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Neutralization of the SARS-CoV-2 variables B.1.429 and B.1.351.



To the editor:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.429 (also known as CAL.20C or 542R.V1), first seen in California.1 It is spreading rapidly in the US and in at least 25 other countries (see updates at https://www.gisaid.org/hcov19-variants/) This variant consists of three hindered mutations, the main goal of neutralizing the antibodies. One mutation (L452R) is located in the receptor binding motif and the other (W152C) in the northern portion of the N terminal domain. It is possible, which could affect the effectiveness of the vaccine and increase the risk of re-infection. We measured the neutralization activity of the serum samples obtained from 1

4 patients and from 49 vaccine recipients from one of two different vaccines, based on ancestral increases: the mRNA vaccine (mRNA-1273). [Moderna]; 26 recipients)2 And protein nanoparticle vaccine (NVX-CoV2373 [Novavax]; 23 recipients).3 We selected mRNA-1273 samples showing high, medium and low neutralization titers, NVX-CoV2373.The samples were randomly selected and were not pre-selected based on the antibody titer.

The neutralization activities of all serum samples were tested against variable B.1.429 and the first concern variant in South Africa (B.1.351, also known as 20H / 501Y.V2). In comparison with D614G, we found that B.1.429 was approximately 2 to 3 times less susceptible to neutralization by the recovery serum and by the resulting serum sample. Received from vaccinated subjects, while B.1.351 was approximately 9 to 14 times less susceptible to neutralization.

Neutralization of B.1.429 and B.1.351 Pseudoviruses. In the serum sample received from the patient and vaccine recipient.

A recovery serum sample was obtained from an infected person 1 to 8 weeks after the coronavirus disease 2019 infection, or 2 to 10 weeks after the most recent positive SARS-CoV-2 test. The serum sample was obtained by Moderna vaccine recipients on Day 57 (28 days after receiving the second vaccination) and Novavax serum samples were obtained from vaccine recipients on Day 35 (14 days after second vaccination). The results are shown as titer difference, matching sample neutralization (panels A and B), and titer difference relative to variable D614G (titer ratio to the specified variable. ) For each sample set (panel C), lower values ​​represent stronger cross-strain neutralization of different viruses.The thin dashed lines in panels A and B represent each sample, and the thick black lines show. To the geometric mean of each sample, as indicated to the right. The thick black bar in panel C represents the titer differences, the geometric mean for the sample set, labeled above each set.The circle in panel C represents the titer difference relative to D614G. For each sample, the P value for comparison of mutual neutralization titers at 50% inhibition dilution (ID50) And 80% inhibition dilution (ID80) Is a comparison of the data shown in panels A and B paired, calculated using Wilcoxon’s signed rank test.P-values ​​less than 0.001 are relative to Q (improved P) values ​​less than 0.0019 (see Table S2 in Appendix 2). The difference in the neutralization titer between the three sample sets shown in panel C was not significant (P> 0.05 by the Wilcoxon rated sum test).

We create pseudoviruses. With just the D614G needle mutation (As a comparative variable) or combined with additional mutations found in B.1.429 (S13I, W152C, and L452R) and B.1.351 (L18F, D80A, D215G, Δ242–244, R246I, K417N, E484K, N501Y, and A701V). Neutralization tests are performed using virus testing. Investigated lentivirus spike-pseudotyped in 293T cells stably transmitted to too much angiotensin-converting enzyme.4 Variant B.1.429 was neutralized by the recovery serum and by serum obtained from vaccinated subjects, resulting in a 50% dilution of inhibition (ID50Heading Geometric Mean 225 to 495 (Figure 1AAnd Schedule S1 in Addendum 1, along with the full body of this letter at NEJM.org) code50 And ID80 titers compared with variable B.1.429 for the recovery serum and for the serum from one of the vaccine subjects were significantly lower than D614G (P <0.001) (Figures 1A and 1BAnd Table S2 in Supplementary Appendix 2) ID Geometric Mean.50 The titers compared with B.1.429 were 3.1 times lower (range, 1.4 to 8.8), lower than D614G for recovery serum, and 2.0 and 2.5 times lower (range, 0.7 and 8.6) than D614G for serum from mRNA-treated subjects. – Vaccines 1273 and NVX-CoV2373, respectively (Figure 1C And Table S1) ID geometric mean50 The titer compared with B.1.351 was 13.1 times lower than D614G for recovery serum and 9.7 times lower than D614G, 14.5 times lower for serum from mRNA-1273 and NVX-CoV2373 vaccine subjects, respectively (Figure 1COur findings on the neutralization of the B.1.351 variant by serum obtained from mRNA-1273 vaccine recipients are consistent with previously reported.5

The slightly lower values ​​in the neutralization titer compared to the B.1.429 variable seen in this study were similar to what we saw earlier when testing the neutralization of the B.1.1.7 variable with the same assay using a sample. Serum obtained from mRNA-vaccine 1273 and NVX-CoV2373 recipients.4 These results, and the high efficacy demonstrated by these vaccines, suggest that the immunized neutralizing antibodies tend to be effective against the B.1.429 variable, the magnitude of the resistance seen with the B. variable. 1.351 There were more concerns compared to current vaccines.

Xiaoying Shen, PhD
Haili Tang, MS
Duke University, Durham, NC
[email protected]

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

Gale Smith, PhD
Gregory M. Glenn, MD
Nova Wax, Gaithersburg, MD

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

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

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

Dr. Shen and Montefiori are supported by the grant. (3UM1-AI068618-14S1) from file COVID-19 protection networkKorber received a grant (XB3W00) from Los Alamos National Laboratory.

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

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

  1. 1. Zhang W., Davis BD, Chen SS, Martinez JMS, Plummer JT, Vail EThe emergence of a new strain SARS-CoV-2 in southern California, USA. January 20, 2564 (https://www.medrxiv.org/content/10.1101/2021.01.18.21249786v1) pre-print

  2. 2. Anderson EJ, Rufael NG, Widge AT, Et al. Safety and immunogenicity of the SARS-CoV-2 mRNA-1273 vaccine in the elderly. N Engl J Med. 2020; 383:24272438.

  3. 3. Quiche, Albert G., For me, Et al. Phase 1-2 trials of a non-combinant spike protein-blocking vaccine against SARS-CoV-2 activity. N Engl J Med. 2020; 383:23202332.

  4. 4. Shen X, Tang H., McDonald’s, Et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies obtained from ancestral vaccine. Cell host microbiome 2564 March 05 (Epub ahead of print).

  5. 5. Woo k, Werner AP, Cook, Et al. Serum neutralization activity was induced by mRNA-1273 vaccine. N Engl J Med. DOI: 10.1056 / NEJMc2102179.

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