Neutralization of SARS-CoV-2 variants B.1.429 and B.1.351

To the editor:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.429 (also known as CAL.20C or 542R.V1), first identified in California,¹ spreads rapidly in the United States and has been found in at least 25 other countries (see updates at https://www.gisaid.org/hcov19-variants/). This variant contains three peak mutations which are the main targets for the neutralization of antibodies. one mutation (L452R) is located in the receptor-binding motif, and another (W152C) in the N-terminal domain supersite. This raised concerns about possible immune flight, which could impair the effectiveness of the vaccine and increase the risk of re-infection. We measured the neutralizing activity of serum samples obtained from 14 recovering individuals and from 49 recipients of one of the two different vaccines, based on the ancestral peak: an mRNA vaccine (mRNA-1273 [Moderna]; 26 recipients)² and a protein nanoparticle vaccine (NVX-CoV2373 [Novavax]; 23 recipients).³ We selected mRNA-1273 samples representing high, medium, and low neutralization titers. NVX-CoV2373 samples were randomly selected and were not preselected based on antibody titers.

The neutralizing activity of all serum samples was tested against the B.1.429 variant and a worrying variant that first emerged in South Africa (B.1.351, also called 20H / 501Y.V2). We compared this neutralizing activity with the activity displayed by the serum samples against the prototypical D614G variant. Compared to the D614G variant, we found that B.1.429 was approximately 2 to 3 times less sensitive to neutralization due to repair problem and by vaccines obtained from vaccines, while B.1.351 was approximately 9 to 14 times less sensitive to neutralization. .

Figure 1. Figure 1. Neutralization of B.1.429 and B.1.351 Pseudoviruses in serum samples obtained from repairers and vaccine recipients.

Restorative serum samples were obtained from infected persons 1 to 8 weeks after the resolution of the coronavirus disease 2019 infection or 2 to 10 weeks after the most recent positive SARS-CoV-2 test. Serum samples were obtained on day 57 from the recipients of the Moderna vaccine (28 days after the second vaccine dose), and Novavax serum samples were obtained on day 35 from the vaccine recipients (14 days after the second vaccine dose). Results are shown as the difference in neutralization titers of corresponding samples (panels A and B) and the difference in titers relative to the D614G variant (the ratio of titers to the indicated variant) for each sample set (panel C). Lower values ​​indicate stronger cross-neutralization of the variant virus. Thin stripes in panels A and B represent individual samples, and thick black lines represent the geometric means of each sample group, as shown on the right. Thick black bars in panel C represent the geometric mean titer differences for the sample sets, which are also marked above each set. Circles in panel C represent the differences in titers relative to D614G for individual samples. P-values ​​for the comparison of the reciprocal neutralization titers at 50% inhibitory dilution (ID₅₀) and 80% inhibitory dilution (ID₈₀) are some comparisons of the data shown in panels A and B, calculated using the Wilcoxon-drawn rank test. P values ​​less than 0.001 correlate with Q (adjusted P) values ​​less than 0.0019 (see Table S2 in Supplementary Appendix 2). Differences in the neutralization titers between the three sample sets shown in panel C were not significant (P> 0.05 by the Wilcoxon rank-sum test).

We compiled pseudoviruses with the D614G peak mutation alone (as the comparative variant) or combined with the additional mutations listed in B.1.429 (S13I, W152C and L452R) and B.1.351 (L18F, D80A, D215G, Δ242-224, R246I , found), K417N, E484K, N501Y and A701V). Neutralization assays were performed using a validated lentivirus-based spike pseudotypic virus assay in 293T cells stably transferred to the expression of angiotensin-converting enzyme 2.⁴ The variant B.1.429 was neutralized by restorative serum and by serum obtained from vaccines, which resulted in 50% inhibitory dilution (ID₅₀geometric mean titers from 225 to 495 (Figure 1A, and Table S1 in Supplementary Appendix 1, available with the full text of this letter at NEJM.org). The ID₅₀ an ID₈₀ the titers against the B.1.429 variant for restorative serum and serum of persons who received one of the vaccinations were significantly lower than those against D614G (P <0.001) (Figures 1A and 1Band Table S2 in Supplementary Appendix 2). The geometric mean ID₅₀ titers at B.1.429 were 3.1 times (range, 1.4 to 8.8) lower than those against D614G for restorative serum and were 2.0 and 2.5 times (range, 0.7 and 8.6) lower than versus D614G for serum from persons receiving the mRNA 1273 and NVX-CoV2373 vaccines, respectively (Figure 1C and Table S1). The geometric mean ID₅₀ titer at B.1.351 was 13.1-fold lower than versus D614G for restorative serum and 9.7-fold and 14.5-fold lower than versus D614G for serum from subjects receiving the mRNA-1273 and NVX-CoV2373 vaccines, respectively. (Figure 1C). Our findings regarding neutralization of the B.1.351 variant by serum obtained from recipients of the mRNA-1273 vaccine are similar to those previously reported.⁵

The modest lower value in neutralization titers compared to the B.1.429 variant seen in this study is similar to that we saw previously when neutralization of the B.1.1.7 variant was tested with the same test using serum samples that was obtained from recipients of the mRNA-1273 and NVX-CoV2373 vaccines.⁴ These results, and the high efficacy of these vaccines, suggest that neutralizing antibodies elicited by the vaccine are likely to remain effective against the B.1.429 variant. The extent of the resistance seen with the B.1.351 variant is of greater concern with respect to current vaccines.

Xiaoying Shen, Ph.D.
Haili Tang, MS
Duke University, Durham, NC
[email protected]

Rolando Pajon, Ph.D.
Moderna, Cambridge, MA

Gale Smith, Ph.D.
Gregory M. Glenn, Managing Director
Novavax, Gaithersburg, MD

Wei Shi, Ph.D.
National Institute of Allergy and Infectious Diseases, Bethesda, MD

Bette Korber, Ph.D.
Los Alamos National Laboratory, Los Alamos, NM

David C. Montefiori, Ph.D.
Duke University, Durham, NC
[email protected]

This letter was published on April 7, 2021 on NEJM.org.