COVID 19 mutations and implications for the vaccines

[pinball1970]

TL;DR Summary

SARS-CoV-2 501Y.V2 escapes neutralization by south African Donar plasma. 18.1.21

SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma.

SARS-CoV-2 501Y.V2 escapes neutralization by south African Donar plasma

from the abstract

SARS-CoV-2 501Y.V2, a novel lineage of the Coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.

https://www.biorxiv.org/content/10.1101/2021.01.18.427166v1.full.pdfThe paper states that.

"spike mutations in the 501Y.V2 lineage confer neutralization escape from multiple classes of SARS-CoV-2 directed monoclonal antibodies. Furthermore, we observe significantly increased neutralization resistance of 501Y.V2 to plasma from individuals previously infected with SARS-CoV-2, with implications for both rates of re-infection, and vaccine effectiveness."

Also.

" Ultimately, the correlates of protection against SARS-CoV-2 infection and severe COVID-19 disease remain undetermined and rely upon ongoing large-scale clinical trials. "

UK government statements are talking about the new strains more and more now and the take away is that the vaccine will still be effective although the language seems to have changed from when the vaccine was first rolled out.

It would be good to have a professional view of the paper from @atyy @jim mcnamara @Dale @berkeman @BillTre @Ygggdrasil off the top of my head

 

[Ygggdrasil]

There are multiple lines of evidence suggesting that specific mutations in the spike protein (in particular E484K) in the B.1.351 variant (aka 501Y.V2) from South Africa and the P.1 variant from Brazil allow the virus to escape immunity from antibodies that recognize the original SARS-CoV-2 spike protein.

1) Laboratory experiments looking at how mutations to the spike (S) protein show that antibodies from convalescent sera are much less effective at recognizing S proteins with mutations at E484: https://www.biorxiv.org/content/10.1101/2020.12.31.425021v1

2) Sera from people immunized with the Moderna mRNA vaccine is less effective at neutralizing the B.1.351 variant than the original virus: https://www.biorxiv.org/content/10.1101/2021.01.25.427948v1
(note, however, that Pfizer reports that its vaccine is effective at neutralizing viruses containing the E484K mutation: https://www.biorxiv.org/content/10.1101/2021.01.27.427998v1)

3) Phase 3 clinical trials of new COVID-19 vaccines from Novavax and Johnson & Johnson showed lesser efficacy at preventing infection in South Africa and Brazil (where the newer variants are more common) versus in the UK (where the E484 mutant viruses are not as prevalent).

4) Scientists previously reported that ~76% of the population in Manaus, Brazil had been infected during the first wave of COVID-19 in Spring 2020. However, the same location has seen a major resurgence of the virus in recent months, with hospitalization rates exceeding those seen during the Spring 2020 peak. The P.1 variant of the virus was first detected in Manaus, Brazil and is the main strain spreading in that area.

Other research is also identify other nearby sites where mutations can allow the virus to evade immunity, for example the N439K mutation: https://www.sciencedirect.com/science/article/pii/S0092867421000805?via=ihub

For more discussion of the SARS-CoV-2 mutations see: https://www.physicsforums.com/threads/sars-cov-2-mutations.998345/

 

[atyy]

4) Scientists previously reported that ~76% of the population in Manaus, Brazil had been infected during the first wave of COVID-19 in Spring 2020. However, the same location has seen a major resurgence of the virus in recent months, with hospitalization rates exceeding those seen during the Spring 2020 peak. The P.1 variant of the virus was first detected in Manaus, Brazil and is the main strain spreading in that area.

Was the antibody test specific? Could there have been an overestimate by cross reaction to dengue?
https://www.sciencedirect.com/science/article/pii/S1201971220322487

Dengue prevalence in Rio from 2018 data is estimated at 28%.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243239

 

[Ygggdrasil]

Was the antibody test specific? Could there have been an overestimate by cross reaction to dengue?
https://www.sciencedirect.com/science/article/pii/S1201971220322487

Dengue prevalence in Rio from 2018 data is estimated at 28%.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243239

That's a fair point. There are a number of (non-mutually exclusive) different potential explanations that could contribute to the resurgence of COVID in Manaus: 1) The prevalence of COVID-19 could have been overestimated, 2) immunity to the virus may wane over a short period of time, 3) The P.1 strain evades immunity (likely via the E494K mutation), and 4) The P.1 strain has a higher transmissibility (likely due to the N501Y mutation). The Lancet article I cited in my previous post discusses these possibilities further:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00183-5/fulltext

 

[atyy]

https://www.economist.com/the-ameri...ity-thought-it-had-herd-immunity-it-was-wrong
"It could be that the study’s methodology is flawed and that 76% was an overestimate. Blood donors are more likely to leave the house, and therefore to get infected, than most people, says Pedro Hallal, an epidemiologist at the Federal University of Pelotas. A nationwide study he co-ordinated, with population samples picked at random, found that just 15% of Manaus residents had antibodies in June. He thinks the preprint’s authors were “not cautious enough” in interpreting their findings."

https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30387-9/fulltext
SARS-CoV-2 antibody prevalence in Brazil: results from two successive nationwide serological household surveys
Pedro C Hallal, Fernando P Hartwig, Bernardo L Horta, Mariângela F Silveira, Claudio J Struchiner, Luís P Vidaletti, Nelson A Neumann, Lucia C Pellanda, Odir A Dellagostin, Marcelo N Burattini, Gabriel D Victora, Ana M B Menezes, Fernando C Barros, Aluísio J D Barros, Cesar G Victora

... It would be good to have a professional view of the paper from @atyy ...

Just to be clear, I'm not a professional.