Lambda variant shows vaccine resistance

[Evo]

TL;DR Summary

Lambda variant shows vaccine resistance

The Lambda variant of the coronavirus, first identified in Peru and now spreading in South America, is highly infectious and more resistant to vaccines than the original version of the virus the emerged from Wuhan, China, Japanese researchers have found.

Well, if the Delta variant wasn't enough, now this seems to be rearing it's head.

Lambda variant shows vaccine resistance

The Lambda variant of the coronavirus, first identified in Peru and now spreading in South America, is highly infectious and more resistant to vaccines than the original version of the virus the emerged from Wuhan, China, Japanese researchers have found. In laboratory experiments, they found that three mutations in Lambda's spike protein, known as RSYLTPGD246-253N, 260 L452Q and F490S, help it resist neutralization by vaccine-induced antibodies. Two additional mutations, T76I and L452Q, help make Lambda highly infectious, they found. In a paper posted on Wednesday on bioRxiv https://bit.ly/3fpi5Fn ahead of peer review, the researchers warn that with Lambda being labeled a "Variant of Interest" by the World Health Organization, rather than a "Variant of Concern," people might not realize it is a serious ongoing threat. Although it is not clear yet whether this variant is more dangerous than the Delta now threatening populations in many countries, senior researcher Kei Sato of the University of Tokyo believes "Lambda can be a potential threat to the human society."

Also

Third mRNA dose may boost antibody quantity, but not quality

Among fully vaccinated people who never had COVID-19, getting a third dose of an mRNA vaccine from Pfizer/BioNTech or Moderna would likely increase levels of antibodies, but not antibodies that are better able to neutralize new virus variants, Rockefeller University researchers reported on Thursday on bioRxiv https://bit.ly/3fnbk6Y ahead of peer review. They note that in COVID-19 survivors, the immune system's antibodies evolve during the first year, becoming more potent and better able to resist new variants. In 32 volunteers who never had COVID-19, they found that antibodies induced by mRNA vaccines did evolve between the first and second shots. But five months later, vaccine-induced antibodies were "equivalent" to those seen after the second dose, with "little measurable improvement" in the antibodies' ability to neutralize a broad variety of new variants, said coauthor Michel Nussenzweig. Therefore, he said, giving those individuals a third dose of the same vaccine would likely result in higher levels of antibodies that remain less effective against variants. "At the moment, the vaccine remains protective against serious infection," Nussenzweig said.

continued

https://news.yahoo.com/delta-infections-among-vaccinated-likely-192553854.html

 

[fresh_42]

Third mRNA dose may boost antibody quantity, but not quality

But wasn't quantity the problem? They said last year that the severity of illness was proportional to the virus load. So it seems that fighting quantity isn't that bad. But I do not know whether this was true for the original version, which I think it was, and whether this is still true for the variants.

 

[Evo]

But wasn't quantity the problem? They said last year that the severity of illness was proportional to the virus load. So it seems that fighting quantity isn't that bad. But I do not know whether this was true for the original version, which I think it was, and whether this is still true for the variants.

I don't know, it just says "Therefore, he said, giving those individuals a third dose of the same vaccine would likely result in higher levels of antibodies that remain less effective against variants."

So it sounds like it doesn't do any better in the long run. But time will tell, and the virus will continue to mutate.

 

[Rive]

But wasn't quantity the problem?

Sometimes quantity is a problem: for example, Sinopharm (the Chinese vaccine) is known to produce low antibody levels for elderly.
Some vector-based vaccines may not work for some people due immunity against the vector.
Antibody levels falling with time.

Generally, if by any reason the antibody levels are low, a third shot (against the original version of the virus) would likely help.
If the levels are high, then it would be better to give it to somebody else.

I thought that modified vaccines will be (widely) available by autumn. Looks like I was wrong

 

[atyy]

It seems the decrease in antibody neutralization ability is only about 3x, which is small. It's in the same range for Delta, and bigger decreases have been reported for the Beta (B.1.351) variant. For Delta, while it means the vaccine has reduced effectiveness for infection and perhaps severe disease, as far as we know the reductions for severe disease have been much less (about 97% to 90% in Israel, and maybe no or just a few percent in UK data). Protection from severe disease depends a lot on T cell responses, and these are negligibly affected by various variants. So I wouldn't worry (any extra) about Lambda (famous last words ).

 

[Jarvis323]

It seems the decrease in antibody neutralization ability is only about 3x, which is small. It's in the same range for Delta, and bigger decreases have been reported for the Beta (B.1.351) variant. For Delta, while it means the vaccine has reduced effectiveness for infection and perhaps severe disease, as far as we know the reductions for severe disease have been much less (about 97% to 90% in Israel, and maybe no or just a few percent in UK data). Protection from severe disease depends a lot on T cell responses, and these are negligibly affected by various variants. So I wouldn't worry (any extra) about Lambda (famous last words ).

The scare about the Lambda variant began based on its exceptionally high case fatality rate in Peru, which was about 9.3%, where it was dominant.

https://www.forbes.com/sites/brucel...ronavirus-is-spreading-what-you-need-to-know/

Peru also has by far the most deaths per capita (almost by a factor of 2).

But it was considered to likely be due to the poor conditions in Peru rather than the Peruvian variant being more deadly. I wonder if they have figured that out yet.

The scary thing is that we don't really know what future variants could do. We think T cell immunity is pretty good, even T cell immunity from decades old SARS-1 and MERS infections have shown to provide some lasting cross reactive T cell protection against SARS-CoV-2. So that is assuring, but I don't know how much. For all we know, several mutations from now, a future variant could end up with a lethality closer to MERS (~30%) while maintaining the infectiousness of SARS-CoV-2. If that happens, we better hope that most people around the world have acquired significant cross reactive T-Cell protective immunity before hand.

 

[morrobay]

The poor conditions in the Peru population include obesity and overweight, 52%. https://clas.berkeley.edu/research/...is conducted by,children are at greatest risk.

 

[bhobba]

So I wouldn't worry (any extra) about Lambda (famous last words ).

In support of that, Lamda is not outcompeting Delta in the US, where it certainly has become part of the Covid variants. Around the world, the Delta variant looks like it will become the dominant variant due to its very high R0. Alarmingly here in Brisbane, it is hitting the young hard:
https://theconversation.com/school-...eak-change-the-story-of-how-it-spreads-165601

New vaccination tactics are being implemented targeting the young - and reassuringly, they are responding.

Regarding a third booster dose, please keep in mind many researchers are working on second-generation vaccines that have efficacy against all variants, e.g.:
https://www.gavi.org/vaccineswork/could-universal-coronavirus-vaccine-soon-be-reality

Fingers crossed, they will be ready for the third dose. Other vaccines are coming online, like Novavax, which may be better suited as a booster, but more research is required.

Thanks
Bill

 

[Evo]

I moved a few posts concerning delta mutations in an elderly immuno-compromised patient in the Lamda discussion thread, so i moved those and @atyy 's great responses to the Delta thread.

 

[StevieTNZ]

Evidence suggested an eight-week gap created better immunity, he said. The Ministry of Health currently says people should get two doses at least three weeks apart.

-- https://www.stuff.co.nz/national/he...rket-for-annual-covid19-vaccine-booster-shots

 

[bhobba]

-- https://www.stuff.co.nz/national/he...rket-for-annual-covid19-vaccine-booster-shots

At the beginning of the Pandemic, many thought, including me, it would end up like the Flu with a jab each year. I have even read researchers are working on a combination flu/covid jab. The main thing with Covid is not the death rate when vaccinated. It likely is better than the Flu. R0 is the problem. 1.4-1.6 for the Flu - 8 for Delta. The vaccines need to get that down by reducing the viral load and/or how well it protected people.

Thanks
Bill

 

[Astronuc]

https://www.newsweek.com/lambda-variant-covid-louisiana-cases-texas-vaccine-1616875

The first cases of the Lambda variant of COVID, which is showing resistance to vaccines in Tokyo, Japan, have been detected in Louisiana, while the country still continues to respond to rising cases and hospitalizations caused by the Delta Variant.

WBRZ reported on Thursday that the Lambda variant, which is believed to have originated in Peru and was first reported in the U.S. in Houston, Texas, has now been recorded in northern Louisiana, which shares a border with the Lone Star State.

. . .
Two mutations in the Lambda variant—T76I and L452Q—make it more infectious than the COVID variant that swept through the world in 2020, according to the study.

. . . .

Could have come on a flight from Lima to Houston (IAH).

So watch the numbers in Harris County and Houston, and Louisiana from Lake Charles to New Orleans.

The Newsweek article refers to "data by Statista shows that around 6,000 people have contracted COVID after getting vaccinated, the number is still very small compared to the 165 million people who are fully vaccinated in the country." Ok, that's a small percentage - yes.

I don't understand this graph - https://www.newsweek.com/lambda-var...cases-texas-vaccine-1616875#slideshow/1864171
Breakthrough cases as of July 26, 2021 - 6587 breakthrough cases, but how does this value related to
1291 asymptomatic infections, 6239 hospitalizations, 1263 deaths?

Then in the same graphic, it is stated, "As of April 30, the CDC count of all breakthrough cases was 10262 cases, 995 hospitalizations, and 160 deaths.

Newsweek - "The U.S. recorded 127,108 news COVID cases on Thursday, which was up from the 112,270 seen in the country on Wednesday. The U.S. has now recorded a seven-day average of at least 100,000 new cases over the last week." Most of these are the Delta variant.

The day before the aforementioned article, Newsweek reported - Lambda COVID Variant 'a Potential Threat to Human Society,' Researchers Say.
https://www.newsweek.com/lambda-covid-variant-potential-threat-society-researchers-1616556

So let's see.

https://www.biorxiv.org/content/10.1101/2021.07.28.454085v1.full

Summary - SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America.

 

[bhobba]

Could have come on a flight from Lima to Houston (IAH).

I think the chances of keeping any variant out is next to zero. It is the R0 of the variant. The Delta with an R0 of 8 outcompetes any other varient I know of. No wonder it is quickly becoming the dominant varient in the world. And it is a beast. As I mentioned before, here in Brisbane, when it got in a school cluster, it is young people - primary and secondary school age - that are the majority of cases.

Although I have not read of anything happening for a vaccine to tackle this varient, I hope researchers are hot on its trail.

Thanks
Bill

 

[atyy]

The Newsweek article refers to "data by Statista shows that around 6,000 people have contracted COVID after getting vaccinated, the number is still very small compared to the 165 million people who are fully vaccinated in the country." Ok, that's a small percentage - yes.

Estimates of protection from infection range against the Delta variant range from 40-80%. So it should be possible for a large percentage of vaccinated people to be infected. However, protection against severe disease remains high at about 90%. It does mean that vulnerable populations should perhaps receive a booster at an appropriate time, as we would like protection against severe disease to be 95% or better to make COVID more similar to flu in terms of severe disease.
80% https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01358-1/fulltext
64% https://www.forbes.com/sites/robert...a-variant-heres-what-we-know/?sh=7a0b9232ff33
40% https://www.haaretz.com/israel-news...ata-preventing-hospitalizations-88-1.10021477
49% https://fortune.com/2021/08/04/covid-vaccine-delta-variant-efficacy-uk-study/

 

[bhobba]

It does mean that vulnerable populations should perhaps receive a booster at an appropriate time, as we would like protection against severe disease to be 95% or better to make COVID more similar to flu in terms of severe disease.

Well said. All I would add is everyone should get a booster. When boosters against specific dominant varients come out, everyone should get one as well.

Thanks
Bill

 

[Ygggdrasil]

Estimates of protection from infection range against the Delta variant range from 40-80%. So it should be possible for a large percentage of vaccinated people to be infected. However, protection against severe disease remains high at about 90%. It does mean that vulnerable populations should perhaps receive a booster at an appropriate time, as we would like protection against severe disease to be 95% or better to make COVID more similar to flu in terms of severe disease.
80% https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01358-1/fulltext
64% https://www.forbes.com/sites/robert...a-variant-heres-what-we-know/?sh=7a0b9232ff33
40% https://www.haaretz.com/israel-news...ata-preventing-hospitalizations-88-1.10021477
49% https://fortune.com/2021/08/04/covid-vaccine-delta-variant-efficacy-uk-study/

This probably gives a skewed view of vaccine efficacy. Only one (the highest figure, 80%) is a study published in a peer-reviewed journal. The next two (64% and 40%) reflect preliminary data from the same study in Israel (from press releases two weeks apart), where the methods and data have still yet to be released, so it is difficult to assess their reliability (see this article for a discussion of the difficulties of doing such research and correctly accounting for confounding variables).

The 49% figure does come from a non-peer reviewed study from the UK, based on swabs sent to random samples of the population in England: https://spiral.imperial.ac.uk/bitstream/10044/1/90800/2/react1_r13_final_preprint_final.pdf

Your post omits other studies supporting higher efficacy of the mRNA vaccines against the Delta variant, including:

88% (peer-reviewed, published study by Public Health England): https://www.nejm.org/doi/full/10.1056/NEJMoa2108891
87% (non-peer-reviewed pre-print from Ontario, Canada): https://www.medrxiv.org/content/10.1101/2021.06.28.21259420v2

So, for studies where we have methods and data available, we have estimates of 80%, 49%, 88% and 87%. Note that the REACT-1 study from the UK (which gave the 49% estimate), used somewhat different methods than the others (based on community survey rather than a case-control design like the others), which could be one reason why it seems like an outlier (potentially not correcting for confounding variable like the other studies).

Further reading:
https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html
https://www.factcheck.org/2021/07/v...ariant-counter-to-claims-from-fox-news-guest/

 

[Astronuc]

July 19, 2021 - SARS-CoV-2 Lambda Variant: The New Kid on the Block
https://gvn.org/sars-cov-2-lambda-variant-the-new-kid-on-the-block/

The Lambda variant has a characteristic suite of mutations, some (but not all) of which are shared by other variants. One mutation is a 3 codon deletion in the ORF1A gene (∆S3675- F3677), which is also found in the gamma variant (P.1 or the Brazilian variant). This similarity caused the lambda variant to originally be misclassified as the gamma variant. Of note, this deletion may enable the virus to suppress host immune function and interferon-based activity(1). Other key mutations in the lambda variant are 6 amino acid substitutions and a 7 amino acid deletion in the spike (S) protein.

 

[atyy]

Your post omits other studies supporting higher efficacy of the mRNA vaccines against the Delta variant, including:

88% (peer-reviewed, published study by Public Health England): https://www.nejm.org/doi/full/10.1056/NEJMoa2108891
87% (non-peer-reviewed pre-print from Ontario, Canada): https://www.medrxiv.org/content/10.1101/2021.06.28.21259420v2

I did not cite the 88% PHE and 87% Canadian numbers as they refer to symptomatic infection, and omit asymptomatic cases. I agree that the lower numbers may give a skewed view, but I don't agree with ignoring them because methods are not published. The methods for the 64% figure from Israel have been available (I can no longer find them, but I have seen them on the Israeli government's website, and they are cited in the CDC slides (p19) that also cite the PHE 88% and Canadian 87%), and the 40% being from the same source presumably uses the same methods. The reason they may give a skewed view has to do with sample size, as well as difficulties in doing the base rate correction. In the Israeli data, it may be that the cases come mainly from highly vaccinated cities, and thus using the vaccination rates from larger geographical areas in the base rate correction are not correct.

There are other preprints that show falling effectiveness against infection with time, which may be due to falling antibody levels or variants. Protection against severe disease remains high.
https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v1 (infection: 96.2% to 90.1% to 83.7%; severe disease: 97%)
https://www.medrxiv.org/content/10.1101/2021.08.03.21261496v1 (odds ratios given, I don't see VE estimates, data probably overlaps with those for the earlier mentioned Israeli estimates)

 

[rayj]

This is a great discussion. It is often productive to address such question as a decision process. We have a lot of statistics of subsets of populations for responses to different pathogens along with confounding factors. Such questions may help lead us to making more valuable decisions on what actions to take. To appropriately assess the decision alternatives, we should be able to distinguish between expected results for each such decision. Even with the inconsistency in record keeping, analyses may be able to differentiate efficacy across the alternatives. These could be improved if we had more detailed information on the specific variations between the COVID variants and the specific codings used in each of the vaccines.

In consider of NIH studies of corona viruses 16 years ago, they reported that across the strains of corona viruses, the common conserved proteins were the trimers in the viral spike. To address efficacy for variants, it is critical to know upon which proteins our existing vaccines are based. As new variants emerge, we would be better equipped to make knowledgeable decisions for our responses.

We also have the emerging understanding of bacterial process which inhibit virus infections – CRISPR:
https://www.livescience.com/[URL='h...chnologies-wont-lead-designer-babies/']crispr-block-coronavirus-replication-treatment.html[/URL]

 

[Ygggdrasil]

Summary:: Lambda variant shows vaccine resistance

From the non-peer-reviewed pre-print study cited in the quote, the researchers found that the spike protein from the Lambda variant is 1.5x more resistant to neutralizing antibodies than the D614G variant.

Here's a nice paper that uses a similar assay to look at how much the spike protein of other variants resist neutralizing antibodies from vaccinated individuals:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01290-3/fulltext?s=09

We know from various observational studies and clinical trials, that the vaccine very effectively protects against the D614G and the Alpha (B.1.1.7) variants but some vaccines show lesser efficacy against the Beta (B.1.351) and Delta (B.1.617.2) variants. Although it is difficult to directly compare the values between the two papers, the data would seem to suggest that the resistance of the Lambda variant (~3.5x more resistant than wild-type; 1.5x more resistant than D614G) would fall between the Alpha variant and the Beta variant in terms of ability to evade antibody-based immunity.

Given that the vaccine still shows fairly good protection (~80-90%) against symptomatic disease from the Delta variant (though protection from asymptomatic infection may be as low as 50%), this would suggest that the vaccine should still be similarly effective or better against the Lambda variant (at least considering only the effects of neutralizing antibodies). As @atyy noted above, the T-cell response is probably not affected much by these variants, and should still provide good protection against severe disease, hospitalization and death.

 

[neilparker62]

By way of interest what's the 'status' of naturally acquired immunity in all of this ? For example I recently had Covid (or at least according to the test result I had it - third test now + 31/05, - 01/06 + 30/06) but luckily only suffered relatively mild flu-like symptons. I would guess it's the Delta variant but don't know for sure. Have I "self-vaccinated" ? How effective is naturally acquired immunity ? Will it deal with new variants and finally how long should I wait before going for vaccination? (Had every intention of being vaccinated but they hadn't got round to my age group at that point in time).

 

[Ygggdrasil]

By way of interest what's the 'status' of naturally acquired immunity in all of this ? For example I recently had Covid (or at least according to the test result I had it - third test now + 31/05, - 01/06 + 30/06) but luckily only suffered relatively mild flu-like symptons. I would guess it's the Delta variant but don't know for sure. Have I "self-vaccinated" ? How effective is naturally acquired immunity ? Will it deal with new variants and finally how long should I wait before going for vaccination? (Had every intention of being vaccinated but they hadn't got round to my age group at that point in time).

A study in the UK estimated the risk of re-infection after an initial COVID-19 infection, and found that prior infection confers ~ 84% protection against any re-infection, and a 93% protection against symptomatic infections (Hall et al. 2021). A study in Denmark similarly found an 80% protection against re-infection, though this protection was less effective in those aged >65 (47%) (Hansen et al. 2021). These levels of protection are somewhat lower than the ~90% protection observed for the mRNA vaccines (Pfizer-BioNTech and Moderna), though they are comparable or higher than the protection observed with the adenoviral vectored vaccines (Johnson & Johnson and Oxford-AstraZeneca) (see data compiled at https://alsnhll.github.io/covid19_vaccine_comparison.html). Notably, the clinical trial data for the Pfizer mRNA vaccine showed no drop in efficiency in older individuals (95% effective in age >65 vs 95% overall) (Polack et al. 2020) and the Moderna vaccine showed only a small drop in efficacy (86% effective in age >65 vs 94% overall) (Baden et al. 2021).

While it looks like prior infection does protect similarly as vaccination, the CDC still recommends that people who recovered from COVID-19 still get vaccinated (CDC FAQ). We do know that immunity to other coronaviruses is fairly short lived after initial infection (~ 1 year) (Edrige et al. 2020). One might hypothesize that vaccinating those previously exposed to the Coronavirus would help stimulate the production of memory B and T cells that would make the immune response much more durable and longer lasting. Indeed, various studies are beginning to show that vaccination boosts immunity in those previously infected with COVID-19 (https://apnews.com/article/science-health-coronavirus-pandemic-ad52011f4ca1853fad6eee41a7310c2e).

Nevertheless, the vaccines have been administered to millions of people and shown to be very safe, so it does not hurt to get vaccinated if you are previously infected. The main issues may be the inconvenience of having to take time off of work to get vaccinated and/or deal with side effects.

 

[neilparker62]

Thanks very much for the very comprehensive answer - I will definitely go ahead with vaccination! Inconveniences mentioned are very minor compared to benefits.