Susceptibility of Circulating Variants of SARS-CoV-2 for Neutralization

For the publisher:

The emergence of two variants of the 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 the concern that these variants may escape the immunity resulting from any infection or vaccination. In an attempt to measure the resistance of these variants to neutralization induced by infection or vaccination, we generated a SARS-CoV-2 pseudovirus based on the recombinant vesicular stomatitis virus containing the spike protein of the reference strain Wuhan-1 (wild type), the D614G mutation and variants B.1.1.7 and B.1.351. (Details on the recombination process are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.)

Figure 1. Figure 1. Neutralization of SARS-CoV-2 Pseudovirus in Convalescent and Vaccinated Serum Samples

Panel A shows the 50% pseudovirus neutralization titer (pVNT₅₀) in convalescent serum collected from 34 patients recovered approximately 5 months after infection by SARS-CoV-2 and in serum collected from 50 vaccinees who received the BBIBP-CorV or CoronaVac vaccine 2 to 3 weeks after the second dose against the stomatitis virus recombinant vesicular – SARS-CoV-2 pseudovirus based on the Wuhan-1 peak protein (wild type). The box plots indicate the median and the interquartile range (IQR); whiskers represent 1.5 times the IQR. Panel B shows changes in the reciprocal serum pVNT₅₀ titer in 34 samples of convalescent serum against variants D614G, B.1.1.7 and B.1.351, compared to the 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, against variants D614G, B.1.1.7 and B.1.351, compared to the wild-type virus. Factor changes in the title of the geometric mean and 95% confidence interval (CI) in the pVNT₅₀ the titers, compared to those of the wild-type virus, are shown under the values ​​of P. Only P values ​​less than 0.05 (indicating significance) are shown. Each data point is the average of the test results in duplicate. On each panel, the horizontal dashed line represents the lower limit of detection of the assay (title, <30); this limit was assigned a value of 10 for geometric mean calculations and was considered seronegative. In all panels, calculations were performed using the two-tailed Kruskal-Wallis test after adjusting for the false discovery rate.

Then, we evaluated the resistance of the pseudovirus to neutralization using convalescent serum obtained from 34 patients 5 months after infection with coronavirus 2019 (Covid-19) and serum from 50 participants obtained 2 to 3 weeks after receiving the second dose of vaccines. inactivated virus – BBIBP -CorV (Sinopharm)¹ or 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 (GMTs) in the serum obtained from convalescent and vaccinated patients (Figure 1A), which suggested a low antibody response after the two-dose inoculation induced by BBIBP-CorV or CoronaVac.^1.2 Notably, undetectable neutralization titers were observed in 4 of 34 convalescent serum samples, in 6 of 25 BBIBP-CorV serum samples and in 4 of 25 CoronaVac serum samples.

Next, we evaluated the neutralizing activity of the convalescent serum and the vaccinated serum against the variants D614G, B.1.1.7 and B.1.351 in comparison with the 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 the neutralization of the D614G pseudovirus, had a similar effect to that of the wild type virus in the neutralization of variant B.1.1.7 and was significantly less effective (by a factor of 0.5; IC 95 %, 0.4 to 0.7) in the neutralization of pseudovirus B.1.351 (Figure 1B) In addition, 9 out of 30 convalescent serum samples showed complete loss of neutralizing activity against B.1.351. For samples of vaccinated serum BBIBP-CorV, although the GMTs of neutralization against the variants were not significantly different from the GMTs against the wild-type virus, 20 serum samples showed complete or partial loss of neutralization against B.1.351 (Figure 1C) For the CoronaVac vaccinated serum samples, we observed a marked decrease in GMTs in the neutralization of serum from B.1.1.7 (by a factor of 0.5; 95% CI, 0.3 to 0.7) and B. 1,351 (by a factor 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 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). 2.5 to 3.3) than the 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 studies of neutralization by convalescent serum or serum obtained from messenger RNA containers or BBIBP-CorV vaccines.^3-5 Our results also highlight the importance of sustained viral monitoring and assessment of the vaccine’s protective efficacy 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 Services 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, at NEJM.org.