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

BBIBP-CorV and ZF2001 are two COVID-19 vaccines developed in China. BBIBP-CorV is an inactivated virus vaccine approved for conditional marketing authorisation 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.2, 3 Both vaccines showed good immunogenicity in phase 1 and 2 trials.1, 3

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. This variant was first isolated in China on Jan 25, 2021, 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) (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).