Lyme disease - USA clinical trials of Lyme disease vaccines, 2023

[Sly Saint]

Yahoo news: A woman is trying out a 4-dose Lyme disease vaccine as we approach the worst summer for ticks yet

• Two pharmaceutical companies, Pfizer and Valneva, are developing a vaccine to prevent Lyme disease in people ages 5 and up.
  
  
• They expect the clinical trial to be over by the end of 2025.

Mindi Weidow vividly remembers the moment she found her first tick.

She was getting undressed after a hike in woodsy Pennsylvania and found a tiny, pinhead-sized critter nestled near the bottom of her legging in the warm, snug spot where her pant leg met her ankle.

The tick had not burrowed too far into her skin yet, and she was able to pull it off without too much hassle.

Her father, however, was not so lucky.

Several years ago, a tick burrowed its way under his skin, and unleashed a nasty form of the borrelia bacteria into his blood. It wasn't until around two months later that lab tests confirmed he had Lyme disease. Weidow's father was then treated with antibiotics, but he still weathers arthritic flare ups and inflammation to this day, symptoms of what the CDC has deemed Post-Treatment Lyme Disease.

Now, Weidow is hoping that an experimental series of injections she's received might help her avoid the same fate. She is a participant in Pfizer's Vaccine Against Lyme for Outdoor Recreationists trial, or VALOR, the only late-stage lyme disease vaccine trial. If successful, the VALOR trial could herald a brand new way to prevent lyme disease, the widely underdiagnosed condition that may impact up to 500,000 Americans every year, and can lead to chronic, debilitating pain — and in rare cases, even death.

Researchers estimate that roughly 15% of the world has had Lyme disease at some point. Symptoms can range from near imperceptible and flu-like at first, to life-threatening heart problems. The condition isn't always simple for blood tests to pinpoint, because people often test negative early on. Contrary to popular belief, there is not always a visible bull's-eye rash on the skin from a tick bite.

https://uk.news.yahoo.com/woman-try...yW4np-1duTlm1snyr6XL8aXu9CupxauXVpimZhpqDSlHU

 

[Trish]

CDC article:

Clinical trials
Clinical trials of new vaccines for Lyme disease are currently underway. Valneva and Pfizer have developed a Lyme disease vaccine candidate, VLA15, that is currently in Phase 3 human trials. VLA15 is a multivalent, protein subunit vaccine that targets the outer surface protein A (OspA) of Borrelia. This vaccine is designed to protect people against North American and European strains of the Lyme disease bacterium.

The University of Massachusetts Medical School’s MassBiologics has developed a human monoclonal antibody designed to be used as pre-exposure prophylaxis (PrEP) for Lyme disease. Human trials are expected to begin soon. This approach would provide seasonal protection against Lyme disease. It would likely consist of a single shot that people would get each year at the beginning of tick season.

What is CDC doing?
CDC is currently conducting research to understand what concerns healthcare providers and the public may have about any potential Lyme disease vaccines. Once a Lyme disease vaccine is approved as safe and effective by the Food and Drug Administration (FDA), CDC will work with the Advisory Committee on Immunization Practices (ACIP) to develop recommendations about where in the U.S. the public might benefit from a Lyme disease vaccine. CDC will communicate these recommendations to increase awareness of a vaccine among the public and clinicians to prevent Lyme disease in the United States.

 

[FMMM1]

Interesting - if they vaccinate and people still get "Lyme" then ---?

The EU spent about 5 million euros funding research to develop a PCR diagnostic test --- which yielded nothing --- suggesting there isn't a persistent pathogen [i.e. causing post treatment Lyme] and/or there's another pathogen [other than Borrelia burgdorferi]?

I'd like to see a GWAS study in Lyme/further larger GWAS studies in Lyme.

From - "Preprint The genetics of ME: a commentary on Hajdarevic et al. Chris P. Ponting1 and Simon J. McGrath2"
"Inevitably, the lack of a diagnostic test for ME introduces misdiagnosed individuals into ME cohorts. There is interesting evidence of this in the UK Biobank. A common genetic variant strongly associated with diagnosed Lyme disease (Strausz et al., 2022*) is also modestly associated with CFS in the UK Biobank cohort (p=2.4x10-3 ; Dönertaş et al., 2021). This could be explained by some UK Biobank participants with Lyme disease being diagnosed with CFS instead. Future studies will need to be inclusive – resulting in larger cohort sizes and greater statistical power – and also exclusive – removing from consideration any individual lacking core symptoms of ME, especially postexertional malaise."
*Strausz, S., Blacker, G., Galloway, S., Hansen, P., Jones, S.E., Sanders, E., Sinnott-Armstrong, N., FinnGen, Weissman, I.L., Daly, M., Aivelo, T., Caspi Tal, M., Ollila, H.M. 2022. Secretoglobin family 1D member 2 (SCGB1D2) protein inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease. bioRxiv. https://doi.org/10.1101/2022.05.27.493784
https://mecfsresearchreview.me/wp-c...nting-McGrath-2022-BBI-The-genetics-of-ME.pdf

 

[duncan]

What is CDC doing?

Yes, what is the CDC doing? And the NIH?

Clinical trials of new vaccines for Lyme disease are currently underway. Valneva and Pfizer have developed a Lyme disease vaccine candidate, VLA15, that is currently in Phase 3 human trials. VLA15 is a multivalent, protein subunit vaccine that targets the outer surface protein A (OspA) of Borrelia. This vaccine is designed to protect people against North American and European strains of the Lyme disease bacterium.

Another OspA vaccine. It may not be a bad idea for someone considering taking a new vaccine to find out what happened with the first almost 25 years ago. Do the research as opposed to letting questionable sources do it for one.

 

[duncan]

The EU spent about 5 million euros funding research to develop a PCR diagnostic test --- which yielded nothing --- suggesting there isn't a persistent pathogen [i.e. causing post treatment Lyme] and/or there's another pathogen [other than Borrelia burgdorferi]?

The simpler take-away is a PCR is lacking as a diagnostic when a given pathogen flees blood.

A common genetic variant strongly associated with diagnosed Lyme disease (Strausz et al., 2022*)

Yeah, this would be a dangerous association regardless of the infection being researched. Genes don't cause Lyme disease; a spirochete does.

 

[FMMM1]

The simpler take-away is a PCR is lacking as a diagnostic when a given pathogen flees blood.

Precisely and some state that they have a ongoing infection --- the failure of the PCR test challenges that ---.

Yeah, this would be a dangerous association regardless of the infection being researched. Genes don't cause Lyme disease; a spirochete does.

GWAS identifies genes which increase/decrease risk; in Lyme it seems there was one stand out gene SCGB1D2.
I was actually surprised by the identification of an immune related gene (SCGB1D2) i.e. support for the theory that Lyme is a result of this pathogen(s)

Interesting that it may support the theory that some ME is post infection and/or that Lyme/ME populations cannot be separated accurately. Interesting to see how strong the link between SCGB1D2 & ME, in DecodeME, will be.

Anyway, I found this interesting.

 

[duncan]

Precisely and some state that they have a ongoing infection --- the failure of the PCR test challenges that ---.

But it doesn't, much in the same way that saying we cannot find the spirochete in direct testing in most cases after the bull's-eye doesn't. PCR is a direct test, usually used in blood serology, and Bb flees blood first chance it gets.

GWAS identifies genes which increase/decrease risk; in Lyme it seems there was one stand out gene SCGB1D2.

I don't believe that for a nano-second. This appears to be just a derma-thing that may reduce the tick's likelihood of transmitting Bb, I'm not sure if that qualifies as immune-related.. The competing interest statement is curious, too.

BTW, I like PCR testing, especially in Lyme, it's just very much a hit or miss proposition. And you're right, this can get interesting on many levels.

 

[FMMM1]

But it doesn't, much in the same way that saying we cannot find the spirochete in direct testing in most cases after the bull's-eye doesn't. PCR is a direct test, usually used in blood serology, and Bb flees blood first chance it gets.

Jonathan pointed out that in shingles the dormant virus reactivates --- so would your theory need (est) 1 million people in the EU (+ worldwide) to have Lyme and no cases of reactivation/detection?
EDIT - plus they'd need to test -ve, via PCR, after acute infection has passed.

I don't believe that for a nano-second. This appears to be just a derma-thing that may reduce the tick's likelihood of transmitting Bb, I'm not sure if that qualifies as immune-related.. The competing interest statement is curious, too.

BTW, I like PCR testing, especially in Lyme, it's just very much a hit or miss proposition. And you're right, this can get interesting on many levels.

Difficult to cheat GWAS --- so if something is found then it's of interest --- may be debate about what the gene does, how that relates to mechanism --- is it an artifact, assume tested by further/larger studies

 

[duncan]

Jonathan pointed out that in shingles the dormant virus reactivates --- so would your theory need (est) 1 million people in the EU (+ worldwide) to have Lyme and no cases of reactivation/detection?

I'm sorry, I'm not following you. What theory? Lyme is tissue-tropic. That's not a theory. PCR tests for agents - or their remnants' - DNA, hence it's a direct test of sorts. It's typically employed in serum draws, so the DNA needs to be in the blood. None of that is theory. It may be helpful if you explain your testing 1 million people - I'm not sure what you're asking.

Difficult to cheat GWAS --- so if something is found then it's of interest --- may be debate about what the gene does, how that relates to mechanism --- is it an artifact, assume tested by further/larger studies

If you read the abstract, it appears they are talking about some sort of mechanism that helps prevent the tick from transferring its pathogens in some cases. Maybe I'm misreading that. So while kind of cool, it does not change the equation that Lyme disease is caused by the Bb spirochete, and no gene of which we are aware causes any sort of patient predisposition to Lyme.

I think you may be trying too hard.This is a pathogen-based disease; no genetic contribution is needed to explain it. Bb causes Lyme - unless it's the Swiss Agent, and then we've gone down altogether other rabbit hole. The issues that swirl around Lyme are primarily a) diagnostic (PCR falls under this) and b) therapeutic.

 

[FMMM1]

I think you may be trying too hard.This is a pathogen-based disease; no genetic contribution is needed to explain it. Bb causes Lyme - unless it's the Swiss Agent, and then we've gone down altogether other rabbit hole. The issues that swirl around Lyme are primarily a) diagnostic (PCR falls under this) and b) therapeutic.

I think any disease has genetic element. Simon McGrath posted a while back that a GWAS in migraine identified the (known) key/common pathway. If your theory were correct then the migraine GWAS wouldn't have found anything i.e. since genes are irrelevant to disease---?

I think we may indeed have different views.

I think this vaccination attempt may not be entirely unfounded & the Lyme GWAS seems to me to support a pathogen driver --- I'd like to see the elucidation of the mechanism but I don't think it will be a live/viable (hidden) pathogen.

EDIT - there's actually an interesting mechanism. I.e. in MS EBV infection causes some people to produce autoimmune antibodies to myelin. Something like that, in Lyme, would be really interesting. Immune related genes turn up in MS GWAS - so that type of mechanism would result in (immune) genes turning up in a [Lyme] GWAS - so sort of solvable via GWAS