Helgason A, Jensson BO, Jonasdottir A, Jonsson H, Kristjansson T, Kristinsson KG, Magnusdottir DN, Magnusson OT, Olafsdottir LB, Rognvaldsson S, le Roux L, Sigmundsdottir G, Sigurdsson A, Sveinbjornsson G, Sveinsdottir KE, Sveinsdottir M, Thorarensen EA, Thorbjornsson B, Thordardottir M, Saemundsdottir J, Kristjansson SH, Josefsdottir KS, Masson G, Georgsson G, Kristjansson M, Moller A, Palsson R, Gudnason T, Thorsteinsdottir U, Jonsdottir I, Sulem P, Stefansson K. Humoral immune response to SARS-CoV-2 in Iceland. N Engl J Med 2020; [Epub ahead of print] doi: 10.1056/NEJMoa2026116

[10] Alter G, Seder R. The power of antibody-based surveillance. N Engl J Med 2020; [Epub ahead of print] doi: 10.1056/NEJMe2028079

[11] Zhang NN, Li XF, Deng YQ, Zhao H, Huang YJ, Yang G, Huang WJ, Gao P, Zhou C, Zhang RR, Guo Y, Sun SH, Fan H, Zu SL, Chen Q, He Q, Cao TS, Huang XY, Qiu HY, Nie JH, Jiang Y, Yan HY, Ye Q, Zhong X, Xue XL, Zha ZY, Zhou D, Yang X, Wang YC, Ying B, Qin CF. A thermostable mRNA vaccine against COVID-19. Cell 2020; 182(5): 1271–1283.e16

[12] Nie J, Li Q, Wu J, Zhao C, Hao H, Liu H, Zhang L, Nie L, Qin H, Wang M, Lu Q, Li X, Sun Q, Liu J, Fan C, Huang W, Xu M, Wang Y. Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Emerg Microbes Infect 2020; 9(1): 680–686

[13] Shi H, Ye J, Teng J, Yin Y, Hu Q, Wu X, Liu H, Cheng X, Su Y, Liu M, Gu J, Lu T, Chen H, Zheng H, Sun Y, Yang C. Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients. Arthritis Res Ther 2017; 19(1): 52

[14] Goudot C, Coillard A, Villani AC, Gueguen P, Cros A, Sarkizova S, Tang-Huau TL, Bohec M, Baulande S, Hacohen N, Amigorena S, Segura E. Aryl hydrocarbon receptor controls monocyte differentiation into dendritic cells versus macrophages. Immunity 2017; 47(3): 582–596.e6

[15] Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, Hengartner N, Giorgi EE, Bhattacharya T, Foley B, Hastie KM, Parker MD, Partridge DG, Evans CM, Freeman TM, de Silva TI, Sheffield C-GG, McDanal C, Perez LG, Tang H, Moon-Walker A, Whelan SP, LaBranche CC, Saphire EO, Montefiori DC. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 2020; 182(4): 812–827.e19

[16] Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, Jia X, Wu M, Shi B, Xu S, Chen J, Wang W, Chen B, Jiang L, Yu S, Lu J, Wang J, Xu M, Yuan Z, Zhang Q, Zhang X, Zhao G, Wang S, Chen S, Lu H. Viral and host factors related to the clinical outcome of COVID-19. Nature 2020; 583(7816): 437–440

[17] Rogers TF, Zhao F, Huang D, Beutler N, Burns A, He WT, Limbo O, Smith C, Song G, Woehl J, Yang L, Abbott RK, Callaghan S, Garcia E, Hurtado J, Parren M, Peng L, Ramirez S, Ricketts J, Ricciardi MJ, Rawlings SA, Wu NC, Yuan M, Smith DM, Nemazee D, Teijaro JR, Voss JE, Wilson IA, Andrabi R, Briney B, Landais E, Sok D, Jardine JG, Burton DR. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 2020; 369(6506): 956–963

[18] Peng H, Yang LT, Li J, Lu ZQ, Wang LY, Koup RA, Bailer RT, Wu CY. Human memory T cell responses to SARS-CoV E protein. Microbes Infect 2006; 8(9-10): 2424–2431

[19] Peng H, Yang LT, Wang LY, Li J, Huang J, Lu ZQ, Koup RA, Bailer RT, Wu CY. Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients. Virology 2006; 351(2): 466–475

[20] Ng OW, Chia A, Tan AT, Jadi RS, Leong HN, Bertoletti A, Tan YJ. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection. Vaccine 2016; 34(17): 2008–2014

[21] Yang L, Peng H, Zhu Z, Li G, Huang Z, Zhao Z, Koup RA, Bailer RT, Wu C. Persistent memory CD4⁺ and CD8⁺ T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen. J Gen Virol 2007; 88(Pt 10): 2740–2748

Acknowledgements

This work was supported by grant from Double First-Class Project (No. WF510162602) from the Ministry of Education, State Key Laboratory of Medical Genomics, Overseas Expertise Introduction Project for Discipline Innovation (111 Project, No. B17029) and National Key R&D Program of China (No. 2019YFA0905902), the Shanghai Guangci Translational Medical Research Development Foundation.

Compliance with ethics guidelines

Yun Tan, Feng Liu, Xiaoguang Xu, Yun Ling, Weijin Huang, Zhaoqin Zhu, Mingquan Guo, Yixiao Lin, Ziyu Fu, Dongguo Liang, Tengfei Zhang, Jian Fan, Miao Xu, Hongzhou Lu, and Saijuan Chen declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

RIGHTS & PERMISSIONS

2020 Higher Education Press