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» LymeNet Flash » Questions and Discussion » Medical Questions » OspA , and the bizarre world of R Dattwyler

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Author Topic: OspA , and the bizarre world of R Dattwyler
Eight Legs Bad
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Is anyone as bewildered as I am by the proposal for an oral Osp A based Lyme vaccine which the notorious Dattwyler published a few months ago?

Ref-"Oral immunization with recombinant Lactobacillus plantarum induces a protective immune response in the Lyme disease mouse model" , del Rio et al, Clin. Vaccine Immunol. doi:10.1128/CVI.00169-08 published online July 2008)

Throughout the paper, which describes trials of a vaccine administered intragastrically and also orally to mice, Dattwyler and his colleagues emphasise how important it is to use these routes, rather than the parenteral route. It is absolutely essential, they say, to induce mucosal immunity. But why?

The vaccine consists of a commensal Lactobacillus strain harbouring recombinant OspA. Now let's remember that we were all told that the Osp A vaccines work by destroying OspA-expressing borrelia ***in the tick***.

Not in the blood, and certainly not in the mucous membrane, but ***in the midgut of the tick***.

So why then do we need a vaccine delivery method designed to induce mucosal, as opposed to systemic, immunity?

A patent published this year by Dattwyler seems to explain it. He describes a method in which the commensal Lactobacillus is transformed with a gene sequence for Borrelial OspA combined with virulence factors from Yersinia pestis, the agent of plague.

He then claims that you could use the same method to genetically hook almost any antigen, from any pathogen at all, onto borrelial OspA, express your recombinant creation in the harmless Lactobacillus, and produce vaccines and cures that way.

He champions, in this patent, his method as being ideal not only for vaccinating against plague, and against Lyme itself, but also against a whole range of other bacterial diseases, viral diseases including AIDS, fungal infections, protozoal and even worm infestations.

He goes into some detail in some of his writings about how easy it is to administer oral vaccines, how much more acceptable it is to the public, how you could do it quickly en masse if necessary, how you would not need trained personnel and could do it in "resource-poor" environments.

All well and good. We could assume so far that Dattwyler is just anxious to protect poor people in the developing world from plague, Lyme, HIV or whatever.

But somehow I don't think so.

With plague and the other well-known bioweapons, the likelihood is that a victim would be exposed by the airborne route. So it is easy to see that a vaccine that produced antibodies in the respiratory mucosa would be invaluable.

And with AIDS, the value of a strong localised immunity in the genital mucous membrane is obvious.

But why is mucosal immunity to OspA needed in humans to be protected from Lyme?

If the whole point, (as Dattwyler himself re-iterates), of an OspA vaccine is to destroy Bb ***in the tick***, during the actual process of the tick feeding on a human being, why the burning need to have an active anti-OspA immune response in the lining of our larynx, gut, lungs, vagina or rectum? Let's face it, we don't really expect ticks to be crawling into any of those places (let's hope!)

Dattwyler concludes his July 2008 paper on the oral vaccine with these words:

"We report the development of an oral, live vaccine delivery vehicle based on a
bacteria 'generally regarded as safe' by the FDA. Our method of expressing vaccine
antigens in L. plantarum induces both systemic and mucosal immunity after oral
administration.

"Standard parenteral vaccines do not induce mucosal immunity and the
failure to do so has led to vaccine failures even in the face of strong systemic immunity.

"Our platform technology, in addition to the effective oral vaccine that is described for
Lyme disease, can be expanded upon and applied to design oral vaccines against
several microbial pathogens and possibly, some allergens.

"Some examples of potential
mucosal vaccines include targets to Y. pestis, B. anthracis and F. tularensis. These
airborne, Category A bioterrorism agents would greatly benefit from a mucosal and
systemic double-edged immune response."

So, if the real point of inventing the new Lyme vaccine was not to prevent Lyme, but to showcase a method for preventing aerosolised nasties, why use Lyme's OspA as the vaccine target?

An antigen expressed almost exclusively in the midgut of a tick, and "switched off" before the bug enters our bodies via the feeding tick.... we should never expect to meet OspA via the airborne route, nor indeed on any of our mucous membranes.

Or does Dattwyler have other information which he is not sharing?

There are many other strange issues thrown up by Dattwyler's work in this field, but I'll leave it at that for now.

I'd be ineterested to know if anyone else finds all this as puzzling as I do.

Elena

--------------------
Justice will be ours.

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tcw
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A quick search shows quite a few teams experimenting with recombinant L. plantarum (and other Lactobacilli) as vehicles for introducing antigens into hosts. Some experiments have met with more success than others it seems.

My guess is that the mucosal immunity is just a side effect with respect to Bb - it seems like recombinant L. plantarum is a promising vector for vaccine delivery and they want to show that it works to deliver the OspA antigen.

Why OspA is a good question - where is the OspA produced by the recombinant L. plantarum stored - in cytosol? How does the OspA presented to the host in the gut produce systemic immunity? I do not know much about how these things work.

In another thread about PAI-1 I dug up some stuff on OspA that I did not see before - it seems to bind plasminogen in the host and when the bound plasminogen is activated to plasmin the Bb can use it to penetrate epithelial cells.

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bpeck
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I haven't read the paper, but I bet he's trying to patented the oral route of vaccination for these diseases.

Secondly, mucosal entry of a vaccine starts the immune response in a different way (it's complicated) than an injection.

As far as the OspA theory- I think it proposes that if you have antibodies against OspA- your body will neutralize the bacteria from the tick just as the bacteria migrates from the ticks gut to your body.. Normally OspA changes to OsPC very soon after it gets in the body...

He's a weird guy. He's publishing trying to hit a $$ jackpot. Actually there are quite a few researchers racing to patent ANOTHER Lyme vaccine.
Pretty weird for an infection they say is so easily cured with 20 days of abx.

Barb

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oxygenbabe
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I think Barb is right. OspA quickly shifts to OspC in the human and the type of OspC determines virulence/progression.

OspA is so highly immunogenic in humans his work seems risky to me. An OspC vaccine would be a much better idea and someone posted a study on here in beagles using the conserved part of OspC across different borrelia species, immunizing the beagles 100%.

As for the mucosal route--the intestinal lumen absorbs peptides and sends them intact to the blood, so oral vaccines should work (as the polio vaccine for instance).

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Tincup
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Dattwyler! UGGGGGG!!!!

My LEAST favorite of the Bumsterre butt kissing gang! Look what he is up to NOW!!!

If I were wanting to promote a product... anywhere on this planet.. I certainly wouldn't put HIS name on it... or have him involved in any way.

But why is he involved?

You said it all in this one line, 8 legs...

"A patent published this year by Dattwyler seems to explain it."

Yepper...

Cha-ching, cha-ching $$$$$$.

For the life of me I can't figure out why any of the ducks would STAY involved with Lyme anything after all the wrongs they've done!

The ONLY reason ... in MY opinion... is cha-ching $$$.

They should all... as my granny use to say... be boiled in apple butter.

But it would certainly ruin the apple butter now, wouldn't it?

[Eek!]

And darn it all. I gotta laugh.

Several people suggested we all be NICE here on the board as a New Year resolution. I just read their posts. I thought that was real sweet and a GREAT idea... and I would certainly try.

Well, that lasted about 24 seconds!!!

I just can't seem to cozy up to the ducks.... or keep my mouth shut when I see BAD things happening at their hands.

But... the above is my opinion only...

Maybe next year I can learn to keep my big trap shut?

HA!

[Big Grin]

--------------------
www.TreatTheBite.com
www.DrJonesKids.org
www.MarylandLyme.org
www.LymeDoc.org

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adamm
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My goodness. This is terrifying!
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Eight Legs Bad
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quote:
Originally posted by tcw:
...

My guess is that the mucosal immunity is just a side effect with respect to Bb - it seems like recombinant L. plantarum is a promising vector for vaccine delivery and they want to show that it works to deliver the OspA antigen. ...

So in other words what you are saying is that Dattwyler is not really interested in creating an OspA-based vaccine against tick-borne Lyme at all, but only wants to show he can deliver the OspA antigen to the mucosa because OspA is integral to the biowarfare vaccines he is working on, as described in his patent?

Elena

--------------------
Justice will be ours.

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Eight Legs Bad
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quote:
Originally posted by oxygenbabe:


OspA is so highly immunogenic in humans his work seems risky to me.

According to the patent Dattwyler brought out related to this work, the very fact that OspA **is** so immunogenic seems to be exactly why he is interested in it.

It appears he wants to use ospA as an adjuvant in vaccines against plague, tularemia, anthrax etc.. Or at least that's how the patent reads.

Elena

--------------------
Justice will be ours.

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oxygenbabe
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Eight Legs, you may be right. Great. Autoimmune diseases here we come.

I hope this doesn't go anywhere soon.

I know a viable Osp C vaccine was killed through lack of funding which I personally believed was influenced by the Osp A vaccine Bumsteere crowd.

That was years ago.

Now it sounds like OspC is being worked on again.

That's what we NEED. It's OspC that regulated virulence in humans.

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tcw
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quote:
So in other words what you are saying is that Dattwyler is not really interested in creating an OspA-based vaccine against tick-borne Lyme at all, but only wants to show he can deliver the OspA antigen to the mucosa because OspA is integral to the biowarfare vaccines he is working on, as described in his patent?
No, my guess is that OspA is only relevant to existing patents on vaccines. Recombinant L. plantarum is just another delivery method.

I really have no opinion on any relation to biowarfare at all.

I think that any vaccine based on OspA or OspC is probably not going to be all that effective - OspA is less gentically variant than OspC, but is usually repressed where we need vaccines the most, in the human bloodstream. OspC is so variant (21 and counting, maybe more?) that I wonder if a commerically viable vaccine could actually be produced that would provide protection against so many OspC antigens.

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oxygenbabe
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The recent study in beagles used a universally conserved portion of Osp C.

It can be done. In fact when I spoke some years ago with the scientists who had been working on an Osp C vaccine its potential looked excellent.

Politics (Bumsteere Osp A muscling in) backwatered it.

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Eight Legs Bad
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quote:
Originally posted by tcw:
...No, my guess is that OspA is only relevant to existing patents on vaccines. Recombinant L. plantarum is just another delivery method.

I really have no opinion on any relation to biowarfare at all. ...

Sorry tcw, I'm a little bit confused as to what you're saying here. There is an existing 2008 patent by Dattwyler on a vaccine. The vaccine is based on L. plantarum transformed with ospA.

But the ospA has had something else added on to it - the genes for virulence factors from Yersinia pestis, the agent of plague.

Lactobacillus was chosen because of the need to provide ***mucosal*** immunity against plague.

I would say that's a relation to biowarfare, wouldnt you?

Elena

--------------------
Justice will be ours.

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Eight Legs Bad
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Hi again

Just to make things a bit clearer for everyone here, I'll post an extract from Dattwyler's 2008 OspA-based biowarfare vaccine patent. Bear in mind that the "immunogenic polypeptide" he refers to at the beginning is OspA fom Lyme:

"FIELD OF THE INVENTION

The present invention relates, e.g., to a bacterium, such as a Lactobacillus bacterium, which has been recombinantly engineered to express one or more immunogenic polypeptides. The bacterium may be an immunogenic composition, such as a live bacterial vaccine.

BACKGROUND INFORMATION

Yersinia pestis (Y. pestis), the etiologic agent of plague, is a prime candidate to be used as a bioweapon, for example during a terrorist attack.

Whether weaponized or not, this pathogen has attributes that make it an ideal choice to produce mass casualties. An attack with a Y. pestis would undoubtedly be delivered as an aerosol. Pneumonic plague is extremely contagious, highly lethal and there are naturally occurring multiple antibiotic resistant strains.

Only 100 to 500 organisms need to be inhaled to produce pneumonic plague. Post exposure, pneumonia develops within two to three days and it is virtually 100 percent lethal if treatment with efficacious antibiotics is not begun immediately.

In addition, as pneumonia develops the victim becomes an excellent vehicle, rapidly spreading the disease. Coughing produces infected droplets and anyone within a radius of two meters from an individual with pneumonic plague has a high risk of becoming infected themselves.

Thus, once pneumonic plague develops in a population, unless it is identified and dealt with promptly and effectively, the number of cases will increase exponentially. An attack with an antibiotic resistant strain would vastly complicate our response.

One solution is to develop a safe effective vaccine, particularly an oral vaccine, preferably one that can protect against both bubonic and pneumonic plague. Ideally any plague vaccine should produce both a systemic and a mucosal immune response. Currently, there is no plague vaccine licensed in the United States.

The present application describes, e.g., a recombinant bacterial vaccine that can be used against Yersinia pestis, e.g. as an oral vaccine.

The method for making and using the bacterium
can serve as a platform for the development of a variety of vaccines against other pathogens, including other pathogenic bacteria, viruses, fungi or parasites.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows Western blot analysis of Lactobacillus plantarum strain 256 (Lp256) expressing variants of B. burgdorferi OspA: LpA, LpAa, and LpAc 17d. The size of the wild type OspA, shown in relation to markers of 28 and 35 Kd, is about 31 Kd. ...."


Elena

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Justice will be ours.

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Pinelady
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They are all trying to appear stupid to keep from going to jail...

I have never known ignorance to be a cause for mass slaughter such as this.

--------------------
Suspected Lyme 07 Test neg One band migrating in IgG region
unable to identify.Igenex Jan.09IFA titer 1:40 IND
IgM neg pos
31 +++ 34 IND 39 IND 41 IND 83-93 +
DX:Neuroborreliosis

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lou
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If it came from Dattwyler, I would personally expect trouble. And OSP A certainly has a question mark beside it for vaccines.

If they have not yet found all the OSP C types that exist in nature, how can they know what is universally conserved?

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Pinelady
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http://iai.asm.org/cgi/content/abstract/IAI.01274-10v1

Infect. Immun. doi:10.1128/IAI.01274-10
Copyright (c) 2011, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The OspE-related proteins inhibit complement deposition and enhance serum resistance of... Borrelia burgdorferi, the Lyme disease spirochete

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104

Abstract
Borrelia burgdorferi, the Lyme disease spirochete, binds the host complement inhibitors factor H (FH) and FH-like protein 1 (FHL-1).

Binding of FH/FHL-1 by the B. burgdorferi proteins CspA and the OspE-related proteins is thought to enhance resistance to serum-mediated killing.

While previous reports have shown that CspA confers serum resistance in B. burgdorferi,

it is unclear whether

the OspE-related proteins are relevant in B. burgdorferi serum resistance

when OspE is expressed on the borrelial surface.

To assess the role of the OspE-related proteins, we overexpressed the OspE-related proteins


in a serum sensitive CspA mutant strain.


OspE overexpression enhanced serum resistance of the CspA deficient organisms.

Furthermore, FH was more efficiently bound to the B. burgdorferi surface when OspE was overexpressed.

Deposition of complement components C3 and C5b-9 (the membrane attack complex), however, was reduced on the surface of the OspE overexpressing strain as compared to the CspA mutant strain.

These data demonstrate that OspE proteins expressed on the surface of B. burgdorferi bind FH and protect the organism from complement deposition and subsequent serum-mediated destruction.

--------------------
Suspected Lyme 07 Test neg One band migrating in IgG region
unable to identify.Igenex Jan.09IFA titer 1:40 IND
IgM neg pos
31 +++ 34 IND 39 IND 41 IND 83-93 +
DX:Neuroborreliosis

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Pinelady
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As far as I see---nothing can be determined until they determine what else the borrelia is hiding.

For all we know the only difference in the expression is another virus or other organism creating it...

Such as XMRV etc. that has not been elucidated or reference to yet in the proteins expressions..

Who Knows?

--------------------
Suspected Lyme 07 Test neg One band migrating in IgG region
unable to identify.Igenex Jan.09IFA titer 1:40 IND
IgM neg pos
31 +++ 34 IND 39 IND 41 IND 83-93 +
DX:Neuroborreliosis

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