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 UK and B.1.351 in South Africa, has raised concerns that these variants may escape immunity resulting from infection or vaccination. In an attempt to measure the resistance of these variants to neutralization caused by infection or vaccination, we generated recombinant SARS-CoV-2 pseudoviruses based on vesicular stomatitis virus containing the peak protein of the Wuhan reference strain. 1 (wild type), the D614G Mutation, and the B.1.1.7 and B.1.351 variants. (Details on the recombination process are provided in the Supplemental Appendix, available with the full text of this letter at NEJM.org).

Neutralization of SARS-CoV-2 pseudovirus in convalescent serum samples and vaccines.

Panel A shows the 50% pseudovirus neutralization titer (pVNTfifty) in convalescent serum collected from 34 patients recovered approximately 5 months after SARS-CoV-2 infection and in serum collected from 50 vaccinates who had received the BBIBP-CorV or CoronaVac vaccine 2 to 3 weeks after the second dose against Recombinant vesicular stomatitis virus -Pseudovirus SARS-CoV-2 based on Wuhan-1 spike protein (wild type). Box plots indicate the median and interquartile range (IQR); whiskers represent 1.5 times the IQR. Panel B shows changes in the reciprocal serum pVNTfifty titer in 34 convalescent serum samples against the D614G, B.1.1.7 and B.1.351 variants, compared to the wild-type virus. Panels C and D show changes in reciprocal pVNTfifty titer in serum samples obtained from the 25 recipients of the BBIBP-CorV vaccine and from the 25 recipients of the CoronaVac vaccine, respectively, against the variants D614G, B.1.1.7 and B.1.351, compared to the virus of wild type. Changes in the geometric mean factor of the titer and the 95% confidence interval (CI) in the pVNTfifty the titers, in comparison with those of the wild-type virus, are shown under the P values. Only P values ​​less than 0.05 are shown (indicating significance). Each data point is the average of duplicate test results. In each panel, the horizontal dashed line represents the lower limit of detection of the assay (titer, <30); This limit was assigned a value of 10 for the calculations of the geometric mean and it was considered seronegative. In all panels, calculations were performed using the two-tailed Kruskal-Wallis test after adjustment for the false discovery rate.

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

Next, we evaluate the neutralizing activity of the convalescent serum and the vaccinated serum against the D614G, B.1.1.7 and B.1.351 variants compared to wild-type pseudovirus. Convalescent serum was significantly more effective (by a factor of 2.4, 95% confidence interval [CI], 1.9 to 3.0) in neutralizing pseudovirus D614G, had a similar effect to that of wild-type virus in neutralizing variant B.1.1.7, and was significantly less effective (by a factor of 0, 5, 95% CI 0.4 to 0.7) in the neutralization of pseudovirus B.1.351 (Figure 1B). Furthermore, 9 out of 30 convalescent serum samples showed a complete loss of neutralizing activity against B.1.351. For the serum samples of the BBIBP-CorV vaccines, although the neutralization GMTs against the variants were not significantly different from the GMTs against the wild-type virus, 20 serum samples showed total or partial loss of neutralization against B.1.351 (Figure 1C). For the serum samples from the CoronaVac vaccines, we observed a marked decrease in GMTs in serum neutralization of B.1.1.7 (by a factor of 0.5; 95% CI, 0.3 to 0.7) and B.1.351 (by a factor 0.3, 95% CI 0.2 to 0.4). Furthermore, most of the serum samples showed total or partial loss of neutralization against B.1.351 (Figure 1D).

Our findings suggest that B.1.1.7 showed little resistance to the neutralizing activity of the convalescent or vaccinated serum, while B.1.351 showed more resistance to the neutralization of both the convalescent serum (by a factor of 2) and the vaccinated serum (by a factor of 2.5 to 3.3) than wild-type virus. Most of the vaccinated serum samples that were tested lost neutralizing activity, a finding that was consistent with the results of other recent neutralization studies by convalescent serum or serum derived from messenger RNA receptors or BBIBP-CorV vaccines.3-5 Our findings also highlight the importance of sustained viral monitoring and evaluation of the protective efficacy of vaccines in areas where variants circulate.

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 Service 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]

With the support of a grant (L202038) from the Beijing Natural Science Foundation and a grant (81773494) from China Natural Science Foundation, both to Dr. Ma.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

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

Dr. G.-L. Wang and Mr. Z.-Y. Wang also contributed to this letter.

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  2. two. Zhang Y, Zeng g, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 to 59 years: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial. Lancet Infect Dis 2021; twenty-one:181192.

  3. 3. Huang B, Dai L, Wang H, et al. Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by inactivated BBIBP-CorV vaccines and recombinant dimeric RBD ZF2001 vaccines. February two, 2021 (https://www.biorxiv.org/content/10.1101/2021.02.01.429069v1). prepress.

  4. Four. Liu Y, Liu J, Xia H, et al. BNT162b2-induced serum neutralizing activity – preliminary report. N Engl J Med. DOI: 10.1056 / NEJMc2102017.

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  5. 5. Wang P, Nair MS, Liu L, et al. Resistance to antibodies to SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 2021 March 8 (Epub ahead of print).

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