Serum sample neutralisation of BBIBP-CorV and ZF2001 vaccines to SARS-CoV-2 501Y.V2

Abstract

BBIBP-CorV and ZF2001 are two COVID-19 vaccines developed in China. BBIBP-CorV is an inactivated virus vaccine approved for conditional marketing authorisation1Xia S Zhang Y Wang Y et al.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: 39-51Summary Full Text Full Text PDF PubMed Scopus (788) Google Scholar and ZF2001 is a recombinant dimeric receptor-binding domain (RBD) protein vaccine currently in phase 3 clinical trials and approved for emergency use in China and Uzbekistan.2Dai L Zheng T Xu K et al.A universal design of betacoronavirus vaccines against COVID-19, MERS, and SARS.Cell. 2020; 182: 722-733Summary Full Text Full Text PDF PubMed Scopus (300) Google Scholar, 3Yang S Li Y dai L et al.Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.Lancet Infect Dis. 2021; (published online March 24.)https://doi.org/10.1016/S1473-3099(21)00127-4Summary Full Text Full Text PDF Scopus (267) Google Scholar Both vaccines showed good immunogenicity in phase 1 and 2 trials.1Xia S Zhang Y Wang Y et al.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: 39-51Summary Full Text Full Text PDF PubMed Scopus (788) Google Scholar, 3Yang S Li Y dai L et al.Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.Lancet Infect Dis. 2021; (published online March 24.)https://doi.org/10.1016/S1473-3099(21)00127-4Summary Full Text Full Text PDF Scopus (267) Google Scholar In the past few months, several SARS-CoV-2 variants of concern have been reported, especially the 501Y.V2, which was first isolated in South Africa, raising serious concern about the efficacy of the vaccines under development.4Wu K Werner AP Koch M et al.Serum neutralizing activity elicited by mRNA-1273 vaccine.N Engl J Med. 2021; (published online March 17.)https://doi.org/10.1056/NEJMc2102179Crossref Scopus (277) Google Scholar This variant was first isolated in China on Jan 25, 2021,5Meng J Mei S Chen L et al.Notes from the field: a case of new variant COVID-19 first emerging in South Africa detected in a security guard at the isolation point — Shenzhen, China, January 23, 2021.China CDC Weekly. 2021; 3: 28-29http://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2021.051Date accessed: April 6, 2021Crossref Scopus (5) Google Scholar which contains ten amino acid mutation sites in spike (S) protein with five (Asp80Ala, Leu242del, Ala243del, Leu244del, and Arg246Ile) located at N-terminal domain, three (Lys417Asn, Glu484Lys, and Asn501Tyr) in RBD, and two in C-terminal domain 2 (CTD2) and S1/S2-S2' region (appendix p 2). We assessed neutralisation activity in 24 serum samples from participants in two clinical trials, 12 who had been vaccinated with BBIBP-CorV and 12 who had been vaccinated with ZF2001, who were randomly selected to cover a range of different neutralising titres (appendix p 3). We measured the neutralising activity in these serum samples against live SARS-CoV-2 strains GDPCC (501Y.V2)5Meng J Mei S Chen L et al.Notes from the field: a case of new variant COVID-19 first emerging in South Africa detected in a security guard at the isolation point — Shenzhen, China, January 23, 2021.China CDC Weekly. 2021; 3: 28-29http://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2021.051Date accessed: April 6, 2021Crossref Scopus (5) Google Scholar (appendix p 4). SARS-CoV-2 strains HB02 (wild type) and BJ01 (D614G) were tested as the control. All 24 serum samples from either recipients of BBIBP-CorV or ZF2001 largely preserved neutralisation of the 501Y.V2 variant, with slightly reduced geometric mean titres (GMTs) compared with their titres against the wild type or D614G strains (appendix p 2). For BBIBP-CorV, the GMT decreased from 110·9 (95% CI 76·7–160·2) to 71·5 (51·1–100·1). For ZF2001, this the GMT decreased from 106·1 (95% CI 75·0–150·1) to 66·6 (51·0–86·9). Our findings suggest that the 501Y.V2 variant does not escape the immunity induced by vaccines targeting the whole virus (BBIBP-CorV) or S protein dimeric RBD (ZF2001). The potential 1·5 to 1·6 times reduction in neutralising GMTs should be taken into account for their effect on the clinical efficacy of these vaccines. For both vaccines, immune serum samples neutralise both variant 501Y.V2 and D614G, the variant currently circulating globally, non-significantly (appendix p 2). For ZF2001, a some significance (p=0·04) between variant 501Y.V2 and the wild type might be due to the sample selection and size. The neutralisation-reduction discrepancy between our protein-based vaccine against authentic virus and mRNA vaccine against pseudotyped virus needs further investigation in the future. BH and LD contributed equally. We declare no competing interests. This work was supported by the National Program on Key Research Project of China (2016YFD0500301, 2020YFA0907101), the National Natural Science Foundation of China (82041041, 82061138008), National Mega Projects of China for Major Infectious Diseases (2016ZX10004001-003). LD is supported by Youth Innovation Promotion Association of the CAS (2018113). Download .pdf (.29 MB) Help with pdf files Supplementary appendix Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trialThe inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 μg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 μg dose or 4 μg dose on days 0 and 14. Full-Text PDF Correction to Lancet Microbe 2021; published online April 13. https://doi.org/10.1016/S2666-5247(21)00082-3Huang B, Dai L, Wang H, et al. Serum sample neutralisation of BBIBP-CorV and ZF2001 vaccines to SARS-CoV-2 501Y.V2. Lancet Microbe 2021; published online April 13. https://doi.org/10.1016/S2666-5247(21)00082-3—The title page of the appendix accompanying this correspondence stated that the correspondence and appendix had been peer reviewed. This was incorrect. The cover page of the appendix has been corrected to reflect this as of April 27, 2021 Full-Text PDF Open Access

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