The susceptibility of circulating SARS-CoV-2 variants to neutralization

To the editor:

The emergence of two variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – B.1.1.7 in the United Kingdom and B.1.351 in South Africa – has raised concerns that these variants may escape immunity as a result of the previous infection or vaccination. In an effort to measure the resistance of these variants to neutralization caused by infection or vaccination, we have SARS-CoV-2 pseudoviruses based on the peak protein of the Wuhan-1 reference strain (wild-type), the recombinant vesicular stomatitis virus based. D614G mutation, and the B.1.1.7 and B.1.351 variants. (Details regarding the recombination process are available in the Supplementary Appendix, available in full text of this letter, at NEJM.org.)

Figure 1. Figure 1. Neutralization of SARS-CoV-2 Pseudoviruses in Recovery and Vaccine Serum Samples.

Panel A shows the 50% pseudovirus neutralization titer (pVNT₅₀) in recovering serum collected approximately 34 months after SARS-CoV-2 infection from 34 recovered patients and in serum collected from 50 vaccinated patients receiving the BBIBP-CorV or CoronaVac vaccine 2 to 3 weeks after the second dose at received recombinant vesicular stomatitis virus. –Based SARS-CoV-2 pseudovirus with the Wuhan-1 (wild-type) ear protein. Subject diagrams indicate the median and interquartile range (IQR); the mustache represents 1.5 times the IQ. Panel B shows changes in reciprocal serum pVNT₅₀ titer in 34 restorative serum samples against the D614G, B.1.1.7 and B.1.351 variants, compared to wild-type virus. Panels C and D show changes in the reciprocal pVNT₅₀ titer in serum samples obtained from the 25 recipients of the BBIBP CorV vaccine and 25 recipients of the CoronaVac vaccine, respectively, compared to the D614G, B.1.1.7 and B.1.351 variants, compared with wild-type virus . Factor changes in the geometric mean titer and 95% confidence interval (GI) in the pVNT₅₀ titers, compared to those for wild-type virus, are shown below the P values. Only P values ​​of less than 0.05 (which is significant) are shown. Each data point is the average number of duplicate results. In each panel, the horizontal dotted line represents the lower limit of detection of the test (titer, <30); this limit assigned a value of 10 for geometric calculations and was considered seronegative. In all panels, calculations were performed using the two-tailed Kruskal - Wales test after adjustment for the false discovery figure.

We then evaluated the resistance of the pseudovirus to neutralization by means of a recovery serum obtained from 34 patients 5 months after infection with coronavirus disease 2019 (Covid-19) and serum from 50 participants given 2 to 3 weeks after receiving the second dose. got inactivated virus vaccines – BBIBP -CorV (Sinopharm)¹ of CoronaVac (Sinovac)² – developed in China (Table S1 in the Supplementary Annex). We first determined the serum neutralizing antibody titer against wild-type pseudovirus and observed similar geometric mean titers (GMTs) in serum obtained from recovering patients and from vaccinated (Figure 1A), which suggested a low antibody response after dual-dose vaccination induced by BBIBP-CorV or CoronaVac.^1.2 In particular, undetectable neutralization titers were seen in 4 of 34 recovering serum samples, in 6 of 25 BBIBP-CorV serum samples, and in 4 of 25 CoronaVac serum samples.

We then evaluated the neutralizing activity of restorative serum and vaccinated serum against D614G, B.1.1.7 and B.1.351 variants compared to the wild-type pseudovirus. The restorative serum was significantly more effective (by a factor of 2.4; 95% confidence interval [CI], 1.9 to 3.0) in the neutralization of the D614G pseudovirus, had a similar effect to that of the wild-type virus in the neutralization of the B.1.1.7 variant, and was significantly less effective (by a factor of 0.5; 95% AI, 0.4 to 0.7) to neutralize the B.1.351 pseudovirus (Figure 1B). In addition, 9 of 30 restorative serum samples showed complete loss of neutralizing activity at B.1.351. For the BBIBP-CorV vaccine serum samples, although the GMTs of neutralization against the variants did not differ significantly from the GMT against the wild-type virus, 20 serum samples showed complete or partial loss of neutralization at B.1.351 (Figure 1C). For the CoronaVac vaccine serum samples, we observed a clear decrease in the GMTs in the serum neutralization of B.1.1.7 (by a factor of 0.5; 95% AI, 0.3 to 0.7) and B.1.351 (by a factor of 0.3; 95% BI, 0.2 to 0.4). In addition, most of the serum samples showed the loss of neutralization in full or in part by B.1.351 (Figure 1D).

Our findings indicate that B.1.1.7 showed little resistance to the neutralizing activity of repaired or vaccinated serum, while B.1.351 showed more resistance to the neutralizing of both restorative serum (by a factor of 2) and the which of the vaccinated (by a factor) 2.5 to 3.3) as the wild-type virus. Most of the integrated serum samples tested lost the neutralizing activity, a finding consistent with the results of other recent studies on neutralizing serum or serum obtained from messenger RNA or BBIBP-CorV vaccine recipients.^3-5 Our findings also emphasize the importance of continuous viral monitoring and evaluation of the protective efficacy of vaccines in areas where variants are circulating.

Guo-Lin Wang, Ph.D.
Beijing Institute of Microbiology and Epidemiology, Beijing, China

Zhuang-Ye Wang, B.Med.
Dezhou Center for Disease Control and Prevention, Dezhou, China

Li-Jun Duan, B.Sc.
Beijing Institute of Microbiology and Epidemiology, Beijing, China

Qing-Chuan Meng, B.Med.
Ningjin County Community Health Center, Dezhou, China

Ming-Dong Jiang, M.Med.
Jing Cao, M.Med.
Dezhou Center for Disease Control and Prevention, Dezhou, China

Lin Yao, B.Med.
Ka-Li Zhu, B.Med.
Wu-Chun Cao, Ph.D.
Mai-Juan Ma, Ph.D.
Beijing Institute of Microbiology and Epidemiology, Beijing, China
[email protected], [email protected]

This letter was published on April 6, 2021 on NEJM.org.