Mu SARS-CoV-2 variant highly resistant to neutralization by convalescent and vaccinated sera

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Researchers in Japan have warned that variant Mu (B.1.621) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease 2019 (COVID-19), appears to be highly resistant to the neutralization by serums of convalescent or vaccinated individuals.

Variant B.1.621, first isolated in Colombia in January this year (2021), was classified as a variant of interest by the World Health Organization (WHO) on 30 August.th.

Now, Kei Sato and colleagues have conducted a study that showed that the variant was more resistant to serum-mediated neutralization than all other variants of interest or concern identified so far.

This includes the South African beta lineage (B.1.351) which had hitherto been recognized as the most resilient.

“Since new emerging variant infection is a major concern during the current COVID-19 pandemic, we believe our findings have a significant interest in public health,” writes the University of Tokyo, Kyoto University team. , Chiba and Tokai University. Kanagawa University.

“Our results will help to better assess the risk posed by the Mu variant for previously infected and naive vaccine populations.”

A preprinted version of the research work is available at bioRxiv* server, while the article is undergoing peer review.

Study: Ineffective neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine serum. Image credit: NIAID

More information on the variants that have emerged so far

Since the COVID-19 outbreak first began in late December 2019, the evolution of the SARS-CoV-2 causative agent has led to the emergence of four worrying variants, including the alpha (B. lineage). 1.1.7) which first emerged in the United Kingdom and the beta (B.1.351), gamma (P.1) and delta (B.1.617.2) lineages identified in South Africa, Brazil and India, respectively.

Five variants of interest have also appeared, including the eta (B.1.525), iota (B.1.526), ​​kappa (B.1.617.1), lambda (C.37) and Mu (B.1.621) lineages. . Nigeria, New York, India, Peru and Columbia, respectively.

The most recently recognized of these variants is the B.1.621 lineage, which the WHO classified as a new variant of interest on 30 August.th. At this point, the lineage had been detected in 39 countries.

In Colombia, where the variant was first isolated in January, there was a huge rise in COVID-19 between March and August, with cases reaching a maximum of 33,594 daily on June 26.th.

Although the worrying variant P.1 (gamma) was dominant during the initial phase of this increase, B.1.621 outperformed P.1 and all other variants in May and has since driven the epidemic to Colombia.

Emerging variants need to be carefully evaluated

The WHO defines “comparative assessment of virus characteristics and public health risks” as the main action to be taken in response to the emergence of new variants of SARS-CoV-2.

Variants need to be carefully controlled to increase transmission, pathogenicity, and resistance to immune responses. Resistance to humoral immunity caused by infection or natural vaccination with SARS-CoV-2 may allow significant viral transmission in populations that would otherwise have been considered protected.

The resistance exhibited by emerging variants to date can be attributed to several mutations that have arisen in the spike viral protein, the main structure involved in mediating infection of host cells.

Most B.1.621 variants have the following eight mutations: T95I, YY144-145TSN, R346K, E484K, N501Y, D614G, 57 P681H, and D950N.

Several of these mutations are commonly seen in worrying variants, including E484K (present in B.1.351 and P.1), N501Y and P681H (present in B.1.1.7) and D950N (present in B.1.617.2).

What did the researchers do?

To assess the sensitivity of B.1.621 to convalescent or vaccinated serum neutralization, Sato and colleagues generated and compared different pseudoviruses containing B.1.621 tip proteins or other variants of concern and interest.

Characterization of the Mu variant. (A) Outbreak of SARS-CoV-2 in Colombia. The new cases of COVID-19 per day (black line, axis and left) and the percentage of different variants of SARS-CoV-2 that extend to Colombia (axis and right) are shown. The daily frequency of Gamma (P.1), Delta (B.1.617.2, AY.4, AY.5, AY.12), Lambda (C.37), Mu (B.1.621) and other variants are shows in the indicated colors. Note that there are some Delta VOCs (the most dominant variant currently in the world) and Lambda VOIs (a variant that extends mainly to South American countries) so far isolated in that country. The figure indicates the date on which the Mu variant was first isolated (January 11, 2021). Virus neutralization tests. A pseudovirus-containing neutralization assay containing the SARS-CoV-2 tip proteins of the Alpha, Beta, Gamma, Delta, Epsilon, Lambda, Mu, or parental virus housing D614G was performed. Eight COVID-19 (B) convalescent sera and ten sera from people vaccinated with BNT162b2 (C) were tested. The assay of each serum was performed in triplicate to determine the 50% neutralization titer and each data point represents the 50% neutralization titer obtained with a serum sample against the indicated pseudovirus. Bar charts indicate geometric mean titles with 95% confidence. Bar numbers indicate geometric mean titles. The numbers of the bars in parentheses (with

Characterization of the Mu variant. (A) Outbreak of SARS-CoV-2 in Colombia. The new cases of COVID-19 per day (black line, axis and left) and the percentage of different variants of SARS-CoV-2 that extend to Colombia (axis and right) are shown. The daily frequency of Gamma (P.1), Delta (B.1.617.2, AY.4, AY.5, AY.12), Lambda (C.37), Mu (B.1.621) and other variants are shows in the indicated colors. Note that there are some Delta VOCs (the currently most dominant variant in the world) and Lambda VOIs (a variant that extends mainly to South American countries) that have been isolated in this country so far. The figure indicates the date on which the Mu variant was first isolated (January 11, 2021). Virus neutralization tests. A pseudovirus-containing neutralization assay containing the SARS-CoV-2 tip proteins of the Alpha, Beta, Gamma, Delta, Epsilon, Lambda, Mu, or parental virus housing D614G was performed. Eight convalescent serums COVID-19 (B) and ten sera from people vaccinated with BNT162b2 (C) were tested. The assay of each serum was performed in triplicate to determine the 50% neutralization titer and each data point represents the 50% neutralization titer obtained with a serum sample against the indicated pseudovirus. Bar charts indicate geometric mean titles with 95% confidence. Bar numbers indicate geometric mean titles. The numbers of the bars in parentheses (with “X”) indicate the average of bending changes in the neutralization resistance of the indicated ear variants compared to that of the parental ear of each serum. Statistical analysis was performed using the Wilcoxon signed rank test. Horizontal dashed lines indicate the limit of detection.

Virus neutralization assays revealed that B.1.621 was 12.4 times more resistant to sera taken from eight convalescent COVID-19s that became infected between April and September 2020 than the parental virus.

The variant was also 7.6 times more resistant to sera obtained from ten individuals who had been immunized with the Pfizer-BioNTech BNT162b2 vaccine compared to the parental virus.

A direct comparison of all pseudoviruses revealed that B.1.621 was more resistant to serum-mediated neutralization than all other currently recognized variants of interest and concern.

What do the authors advise?

“The Mu variant shows pronounced resistance to antibodies caused by natural SARS-CoV-2 infection and the BNT162b2 mRNA vaccine,” writes Sato et al.

“Since advanced infections pose a significant threat to emerging new SARS-CoV-2 variants, we strongly suggest characterizing and controlling the Mu variant,” they conclude.

* Important news

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

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