1. Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2. CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China 3. University of Chinese Academy of Sciences, Beijing 100049, China 4. Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan 430061, China 5. Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China
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.
JM Carreño, H Alshammary, J Tcheou, G Singh, AJ Raskin, H Kawabata, LA Sominsky, JJ Clark, DC Adelsberg, DA Bielak, AS Gonzalez-Reiche, N Dambrauskas, V; PSP-PARIS Study Group Vigdorovich, K Srivastava, DN Sather, EM Sordillo, G Bajic, Bakel H van, V Simon, F Krammer. Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature 2022; 602(7898): 682–688 https://doi.org/10.1038/s41586-022-04399-5
pmid: 35016197
4
WF Garcia-Beltran, KJ St Denis, A Hoelzemer, EC Lam, AD Nitido, ML Sheehan, C Berrios, O Ofoman, CC Chang, BM Hauser, J Feldman, AL Roederer, DJ Gregory, MC Poznansky, AG Schmidt, AJ Iafrate, V Naranbhai, AB Balazs. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell 2022; 185(3): 457–466.e4 https://doi.org/10.1016/j.cell.2021.12.033
pmid: 34995482
5
RR Goel, SA Apostolidis, MM Painter, D Mathew, A Pattekar, O Kuthuru, S Gouma, P Hicks, W Meng, AM Rosenfeld, S Dysinger, KA Lundgreen, L Kuri-Cervantes, S Adamski, A Hicks, S Korte, DA Oldridge, AE Baxter, JR Giles, ME Weirick, CM McAllister, J Dougherty, S Long, K D’Andrea, JT Hamilton, MR Betts, Prak ET Luning, P Bates, SE Hensley, AR Greenplate, EJ Wherry. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination. Sci Immunol 2021; 6(58): eabi6950 https://doi.org/10.1126/sciimmunol.abi6950
pmid: 33858945
6
D Planas, N Saunders, P Maes, F Guivel-Benhassine, C Planchais, J Buchrieser, WH Bolland, F Porrot, I Staropoli, F Lemoine, H Péré, D Veyer, J Puech, J Rodary, G Baele, S Dellicour, J Raymenants, S Gorissen, C Geenen, B Vanmechelen, T Wawina-Bokalanga, J Martí-Carreras, L Cuypers, A Sève, L Hocqueloux, T Prazuck, FA Rey, E Simon-Loriere, T Bruel, H Mouquet, E André, O Schwartz. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 2022; 602(7898): 671–675 https://doi.org/10.1038/s41586-021-04389-z
pmid: 35016199
7
A Rössler, L Riepler, D Bante, Laer D von, J Kimpel. SARS-CoV-2 Omicron variant neutralization in serum from vaccinated and convalescent persons. N Engl J Med 2022; 386(7): 698–700 https://doi.org/10.1056/NEJMc2119236
pmid: 35021005
8
A Sokal, G Barba-Spaeth, I Fernández, M Broketa, I Azzaoui, La Selle A de, A Vandenberghe, S Fourati, A Roeser, A Meola, M Bouvier-Alias, E Crickx, L Languille, M Michel, B Godeau, S Gallien, G Melica, Y Nguyen, V Zarrouk, F Canoui-Poitrine, F Pirenne, J Mégret, JM Pawlotsky, S Fillatreau, P Bruhns, FA Rey, JC Weill, CA Reynaud, P Chappert, M Mahévas. 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 https://doi.org/10.1016/j.immuni.2021.09.011
pmid: 34614412
9
SMS Cheng, CKP Mok, YWY Leung, SS Ng, KCK Chan, FW Ko, C Chen, K Yiu, BHS Lam, EHY Lau, KKP Chan, LLH Luk, JKC Li, LCH Tsang, LLM Poon, DSC Hui, M Peiris. 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 https://doi.org/10.1038/s41591-022-01704-7
pmid: 35051989
10
NA Muena, T Garcia-Salum, C Pardo-Roa, EF Serrano, J Levican, MJ Avendano, LI Almonacid, G Valenzuela, E Poblete, S Strohmeier, E Salinas, D Haslwanter, ME Dieterle, RK Jangra, K Chandran, C González, A Riquelme, F Krammer, ND Tischler, RA Medina. 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 https://doi.org/10.1101/2021.05.17.21257197
11
E Pérez-Then, C Lucas, VS Monteiro, M Miric, V Brache, L Cochon, CBF Vogels, AA Malik, la Cruz E De, A Jorge, Los Santos M De, P Leon, MI Breban, K Billig, I Yildirim, C Pearson, R Downing, E Gagnon, A Muyombwe, J Razeq, M Campbell, AI Ko, SB Omer, ND Grubaugh, SH Vermund, A Iwasaki. 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 https://doi.org/10.1038/s41591-022-01705-6
pmid: 35051990
12
RS Heriyanto, A Kurniawan, F Wijovi, DA Halim, C Jodhinata, E Marcella, B Susanto, J Wibowo, M Indrawan, NK Heryadi, M Imanuelly, JJ Anurantha, TI Hariyanto, C Marcellin, TD Sinaga, SA Rizki, N Sieto, JI Siregar, NPH Lugito. 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 https://doi.org/10.1016/j.ijid.2021.10.009
pmid: 34653654
13
C Ma, X Chen, F Mei, Q Xiong, Q Liu, L Dong, C Liu, W Zou, F Zhan, B Hu, Y Liu, F Liu, L Zhou, J Xu, Y Jiang, K Xu, K Cai, Y Chen, H Yan, K Lan. Drastic decline in sera neutralization against SARS-CoV-2 Omicron variant in Wuhan COVID-19 convalescents. Emerg Microbes Infect 2022; 11(1): 567–572 https://doi.org/10.1080/22221751.2022.2031311
pmid: 35060426
14
TY Yalçın, DI Topçu, Ö Doğan, S Aydın, N Sarı, Ç Erol, ZE Kuloğlu, ÖK Azap, F Can, H Arslan. 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 https://doi.org/10.1002/jmv.27316
pmid: 34468990
15
A Ciabattini, G Pastore, F Fiorino, J Polvere, S Lucchesi, E Pettini, S Auddino, I Rancan, M Durante, M Miscia, B Rossetti, M Fabbiani, F Montagnani, D Medaglini. Evidence of SARS-CoV-2-specific memory B cells six months after vaccination with the BNT162b2 mRNA vaccine. Front Immunol 2021; 12: 740708 https://doi.org/10.3389/fimmu.2021.740708
pmid: 34650563
16
BL Sievers, S Chakraborty, Y Xue, T Gelbart, JC Gonzalez, AG Cassidy, Y Golan, M Prahl, SL Gaw, PS Arunachalam, CA Blish, SD Boyd, MM Davis, P Jagannathan, KC Nadeau, B Pulendran, U Singh, RH Scheuermann, MB Frieman, S Vashee, TT Wang, GS Tan. 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 https://doi.org/10.1126/scitranslmed.abn7842
pmid: 35025672
17
S Xia, Y Zhang, Y Wang, H Wang, Y Yang, GF Gao, W Tan, G Wu, M Xu, Z Lou, W Huang, W Xu, B Huang, H Wang, W Wang, W Zhang, N Li, Z Xie, L Ding, W You, Y Zhao, X Yang, Y Liu, Q Wang, L Huang, Y Yang, G Xu, B Luo, W Wang, P Liu, W Guo, X Yang. 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 https://doi.org/10.1016/S1473-3099(20)30831-8
pmid: 33069281
18
S Xia, K Duan, Y Zhang, D Zhao, H Zhang, Z Xie, X Li, C Peng, Y Zhang, W Zhang, Y Yang, W Chen, X Gao, W You, X Wang, Z Wang, Z Shi, Y Wang, X Yang, L Zhang, L Huang, Q Wang, J Lu, Y Yang, J Guo, W Zhou, X Wan, C Wu, W Wang, S Huang, J Du, Z Meng, A Pan, Z Yuan, S Shen, W Guo, X Yang. 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 https://doi.org/10.1001/jama.2020.15543
pmid: 32789505
19
Y Zhang, G Zeng, H Pan, C Li, Y Hu, K Chu, W Han, Z Chen, R Tang, W Yin, X Chen, Y Hu, X Liu, C Jiang, J Li, M Yang, Y Song, X Wang, Q Gao, F Zhu. 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 https://doi.org/10.1016/S1473-3099(20)30843-4
pmid: 33217362
20
S Sureshchandra, SA Lewis, BM Doratt, A Jankeel, I Coimbra Ibraim, I Messaoudi. Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine. JCI Insight 2021; 6(24): e153201 https://doi.org/10.1172/jci.insight.153201
pmid: 34935643
21
Y Liu, Q Zeng, C Deng, M Li, L Li, D Liu, M Liu, X Ruan, J Mei, R Mo, Q Zhou, M Liu, S Peng, J Wang, H Zhang, H Xiao. 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 https://doi.org/10.1038/s41421-022-00373-7
pmid: 35102140
22
L Coppeta, C Ferrari, A Mazza, M Trabucco Aurilio, S Rizza. 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 https://doi.org/10.3390/ijerph182413053
pmid: 34948662
23
Y Rozenfeld, J Beam, H Maier, W Haggerson, K Boudreau, J Carlson, R Medows. A model of disparities: risk factors associated with COVID-19 infection. Int J Equity Health 2020; 19(1): 126 https://doi.org/10.1186/s12939-020-01242-z
pmid: 32727486
N Al Kaabi, Y Zhang, S Xia, Y Yang, MM Al Qahtani, N Abdulrazzaq, M Al Nusair, M Hassany, JS Jawad, J Abdalla, SE Hussein, SK Al Mazrouei, M Al Karam, X Li, X Yang, W Wang, B Lai, W Chen, S Huang, Q Wang, T Yang, Y Liu, R Ma, ZM Hussain, T Khan, M Saifuddin Fasihuddin, W You, Z Xie, Y Zhao, Z Jiang, G Zhao, Y Zhang, S Mahmoud, I ElTantawy, P Xiao, A Koshy, WA Zaher, H Wang, K Duan, A Pan, X Yang. 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 https://doi.org/10.1001/jama.2021.8565
pmid: 34037666
26
SF Lumley, D O’Donnell, NE Stoesser, PC Matthews, A Howarth, SB Hatch, BD Marsden, S Cox, T James, F Warren, LJ Peck, TG Ritter, Toledo Z de, L Warren, D Axten, RJ Cornall, EY Jones, DI Stuart, G Screaton, D Ebner, S Hoosdally, M Chand, DW Crook, AM O’Donnell, CP Conlon, KB Pouwels, AS Walker, TEA Peto, S Hopkins, TM Walker, K Jeffery, DW; Oxford University Hospitals Staff Testing Group Eyre. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med 2021; 384(6): 533–540 https://doi.org/10.1056/NEJMoa2034545
pmid: 33369366
27
L Coppeta, G Somma, C Ferrari, A Mazza, S Rizza, M Trabucco Aurilio, S Perrone, A Magrini, A Pietroiusti. Persistence of anti-S titre among healthcare workers vaccinated with BNT162b2 mRNA COVID-19. Vaccines (Basel) 2021; 9(9): 947 https://doi.org/10.3390/vaccines9090947
pmid: 34579184
Shaman J, Galanti M. Will SARS-CoV-2 become endemic? Science 2020; 370(6516): 527–529 doi:10.1126/science.abe5960
pmid: 33055131
30
WN Chia, F Zhu, SWX Ong, BE Young, SW Fong, N Le Bert, CW Tan, C Tiu, J Zhang, SY Tan, S Pada, YH Chan, CYL Tham, K Kunasegaran, MI Chen, JGH Low, YS Leo, L Renia, A Bertoletti, LFP Ng, DC Lye, LF Wang. Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study. Lancet Microbe 2021; 2(6): e240–e249 https://doi.org/10.1016/S2666-5247(21)00025-2
pmid: 33778792
31
H Wang, Y Yuan, M Xiao, L Chen, Y Zhao, Zhang Haiwei, P Long, Y Zhou, X Xu, Y Lei, Wu Bihao, T Diao, H Cai, L Liu, Z Shao, J Wang, Y Bai, K Wang, M Peng, L Liu, S Han, F Mei, K Cai, Y Lei, A Pan, C Wang, R Gong, X Li, T Wu. Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection. Cell Mol Immunol 2021; 18(7): 1832–1834 https://doi.org/10.1038/s41423-021-00708-6
pmid: 34099890
32
L Coppeta, C Ferrari, G Somma, A Mazza, U D’Ancona, F Marcuccilli, S Grelli, MT Aurilio, A Pietroiusti, A Magrini, S Rizza. 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 https://doi.org/10.3390/vaccines10020141
pmid: 35214600
33
M Hoffmann, N Krüger, S Schulz, A Cossmann, C Rocha, A Kempf, I Nehlmeier, L Graichen, AS Moldenhauer, MS Winkler, M Lier, A Dopfer-Jablonka, HM Jäck, GMN Behrens, S Pöhlmann. 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 https://doi.org/10.1016/j.cell.2021.12.032
pmid: 35026151
34
J Zhang, T Xiao, Y Cai, CL Lavine, H Peng, H Zhu, K Anand, P Tong, A Gautam, ML Mayer, RM Jr Walsh, S Rits-Volloch, DR Wesemann, W Yang, MS Seaman, J Lu, B Chen. Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant. Science 2021; 374(6573): 1353–1360 https://doi.org/10.1126/science.abl9463
pmid: 34698504
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
K Wang, Z Jia, L Bao, L Wang, L Cao, H Chi, Y Hu, Q Li, Y Zhou, Y Jiang, Q Zhu, Y Deng, P Liu, N Wang, L Wang, M Liu, Y Li, B Zhu, K Fan, W Fu, P Yang, X Pei, Z Cui, L Qin, P Ge, J Wu, S Liu, Y Chen, W Huang, Q Wang, CF Qin, Y Wang, C Qin, X Wang. Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants. Nature 2022; 603(7903): 919–925 https://doi.org/10.1038/s41586-022-04466-x
pmid: 35090164