More terrible than the British strain: South African coronavirus variant can significantly evade antibody attack

Currently, there are three different variants of the novel coronavirus, from the UK, South Africa and Brazil. Whether the existing COVID-19 vaccines are effective against the new variants will determine the direction of the global epidemic prevention and control situation. In vitro experiments have shown that the existing vaccines are effective against the UK variant, but it remains to be seen whether they are effective in the human body. But this week, a preprint paper on the South African variant brought worrying news and quickly attracted the attention of scientists.

Written by Idobon and Shi Jun

Original title: "More terrible than the British strain: South Africa's new coronavirus variant can significantly evade antibody attacks, and the new coronavirus vaccine may need to be updated丨117 Three People"

On the last day of 2020, the World Health Organization (WHO) released a Disease Outbreak News [1] that mentioned four new coronavirus variants that have attracted widespread attention and discussion: the D614G variant, the British variant of the coronavirus B.1.1.7, the South African variant of the coronavirus 501Y.V2, and the Danish mink variant.

Among them, the D614G variant had already swept the world as early as late February 2020, becoming the mainstream strain of the new coronavirus prevalent in Europe and the United States. In June 2020, the new coronavirus was transmitted back to humans through minks, but there were relatively few cases of infection, and it has not been found in humans since September [2].

The latest novel coronavirus variant was discovered in a sample collected in the Amazon state of Brazil. On January 14, 2021, researchers discovered multiple mutations, including in the spike protein[3], and named it the P.1 variant. Subsequently, Japan, South Korea and other countries confirmed the first case of infection with the P.1 variant[4]. Currently, research on the P.1 variant is still ongoing.

Currently, the most reported in the media is the British coronavirus variant B.1.1.7. On September 21, 2020, the UK first discovered a variant of the coronavirus. From November to December, this variant spread rapidly in the UK and became the most common strain in the UK. On December 19, British Prime Minister Boris Johnson said that the new variant virus B.1.1.7 may be 70% more transmissible than previously discovered viruses[5], and implemented new fourth-level strict epidemic prevention measures in London and other areas. More than 40 countries and regions around the world have imposed travel bans on the UK. However, all this still cannot stop the spread of the virus. On January 20, 2021, two cases caused by the British B.1.1.7 variant were discovered in Daxing, Beijing, making the domestic prevention and control situation in China even more severe[6].

Can the existing COVID-19 vaccine resist the variant from the UK? On January 7 and January 19, Pfizer researchers published the latest research data on the biological preprint website bioRxiv [7, 8], showing that the company's mRNA vaccine can still neutralize the B.1.1.7 variant from the UK.

However, it is actually the South African variant that is most worrying.

In early December 2020, the South African government announced to the world the new variant of the coronavirus, 501.V2 (also known as 501Y.V2). This mutation, like the British variant, is also on the spike protein, and it has three main mutations: K417N, E484k and N501Y[9]. Initial studies have shown that the 501.V2 variant has a higher viral load, spreads faster and is more transmissible. According to the European Centre for Disease Prevention and Control Rapid Risk Assessment (ECDC Rapid Risk Assessment) report on December 29, 2020, the 501Y.V2 strain first appeared in early August 2020, and by early November, it had become the main virus strain in South Africa, and later appeared in the UK and other countries. As of the end of December last year, the proportion of 501Y.V2 strains in the number of infections in South Africa exceeded 80%[10].

For the 3D structural diagram of the novel coronavirus variant 501Y.V2 [2], please go to the “Fanpu” public account to view it.

On January 19, Wibmer et al., researchers at the National Institute for Communicable Diseases (NICD) of South Africa, published a preprint paper titled SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma on bioRxiv[11]. The paper states that the new coronavirus variant 501Y.V2 that emerged in South Africa can significantly escape the attack of three types of related monoclonal antibodies. Worse still, the neutralizing antibodies in the serum of recovered patients also have a significantly reduced effect on the variant. The research data suggests that the South African variant of the new coronavirus is likely to "re-infect" people, and the current vaccines based on the spike protein may be powerless against it and have reduced efficacy.

As soon as the paper was published, it immediately attracted attention. Trevor Bedford, a well-known virus research expert at the Fred Hutchinson Cancer Research Center in the United States, posted ten consecutive tweets on Twitter to discuss the research results[12].

Bedford re-plotted the data in the preprint to make the data look clearer. In the figure below, each line represents the serum from a recovered patient. The blue dot on the left is the neutralizing antibody titer against the wild-type new coronavirus in the serum (y-axis data), and the blue dot on the right is the neutralizing antibody titer against the 501Y.V2 variant virus in the serum. Note that the titer value is logarithmic data.

Obviously, in all the recovered serum samples used in the study, the neutralizing titer against the 501Y.V2 variant was reduced. To give an intuitive example, a 2-fold reduction in the titer of neutralizing antibodies means that twice as much recovered serum is needed to neutralize the same amount of virus.

The figure below is a distribution diagram of the reduction in neutralizing titers of 44 sample sera against the 501Y.V2 variant. As can be seen from the figure, compared with the neutralizing antibody titers against the wild-type virus strain, the antibody titers produced by the convalescent sera against the 501Y.V2 variant were reduced by an average of 8 times. Specifically for each sample, some samples did not decrease, but some even decreased by as much as 64 times.

What is the significance of these specific values ​​of reduction multiples?

Take the flu vaccine for example. If the flu virus mutates and the neutralizing antibody titer of the existing flu vaccine against the variant is reduced by 8 times, the WHO will recommend making a new flu vaccine. Of course, the new coronavirus is different from the flu virus, and the neutralization results may not be directly comparable, but it can be inferred that the limit of whether the new coronavirus vaccine needs to be updated will also be around this value. In other words, the new coronavirus vaccine may also need to be updated seasonally.

This may mean that the vaccine antigen needs to make some changes to adapt to the mutations in the spike protein on the variant. Judging from the existing data, mRNA vaccines are a very good choice, and the antigens can be modified. On the one hand, it can induce a strong immune response; on the other hand, the initial neutralization effect is high (the efficacy of mRNA vaccines is as high as 95%), and the impact after reduction is always better than that of vaccines with low initial neutralization effects (the effect after reduction is even lower). In addition, a single mutation in an antigen usually has little effect on the polyclonal immune response induced. Because mRNA vaccines can induce a strong immune response, the efficacy of the vaccine should not be significantly reduced unless the vaccine is significantly modified.

This preprint paper only investigated the titer of neutralizing antibodies. We do not yet know the direct correlation between the titer of neutralizing antibodies and the protective effect of vaccines. In other words, does a weakening of the effect of neutralizing antibodies necessarily mean a weakening of the protective effect in the human body? We have not yet concluded.

For now, the 501Y.V2 variant remains largely confined to South Africa, but it (or other variants) may spread more widely in the coming months.

If further research confirms the findings of this preprint, then based on seasonal influenza data, it is likely that by the fall of 2021 we will need to modify existing vaccine designs to adapt to new variants.

References

[1] https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/

[2] https://sarscov2.sinica.edu.tw/doc/20210109.html

[3] https://time.com/5931366/brazil-new-covid-19-strain/

[4] https://www.yicai.com/news/100918138.html

[5] https://www.bbc.com/news/health-55388846

[6] http://www.xinhuanet.com/2021-01/20/c_1127005868.htm

[7] https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1

[8] https://www.biorxiv.org/content/10.1101/2021.01.18.426984v1

[9] https://doi.org/10.1101/2020.12.21.20248640

[10] https://www.ecdc.europa.eu/en/publications-data/covid-19-risk-assessment-spread-new-sars-cov-2-variants-eueea

[11] https://www.biorxiv.org/content/10.1101/2021.01.18.427166v1

[12] https://twitter.com/trvrb/status/1351785356782313473