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The sensitivity 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-raises concerns that these variants may escape Any kind of previously developed immune infection or vaccination. In order to measure the resistance of these variants to neutralization caused by infection or vaccination, we generated a SARS-CoV-2 pseudovirus based on recombinant vesicular stomatitis virus, which contains a mutation of the Wuhan-1 reference strain (wild type). Haptoprotein. D61

4G mutation and B.1.1.7 and B.1.351 variants. (For more information on the reorganization process, please see the supplementary appendix. The full text of the letter can be found on NEJM.org.)

Neutralization of SARS-CoV-2 pseudovirus in convalescence and vaccine serum samples.

Panel A shows a 50% pseudovirus neutralization titer (pVNT50) Convalescent serum collected from 34 recovered patients approximately 5 months after SARS-CoV-2 infection, and received BBIBP-CorV or within 2 to 3 weeks after the second dose of anti-recombinant vesicular stomatitis virus inoculation Among the sera collected from the 50 vaccines of CoronaVac vaccine) SARS-CoV-2 pseudovirus with Wuhan-1 (wild-type) spike protein. The box plot represents the median and interquartile range (IQR); the whiskers represent 1.5 times the IQR. Figure B shows the changes in mutual serum pVNT50 Compared with the wild-type virus, the titers against D614G, B.1.1.7 and B.1.351 mutations in 34 convalescent serum samples were higher. C and D area shows the change of countdown pVNT50 Compared with the wild-type virus, the titers in serum samples obtained from 25 recipients of BBIBP-CorV vaccine and 25 recipients of CoronaVac vaccine against D614G, B.1.1.7 and B.1.351 variants were high. . The factor change of geometric mean titer and 95% confidence interval (CI) in pVNT50 The titer compared to the wild-type virus is shown under the P value. Only P values ​​less than 0.05 (indicating significance) are shown. Each data point is the average of repeated measurements. In each panel, the horizontal dashed line indicates the lower limit of detection (titer, <30); the calculated geometric mean of this limit is designated as 10 and is considered seronegative. In all panels, after adjusting the false discovery rate, the two-tailed Kruskal–Wallis test was used for calculation.

Next, we use convalescent serum obtained from 34 patients 5 months after infection with Coronavirus Disease 2019 (Covid-19) and 50 participants obtained 2 to 3 weeks after receiving the second dose of inactivated virus vaccine-BBIBP To evaluate the resistance of the pseudovirus to neutralization-CorV (Chinese National Medicine)1 piece Or CoronaVac (Sinovac)2 pcs —Developed in China (Table S1 in the Supplementary Appendix). We first determined the serum neutralizing antibody titers against wild-type pseudoviruses, and observed similar geometric mean titers (GMT) in serum obtained from convalescent patients and vaccinators (Figure 1A), which indicates that the antibody response induced by BBIBP-CorV or CoronaVac is low after two doses of vaccination.1,2 It is worth noting that undetectable neutralization titers were found in 4 of 34 convalescent serum samples, 6 of 25 BBIBP-CorV serum samples, and 4 of 25 CoronaVac serum samples.

Next, compared with the wild-type pseudovirus, we evaluated the neutralizing activity of the convalescent serum and vaccine serum against D614G, B.1.1.7 and B.1.351 variants. Convalescent serum is significantly more effective (coefficient of 2.4; confidence interval of 95% [CI](From 1.9 to 3.0) the effect in neutralizing D614G pseudovirus is similar to that of wild-type virus in neutralizing the B.1.1.7 variant, and the effect is significantly lower (coefficient of 0.5; 95% CI is 0.4) to 0.7) neutralize B.1.351 pseudovirus (Figure 1B). In addition, among 30 convalescent serum samples, 9 showed complete loss of neutralizing activity against B.1.351. For the BBIBP-CorV vaccine serum samples, although the neutralizing GMT against the variant and the wild-type virus were not significantly different, 20 serum samples showed complete or partial loss of neutralization against B.1.351 (Figure 1C). For the CoronaVac vaccine serum samples, we observed a significant reduction in GMT when the serum neutralized B.1.1.7 (coefficient of 0.5; 95% CI of 0.3 to 0.7) and B.1.351 (coefficient of 0.3). ; 95% CI, 0.2 to 0.4). In addition, most serum samples showed complete or partial loss of neutralization against B.1.351 (Figure 1D).

Our findings indicate that B.1.1.7 has little resistance to the neutralizing activity of convalescent or vaccine serum, while B.1.351 is resistant to convalescent serum (by factor 2) and vaccine serum (neutralizing a factor). Strong resistance. 2.5 to 3.3) higher than wild-type virus. Most of the vaccine serum samples tested lost neutralizing activity. This finding is in line with other recent research findings: restorative serum or serum obtained from messenger RNA or BBIBP-CorV vaccine recipients neutralizes.3-5 Our findings also emphasize the importance of continuous virus surveillance and evaluation of vaccine protection efficacy in areas where variants are endemic.

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

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

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

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

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

Lin Yao, B. Med.
Ka-Li Zhu, B. Med.
Dr. Wuchun Cao
Dr. Ma Maijuan
Beijing Institute of Microbiology and Epidemiology, Beijing
[email protected], [email protected]

Supported by a grant (L202038) provided by Beijing Natural Science Foundation And from ( National Natural Science Foundation of China, They were handed over to Dr. Ma.

The disclosure form provided by the author is available on NEJM.org for the full text of this letter.

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

Dr. G.-L. Wang and Mr. Z.-Y. Wang made the same contribution to this letter.

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