Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents

Hao Wang, Yu Yuan, Bihao Wu, Mingzhong Xiao, Zhen Wang, Tingyue Diao, Rui Zeng, Li Chen, Yanshou Lei, Pinpin Long, Yi Guo, Xuefeng Lai, Yuying Wen, Wenhui Li, Hao Cai, Lulu Song, Wei Ni, Youyun Zhao, Kani Ouyang, Jingzhi Wang, Qi Wang, Li Liu, Chaolong Wang, An Pan, Xiaodong Li, Rui Gong, Tangchun Wu

PDF(3286 KB)
PDF(3286 KB)
Front. Med. ›› 2023, Vol. 17 ›› Issue (4) : 747-757. DOI: 10.1007/s11684-022-0954-x
RESEARCH ARTICLE

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents

Author information +
History +

Abstract

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Keywords

COVID-19 convalescent / SARS-CoV-2 / inactivated vaccination / neutralizing antibody / B cell response

Cite this article

Download citation ▾
Hao Wang, Yu Yuan, Bihao Wu, Mingzhong Xiao, Zhen Wang, Tingyue Diao, Rui Zeng, Li Chen, Yanshou Lei, Pinpin Long, Yi Guo, Xuefeng Lai, Yuying Wen, Wenhui Li, Hao Cai, Lulu Song, Wei Ni, Youyun Zhao, Kani Ouyang, Jingzhi Wang, Qi Wang, Li Liu, Chaolong Wang, An Pan, Xiaodong Li, Rui Gong, Tangchun Wu. Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents. Front. Med., 2023, 17(4): 747‒757 https://doi.org/10.1007/s11684-022-0954-x

References

[1]
Cohen JI, Burbelo PD. Reinfection with SARS-CoV-2: implications for vaccines. Clin Infect Dis 2021; 73(11): e4223–e4228
CrossRef Pubmed Google scholar
[2]
Mallapaty S. China’s COVID vaccines have been crucial—now immunity is waning. Nature 2021; 598(7881): 398–399
CrossRef Pubmed Google scholar
[3]
Carreño JM, Alshammary H, Tcheou J, Singh G, Raskin AJ, Kawabata H, Sominsky LA, Clark JJ, Adelsberg DC, Bielak DA, Gonzalez-Reiche AS, Dambrauskas N, Vigdorovich V; PSP-PARIS Study Group, Srivastava K, Sather DN, Sordillo EM, Bajic G, van Bakel H, Simon V, Krammer F. Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature 2022; 602(7898): 682–688
CrossRef Pubmed Google scholar
[4]
Garcia-Beltran WF, St Denis KJ, Hoelzemer A, Lam EC, Nitido AD, Sheehan ML, Berrios C, Ofoman O, Chang CC, Hauser BM, Feldman J, Roederer AL, Gregory DJ, Poznansky MC, Schmidt AG, Iafrate AJ, Naranbhai V, Balazs AB. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell 2022; 185(3): 457–466.e4
CrossRef Pubmed Google scholar
[5]
Goel RR, Apostolidis SA, Painter MM, Mathew D, Pattekar A, Kuthuru O, Gouma S, Hicks P, Meng W, Rosenfeld AM, Dysinger S, Lundgreen KA, Kuri-Cervantes L, Adamski S, Hicks A, Korte S, Oldridge DA, Baxter AE, Giles JR, Weirick ME, McAllister CM, Dougherty J, Long S, D’Andrea K, Hamilton JT, Betts MR, Luning Prak ET, Bates P, Hensley SE, Greenplate AR, Wherry EJ. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination. Sci Immunol 2021; 6(58): eabi6950
CrossRef Pubmed Google scholar
[6]
Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J, Bolland WH, Porrot F, Staropoli I, Lemoine F, Péré H, Veyer D, Puech J, Rodary J, Baele G, Dellicour S, Raymenants J, Gorissen S, Geenen C, Vanmechelen B, Wawina-Bokalanga T, Martí-Carreras J, Cuypers L, Sève A, Hocqueloux L, Prazuck T, Rey FA, Simon-Loriere E, Bruel T, Mouquet H, André E, Schwartz O. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 2022; 602(7898): 671–675
CrossRef Pubmed Google scholar
[7]
Rössler A, Riepler L, Bante D, von Laer D, Kimpel J. SARS-CoV-2 Omicron variant neutralization in serum from vaccinated and convalescent persons. N Engl J Med 2022; 386(7): 698–700
CrossRef Pubmed Google scholar
[8]
Sokal A, Barba-Spaeth G, Fernández I, Broketa M, Azzaoui I, de La Selle A, Vandenberghe A, Fourati S, Roeser A, Meola A, Bouvier-Alias M, Crickx E, Languille L, Michel M, Godeau B, Gallien S, Melica G, Nguyen Y, Zarrouk V, Canoui-Poitrine F, Pirenne F, Mégret J, Pawlotsky JM, Fillatreau S, Bruhns P, Rey FA, Weill JC, Reynaud CA, Chappert P, Mahévas M. mRNA vaccination of naïve and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Immunity 2021; 54(12): 2893–2907.e5
CrossRef Pubmed Google scholar
[9]
Cheng SMS, Mok CKP, Leung YWY, Ng SS, Chan KCK, Ko FW, Chen C, Yiu K, Lam BHS, Lau EHY, Chan KKP, Luk LLH, Li JKC, Tsang LCH, Poon LLM, Hui DSC, Peiris M. Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination. Nat Med 2022; 28(3): 486–489
CrossRef Pubmed Google scholar
[10]
Muena NA, Garcia-Salum T, Pardo-Roa C, Serrano EF, Levican J, Avendano MJ, Almonacid LI, Valenzuela G, Poblete E, Strohmeier S, Salinas E, Haslwanter D, Dieterle ME, Jangra RK, Chandran K, González C, Riquelme A, Krammer F, Tischler ND, Medina RA. Long-lasting neutralizing antibody responses in SARS-CoV-2 seropositive individuals are robustly boosted by immunization with the CoronaVac and BNT162b2 vaccines. eBioMedicine 2022; 78: 103972
CrossRef Google scholar
[11]
Pérez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, Vogels CBF, Malik AA, De la Cruz E, Jorge A, De Los Santos M, Leon P, Breban MI, Billig K, Yildirim I, Pearson C, Downing R, Gagnon E, Muyombwe A, Razeq J, Campbell M, Ko AI, Omer SB, Grubaugh ND, Vermund SH, Iwasaki A. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat Med 2022; 28(3): 481–485
CrossRef Pubmed Google scholar
[12]
Heriyanto RS, Kurniawan A, Wijovi F, Halim DA, Jodhinata C, Marcella E, Susanto B, Wibowo J, Indrawan M, Heryadi NK, Imanuelly M, Anurantha JJ, Hariyanto TI, Marcellin C, Sinaga TD, Rizki SA, Sieto N, Siregar JI, Lugito NPH. The role of COVID-19 survivor status and gender towards neutralizing antibody titers 1, 2, 3 months after Sinovac vaccine administration on clinical-year medical students in Indonesia. Int J Infect Dis 2021; 113: 336–338
CrossRef Pubmed Google scholar
[13]
Ma C, Chen X, Mei F, Xiong Q, Liu Q, Dong L, Liu C, Zou W, Zhan F, Hu B, Liu Y, Liu F, Zhou L, Xu J, Jiang Y, Xu K, Cai K, Chen Y, Yan H, Lan K. Drastic decline in sera neutralization against SARS-CoV-2 Omicron variant in Wuhan COVID-19 convalescents. Emerg Microbes Infect 2022; 11(1): 567–572
CrossRef Pubmed Google scholar
[14]
Yalçın TY, Topçu DI, DoğanÖ, Aydın S, Sarı N, ErolÇ, Kuloğlu ZE, AzapÖK, Can F, Arslan H. Immunogenicity after two doses of inactivated virus vaccine in healthcare workers with and without previous COVID-19 infection: prospective observational study. J Med Virol 2022; 94(1): 279–286
CrossRef Pubmed Google scholar
[15]
Ciabattini A, Pastore G, Fiorino F, Polvere J, Lucchesi S, Pettini E, Auddino S, Rancan I, Durante M, Miscia M, Rossetti B, Fabbiani M, Montagnani F, Medaglini D. Evidence of SARS-CoV-2-specific memory B cells six months after vaccination with the BNT162b2 mRNA vaccine. Front Immunol 2021; 12: 740708
CrossRef Pubmed Google scholar
[16]
Sievers BL, Chakraborty S, Xue Y, Gelbart T, Gonzalez JC, Cassidy AG, Golan Y, Prahl M, Gaw SL, Arunachalam PS, Blish CA, Boyd SD, Davis MM, Jagannathan P, Nadeau KC, Pulendran B, Singh U, Scheuermann RH, Frieman MB, Vashee S, Wang TT, Tan GS. Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses. Sci Transl Med 2022; 14(634): eabn7842
CrossRef Pubmed Google scholar
[17]
Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, Tan W, Wu G, Xu M, Lou Z, Huang W, Xu W, Huang B, Wang H, Wang W, Zhang W, Li N, Xie Z, Ding L, You W, Zhao Y, Yang X, Liu Y, Wang Q, Huang L, Yang Y, Xu G, Luo B, Wang W, Liu P, Guo W, Yang X. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis 2021; 21(1): 39–51
CrossRef Pubmed Google scholar
[18]
Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, Li X, Peng C, Zhang Y, Zhang W, Yang Y, Chen W, Gao X, You W, Wang X, Wang Z, Shi Z, Wang Y, Yang X, Zhang L, Huang L, Wang Q, Lu J, Yang Y, Guo J, Zhou W, Wan X, Wu C, Wang W, Huang S, Du J, Meng Z, Pan A, Yuan Z, Shen S, Guo W, Yang X. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. JAMA 2020; 324(10): 951–960
CrossRef Pubmed Google scholar
[19]
Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, Han W, Chen Z, Tang R, Yin W, Chen X, Hu Y, Liu X, Jiang C, Li J, Yang M, Song Y, Wang X, Gao Q, Zhu F. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021; 21(2): 181–192
CrossRef Pubmed Google scholar
[20]
Sureshchandra S, Lewis SA, Doratt BM, Jankeel A, Coimbra Ibraim I, Messaoudi I. Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine. JCI Insight 2021; 6(24): e153201
CrossRef Pubmed Google scholar
[21]
Liu Y, Zeng Q, Deng C, Li M, Li L, Liu D, Liu M, Ruan X, Mei J, Mo R, Zhou Q, Liu M, Peng S, Wang J, Zhang H, Xiao H. Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine. Cell Discov 2022; 8(1): 10
CrossRef Pubmed Google scholar
[22]
Coppeta L, Ferrari C, Mazza A, Trabucco Aurilio M, Rizza S. Factors associated with pre-vaccination SARS-CoV-2 infection risk among hospital nurses facing COVID-19 outbreak. Int J Environ Res Public Health 2021; 18(24): 13053
CrossRef Pubmed Google scholar
[23]
Rozenfeld Y, Beam J, Maier H, Haggerson W, Boudreau K, Carlson J, Medows R. A model of disparities: risk factors associated with COVID-19 infection. Int J Equity Health 2020; 19(1): 126
CrossRef Pubmed Google scholar
[24]
Cevik M, Baral SD. Networks of SARS-CoV-2 transmission. Science 2021; 373(6551): 162–163
CrossRef Pubmed Google scholar
[25]
Al Kaabi N, Zhang Y, Xia S, Yang Y, Al Qahtani MM, Abdulrazzaq N, Al Nusair M, Hassany M, Jawad JS, Abdalla J, Hussein SE, Al Mazrouei SK, Al Karam M, Li X, Yang X, Wang W, Lai B, Chen W, Huang S, Wang Q, Yang T, Liu Y, Ma R, Hussain ZM, Khan T, Saifuddin Fasihuddin M, You W, Xie Z, Zhao Y, Jiang Z, Zhao G, Zhang Y, Mahmoud S, ElTantawy I, Xiao P, Koshy A, Zaher WA, Wang H, Duan K, Pan A, Yang X. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA 2021; 326(1): 35–45
CrossRef Pubmed Google scholar
[26]
Lumley SF, O’Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB, Marsden BD, Cox S, James T, Warren F, Peck LJ, Ritter TG, de Toledo Z, Warren L, Axten D, Cornall RJ, Jones EY, Stuart DI, Screaton G, Ebner D, Hoosdally S, Chand M, Crook DW, O’Donnell AM, Conlon CP, Pouwels KB, Walker AS, Peto TEA, Hopkins S, Walker TM, Jeffery K, Eyre DW; Oxford University Hospitals Staff Testing Group. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med 2021; 384(6): 533–540
CrossRef Pubmed Google scholar
[27]
Coppeta L, Somma G, Ferrari C, Mazza A, Rizza S, Trabucco Aurilio M, Perrone S, Magrini A, Pietroiusti A. Persistence of anti-S titre among healthcare workers vaccinated with BNT162b2 mRNA COVID-19. Vaccines (Basel) 2021; 9(9): 947
CrossRef Pubmed Google scholar
[28]
Stephens DS, McElrath MJ. COVID-19 and the path to immunity. JAMA 2020; 324(13): 1279–1281
CrossRef Pubmed Google scholar
[29]
Shaman J, Galanti M. Will SARS-CoV-2 become endemic? Science 2020; 370(6516): 527–529 doi:10.1126/science.abe5960
Pubmed
[30]
Chia WN, Zhu F, Ong SWX, Young BE, Fong SW, Le Bert N, Tan CW, Tiu C, Zhang J, Tan SY, Pada S, Chan YH, Tham CYL, Kunasegaran K, Chen MI, Low JGH, Leo YS, Renia L, Bertoletti A, Ng LFP, Lye DC, Wang LF. Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study. Lancet Microbe 2021; 2(6): e240–e249
CrossRef Pubmed Google scholar
[31]
Wang H, Yuan Y, Xiao M, Chen L, Zhao Y, Haiwei Zhang, Long P, Zhou Y, Xu X, Lei Y, Bihao Wu, Diao T, Cai H, Liu L, Shao Z, Wang J, Bai Y, Wang K, Peng M, Liu L, Han S, Mei F, Cai K, Lei Y, Pan A, Wang C, Gong R, Li X, Wu T. Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection. Cell Mol Immunol 2021; 18(7): 1832–1834
CrossRef Pubmed Google scholar
[32]
Coppeta L, Ferrari C, Somma G, Mazza A, D’Ancona U, Marcuccilli F, Grelli S, Aurilio MT, Pietroiusti A, Magrini A, Rizza S. Reduced titers of circulating anti-SARS-CoV-2 antibodies and risk of COVID-19 infection in healthcare workers during the nine months after immunization with the BNT162b2 mRNA vaccine. Vaccines (Basel) 2022; 10(2): 141
CrossRef Pubmed Google scholar
[33]
Hoffmann M, Krüger N, Schulz S, Cossmann A, Rocha C, Kempf A, Nehlmeier I, Graichen L, Moldenhauer AS, Winkler MS, Lier M, Dopfer-Jablonka A, Jäck HM, Behrens GMN, Pöhlmann S. The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic. Cell 2022; 185(3): 447–456.e11
CrossRef Pubmed Google scholar
[34]
Zhang J, Xiao T, Cai Y, Lavine CL, Peng H, Zhu H, Anand K, Tong P, Gautam A, Mayer ML, Walsh RM Jr, Rits-Volloch S, Wesemann DR, Yang W, Seaman MS, Lu J, Chen B. Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant. Science 2021; 374(6573): 1353–1360
CrossRef Pubmed Google scholar
[35]
World Health Organization. Interim recommendations for use of the inactivated COVID-19 vaccine BIBP developed by China National Biotec Group, Sinopharm, 2021
[36]
World Health Organization. Interim recommendations for use of the inactivated COVID-19 vaccine, CoronaVac, developed by Sinovac, 2021
[37]
Laidlaw BJ, Ellebedy AH. The germinal centre B cell response to SARS-CoV-2. Nat Rev Immunol 2022; 22(1): 7–18
CrossRef Pubmed Google scholar
[38]
Wang K, Jia Z, Bao L, Wang L, Cao L, Chi H, Hu Y, Li Q, Zhou Y, Jiang Y, Zhu Q, Deng Y, Liu P, Wang N, Wang L, Liu M, Li Y, Zhu B, Fan K, Fu W, Yang P, Pei X, Cui Z, Qin L, Ge P, Wu J, Liu S, Chen Y, Huang W, Wang Q, Qin CF, Wang Y, Qin C, Wang X. Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants. Nature 2022; 603(7903): 919–925
CrossRef Pubmed Google scholar

Acknowledgements

We thank all the study participants and project staff. This work was supported by the Emergency Key Program of Guangzhou Laboratory (No. EKPG21-30), the Fundamental Research Funds for the Central Universities (No. 2019kfyXMBZ015), the Fellowship of China Postdoctoral Science Foundation (Nos. 2020T130034ZX and 2020M680102), and the National Natural Science Foundation of China (Nos. 72061137006 and 82204113).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-022-0954-x and is accessible for authorized users.

Compliance with ethics guidelines

Hao Wang, Yu Yuan, Bihao Wu, Mingzhong Xiao, Zhen Wang, Tingyue Diao, Rui Zeng, Li Chen, Yanshou Lei, Pinpin Long, Yi Guo, Xuefeng Lai, Yuying Wen, Wenhui Li, Hao Cai, Wei Ni, Youyun Zhao, Kani Ouyang, Jingzhi Wang, Qi Wang, Li Liu, Chaolong Wang, An Pan, Xiaodong Li, Rui Gong, and Tangchun Wu declare that they have no conflict of interest. This study was approved by the Ethics Committee of the School of Public Health, Tongji Medical College, Huazhong University of Science and Technology. Written informed consent was obtained from each participant.

RIGHTS & PERMISSIONS

2022 Higher Education Press
AI Summary AI Mindmap
PDF(3286 KB)

Accesses

Citations

Detail

Sections
Recommended

/