The Lambda variant: is it more infectious, and can it escape vaccines? A virologist explains

[Celerity]

https://theconversation.com/the-lambda-variant-is-it-more-infectious-and-can-it-escape-vaccines-a-virologist-explains-164156

The Lambda coronavirus variant was first reported in Peru in December 2020, according to the World Health Organization (WHO). It then spread to multiple countries in South America, where it currently accounts for over 20% of detected variants. One case of Lambda was recorded in hotel quarantine in New South Wales in April. Lambda has now been detected in more than 20 countries around the globe. The European Centre for Disease Prevention and Control has designated Lambda a “variant under monitoring”, and Public Health England regards it as a “variant under investigation”. In June this year, the WHO designated it a “variant of interest”. This is due to mutations thought to affect the virus’ characteristics, such as how easily it’s transmitted. Though it’s not yet concerning enough for the WHO to deem it a “variant of concern”, such as Alpha or Delta. Epidemiological evidence is still mounting as to the exact threat Lamda poses. So, at this stage more research is required to say for certain how its mutations impact transmission, its ability to evade protection from vaccines, and the severity of disease. Preliminary evidence suggests Lambda has an easier time infecting our cells and is a bit better at dodging our immune systems. But vaccines should still do a good job against it.

Link to tweet

Is Lambda more infectious? And can it escape vaccines?

Mutations affecting the spike protein of the SARS-CoV-2 virus can increase infectivity, which is the ability of the virus to infect cells. What’s more, as many of the coronavirus vaccines currently available or in development are based on the spike protein, changes to the spike protein in new variants can impact vaccine effectiveness. Lambda contains multiple mutations to the spike protein. One mutation (F490S) has already been associated with reduced susceptibility to antibodies generated in patients who had recovered from COVID. This means antibodies generated from being infected with the original Wuhan strain of COVID aren’t quite as effective at neutralising Lambda. Another Lambda mutation (L452Q) is at the same position in the spike protein as a previously studied mutation found in the Delta variant (L452R). This mutation in Delta not only increases the ability of the virus to infect cells, but also promotes immune escape meaning the antibodies vaccines generate are less likely to recognise it. Both mutations F490S and L452Q are in the “receptor binding domain”, which is the part of the spike protein that attaches to our cells. Preliminary data on the Lambda spike protein suggests it has increased infectivity, meaning it’s more easily able to infect cells than the original Wuhan virus and the Alpha and Gamma variants.

Link to tweet

These early studies also suggest antibodies generated in people receiving the CoronaVac vaccine (developed by Chinese biotech Sinovac) were less potent at neutralising the spike protein of Lambda than they were the Wuhan, Alpha or Gamma variants. It’s worth noting infectivity is not the same as being more infectious between people. There’s not enough evidence yet that Lambda is definitely more infectious, but the mutations it has suggest it’s possible. A separate small study, also yet to be reviewed by the scientific community, suggests the L452Q mutation in the Lambda spike protein is responsible for its increased ability to infect cells. Like the L452R mutation in the Delta variant, this study suggests the L452Q mutation means Lambda may bind more easily to the “ACE2 receptor”, which is the gateway for SARS-CoV-2 to enter our cells. This preliminary study suggests Lambda’s spike protein mutations reduce the ability of antibodies generated by both Pfizer and Moderna’s vaccines to neutralise the virus. Also, one mutation was shown to resist neutralisation by antibodies from antibody therapy to some extent. However, these reductions were moderate. Also, neutralising antibodies are only one part of a protective immune response elicited by vaccination. Therefore, these studies conclude currently approved vaccines and antibody therapies can still protect against disease caused by Lambda.

Is it more severe?

A risk assessment released by Public Health England in July concedes there’s not yet enough information on Lambda to know whether infection increases the risk of severe disease. The risk assessment also recommends ongoing surveillance in countries where both Lambda and Delta are present be implemented as a priority. The aim would be to find out whether Lambda is capable of out-competing Delta. With ongoing high levels of transmission of the coronavirus, there’s a continued risk of new variants emerging. The Lambda variant again highlights the risk of these mutations increasing the ability of SARS-CoV-2 to infect cells or disrupt existing vaccines and antibody drugs. The WHO will continue to study Lambda to determine whether it has the potential to become an emerging risk to global public health and a variant of concern.

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[SheltieLover]

1. K&R!

[Celerity]

3. To answer your question from earlier today

They did not have the data yet, mainly do to the duration required to label someone as a true long hauler. Delta has simply not been in zones where these Western studies are done long enough to determine an accurate percentage. They were sceptical of the Indian data.

As for Lambda versus the variant tweaked mRNA-1273.351 vaccine that we are in the trial study for, they only have lab mock-ups (as opposed to wild virus studies), but they preliminarily think to should come in well over 90% efficacy, so that is a positive. It is crushing the South African (B.1.351 aka Beta) and the Brasilian (P.1 aka Gamma) variants. Over 96% efficacy so far.

As for the mRNA-1273.351 variant tweaked vaccine versus Delta, they are extremely optimistic, as even the original Moderna vax had much higher antibody titer counts versus Delta than most of the other variants. Beta (the SA variant) kicked the original Moderna's arse, which is which they based the tweaked version off it.

The relative reductions in neutralizing titers for the original mRNA-1273 Moderna vax (the one 99.999999% of people have had) were as follows:

Gamma: 3.2-fold reduction
Kappa: 3.3–3.4-fold
Eta: 4.2-fold
Beta: 7.3–8.4-fold
Delta: 2.1-fold

if you want a deep dive on that, here you go

Serum Neutralizing Activity of mRNA-1273 against SARS-CoV-2 Variants

https://www.biorxiv.org/content/10.1101/2021.06.28.449914v1.full

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to growing concerns over increased transmissibility and the ability of some variants to partially escape immunity. Sera from participants immunized on a prime-boost schedule with the mRNA-1273 COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants, including variants of concern (VOCs) and variants of interest (VOIs), compared to neutralization of the wild-type SARS-CoV-2 virus (designated as D614G). Results showed minimal effects on neutralization titers against the B.1.1.7 (Alpha) variant (1.2-fold reduction compared with D614G); other VOCs such as B.1.351 (Beta, including B.1.351-v1, B.1.351-v2, and B.1.351-v3), B.1.617.2 (Delta), and P.1 (Gamma) showed decreased neutralization titers ranging from 2.1-fold to 8.4-fold reductions compared with D614G, although all remained susceptible to mRNA-1273–elicited serum neutralization.

INTRODUCTION

As the coronavirus disease 2019 (COVID-19) pandemic continues to escalate in various parts of the world, several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of interest (VOIs) and variants of concern (VOCs) have emerged, including in the United States (B.1.526; Iota), United Kingdom (B.1.1.7; Alpha), Brazil (P.1; Gamma), India (B.1.617.1, Kappa; B.1617.2, Delta), South Africa (B.1.351; Beta), Uganda (A.23.1), Nigeria (B.1.525; Eta), and Angola (A.VOI.V2).1 There is growing concern over these variants based on increased transmissibility and the ability of some variants to partially escape both natural and vaccine-induced immunity. Notably, the B.1.617.2 lineage was recently classified as a VOC by the World Health Organization due to evidence of an increased rate of transmission, reduced effectiveness of monoclonal antibody treatment, and reduced susceptibility to neutralizing antibodies.1

We previously reported that mRNA-1273, a lipid nanoparticle encapsulated mRNA-based vaccine encoding the spike glycoprotein of the SARS-CoV-2 Wuhan-Hu-1 isolate, induced high neutralizing antibody titers in phase 1 trial participants2 and was highly effective in preventing symptomatic and severe COVID-19.3,4 Some VOCs or VOIs, including B.1.351 and P.1, reduced neutralizing antibody levels using a pseudovirus-based model.5 Importantly, however, all variants remained susceptible to mRNA-1273 vaccine–elicited serum neutralization.5 Here we provide an update on the neutralization activity of vaccine sera against several newly-emerged variants, including the Delta variant B.1.617.2.

[LisaL]

4. I hope we are actually allowed to have boosters.

NT

[Celerity]

6. the people who got the J&J will likely need one, I would say ASAP (and it should be an mRNA vax)

You are one of the few who is not fixating on death count alone, in terms of breakthrough infections. There is a multiplicity of other adverse effects that come come from a non lethal COVID case, and some of those are likely permanent.

There are 'variant versus specific vax' pairings that can simply be labelled as pretty much fails in terms of even preventing infection. The classic one so far is AstraZeneca versus Beta (10.4% efficacy), but here are other pairings that are also far from ideal in terms of staving off infections and/or mitigation of the severity of the symptoms.

[LisaL]

7. Unfortunately we have to wait for guidance from FDA and CDC, which have

recently declared we are in no need of boosters right now. I dunno when they are going to decide we need boosters.
I hope by that time everybody is not dropping dead.

[Celerity]

8. they were talking mostly about a booster for the 2 mRNA double shot ones, not the single dose J&J

[StarryNite]

17. Have there been studies to show if it's safe to mix and match?

[Celerity]

18. multiple countries, including Canada, are already doing it

Several countries have allowed mixing COVID vaccines: Here is all you need to know

https://timesofindia.indiatimes.com/life-style/health-fitness/health-news/several-countries-have-allowed-mixing-covid-vaccines-here-is-all-you-need-to-know/photostory/84579458.cms

[StarryNite]

19. Thank you Celerity.

It kind of flips back and forth as to whether they know for sure if it's safe to do. On one hand it makes it seem like everyone should be mixing and matching when it comes to boosters. But on the other hand they don't really seem to know if it's safe...

"The immunogenicity and tolerability results from several clinical trials have shown that there is no harm in mixing and matching COVID-19 vaccines right now, and instead, it would only build better immune strength. However, there's no relevant, or substantial data to support the safety as yet."

[Celerity]

21. hopefully they can sort it, I am all in on mRNA vaccines, they are the future, without them atm, the

world would be fucked

they are incredibly modular and thus adaptable on the relative fly

such a wonderful scientific breakthrough we are witnessing

shame it is counterbalanced (hopefully only to point) by the incredibly destructive force of another new tech paradigm (social media)



In a speech in Cape Town, South Africa, in June 1966, Robert Kennedy said (likely the curse is semi-made up, but the point still stands):

There is a Chinese curse which says 'May he live in interesting times.' Like it or not we live in interesting times. They are times of danger and uncertainty; but they are also more open to the creative energy of men than any other time in history.

[womanofthehills]

20. The WHO said studies should be done before combining

[SheltieLover]

9. Wow! Tyvm!

And ty for participating in a study!

I saw (& posted thread about) a manufacturer us going to help manufacture mRNA vaxes for Africa!!!

[Arger68]

2. Why do I get the feeling that

Anti-vaxxers are going to kill us all in the end??

[Carlitos Brigante]

5. They sure as shit seem to be trying. nt

[Initech]

11. Oh they're trying all right.

[Initech]

10. Oh come on!!!!!

We haven't even finished with the Delta variant and now there's one that's possibly worse?

[LisaL]

12. Covid never stops improving.

NT

[colsohlibgal]

13. Damn The Anti Vaccine Fools

This is all on them. You are almost totally responsible for where we are and where we might be heading.

[Celerity]

14. +10000000000000000

[inwiththenew]

15. It was only a matter of time

Whether this one will be it or not I don't know. But eventually we are going to get a mutation that will set us back to square one. Every person infected with the virus is a potential vector for it to mutate. You give it enough chances and eventually it's going to come out with something to escape the vaccines.

[Celerity]

16. yes, and there is a name for it (VOHC) Variant of High Consequence

https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html