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Macrocyclic Lactones, Streptomyces are used in Vaccines
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Macrocyclic Lactones, Streptomyces are used in Vaccines
<div>Compounds similar to Ivermectin are used in vaccines</div>
The use of Streptomyces for immunization against mycobacterial infections
Abstract
Tuberculosis is one of the leading causes of mortality produced by an infectious agent. Different strategies including bioinformatics are currently being tested to identify and improve vaccines against tuberculosis. Comparative genome analysis between Streptomyces coelicolor and Mycobacterium tuberculosis suggest that both descend from a common Actinomycete ancestor. In this work, we suggest the use of Streptomyces as a live vector and explore the capacity of Streptomyces immunization to induce a protective response against mycobacterial infection. First, we compared the theoretical proteomes of S. coelicolor A3(2) with those of M. tuberculosis H37Rv and Mycobacterium bovis AF2122/97. This study showed a high similarity at the level of individual genes sequences with both bacteria sharing several membrane proteins. Then, we administered Streptomyces intraperitoneally to mice and determined its distribution by histopathology and culture; we did not find systemic dissemination. After administration of Streptomyces through different routes, we identified the most immunogenic, inducing strong humoral response, as denoted by the high serum antibody titers against this organism with cross reactivity to mycobacterial antigens. Finally, we evaluated the level of protection elicited by the inoculation of Streptomyces in Balb/c mice challenged with BCG. In these animals, lung bacillary loads were significantly lower than the control non-sensitized group.. These observations, along with Streptomyces’ potential for expressing foreign proteins, suggest that Streptomyces could be an advantageous vector in the design of new tuberculosis vaccines.
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including in COVID-19 vaccines…read below
Mountain Valley MD to Include Testing of South African Mutation in Upcoming COVID-19 BSL-4 Clearance Work
“TORONTO, Feb. 22, 2021 /CNW/ – Mountain Valley MD Holdings Inc. (the “Company” or “MVMD”) (CSE: MVMD) (FRA: 20MP) (OTCQB: MVMDF) is pleased to announce that it will be testing the new B.1.351 South African COVID-19 variant in its upcoming Bio Safety Level 4 (“BSL-4”) lab study, which is analyzing viral clearance efficacy with the Company’s new solubilized Ivermectin technology.”
markets.businessinsider.com
TORONTO, Feb. 22, 2021 /CNW/ - Mountain Valley MD Holdings Inc. (the 'Company' or 'MVMD') (CSE: MVMD) (FRA: 20MP) (OTCQB: MVMDF) is pleased to ann...
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<div>Another article describing the use of poisonous pesticides in vaccines…</div>
“<b style=”font-family: inherit; font-size: inherit; color: var(–bb-body-text-color);”>RNA, good for vaccines, can also be used as a pesticide”
“R<small>ibonucleic acid (rna),</small> once little-known outside biological circles, has recently become the molecule <em style=”background-color: var(–bb-content-background-color); font-family: inherit; font-size: inherit; color: var(–bb-body-text-color);”>de nos jours. The reason is its role in covid-19 vaccines. The <small style=”background-color: var(–bb-content-background-color); font-family: inherit; color: var(–bb-body-text-color);”>rna</small> molecules in these encode spike, a coronavirus protein. So, when the protein-making machinery of a body cell encounters such <small style=”background-color: var(–bb-content-background-color); font-family: inherit; color: var(–bb-body-text-color);”>rna</small>, spike is what it makes. That lets a vaccine-recipient’s immune system learn to recognise a crucial part of the enemy before the real thing turns up.
Helping to make proteins is not, however, <small>rna</small>’s only job. Among many other things it is central to a process called <small>rna</small> interference, which prevents, rather than facilitates, the manufacture of specific proteins. <small>rna</small>i, as this activity is called for short, has also been investigated medically. It has been approved for use against four genetic diseases and is under investigation for the treatment of more than a dozen others. That is good. Some biologists, though, think <small>rna</small>i may have an important non-medical use as well, as a precisely targeted, environmentally friendly pesticide.
The theory is simple. Identify a protein crucial to the survival of the pest in question. Tailor a specific interfering <small>rna</small> molecule to sabotage production of that protein. Deliver it into the bodies of the pests. Then wait for them all to die. In practice, of course, things are more complicated. Delivery mechanisms have to be designed and regulatory hoops jumped through. But until recently, the biggest obstacle was cost. Life-saving medicines can be expensive. Pesticides must be cheap. One effect of all the medical <small>rna</small> work, however, has been to bring down the cost of making the stuff. As Michael Helmstetter, the boss of <small>rna</small>issance Ag, a firm in Kansas which is developing <small>rna</small>-based pesticides, observes, “a gram of <small>rna</small> cost $100,000 when we started. By 2014 it was $100 a gram. Now it’s a dollar a gram.”
Running interference
Top of the list of potential beneficiaries are honeybees. These semi-domesticated insects, important not only for their eponymous product, but also as pollinators, are plagued by Varroa destructor, a mite a couple of millimetres across (pictured above, on the head of a pupating bee). Varroa mites live by attaching themselves to, and feeding on, bees. This weakens or kills the hosts and also spreads viruses around a hive. Some suspect Varroa plays a role in colony-collapse disorder, a mysterious phenomenon in which most of a hive’s workers desert for no apparent reason.
Beekeepers have tried all sorts of ways of attacking Varroa mites. Some place plastic strips laced with amitraz, a pesticide reckoned particularly effective against mites, at the entrances to hives. Others vaporise oxalic acid, which has a similar reputation, and pump it into the hive. Others still run breeding programmes, selecting for bees that resist infestation. None has succeeded in solving the Varroa problem. At best, these approaches keep the mites’ numbers just below the threshold of crisis.
GreenLight Biosciences, a company in Boston, wants to help. It has bought from Bayer, a German pharmaceutical and life-science firm, the rights to an experimental Varroa pesticide based on <small>rna</small>i. Andrey Zarur, GreenLight’s boss, hopes this will succeed where other methods fail because it attacks the mite in a way mere chemical interventions cannot.
Varroa’s lifecycle starts when a pregnant female mite crawls alongside a bee larva developing inside one of the nursery cells in a hive’s honeycomb. While the larva is growing, this mite just sits there. But once it turns into a pupa she springs into action and lays her eggs on it. Mites and bee then mature in unison over the next few days, and when the adult bee emerges from the cell, the mites attached to it spread around the hive to repeat their trick with future generations.
That the mites spend so much time hidden in the honeycomb makes them hard to attack. And this is where GreenLight hopes its <small>rna</small> will win through. In field trials in the state of Georgia the firm’s operatives are feeding Varroa-destroying <small>rna</small> to the bees themselves—mixing it in sugar water which the workers drink and make honey from. This lays a biotechnological trap for the mites by lacing any honey in their birthplace with the stuff. By lowering the cost of <small>rna</small> production and so allowing much more of it to be used, Mr Zarur thinks he can deliver more <small>rna</small> to the mites, succeeding where Bayer and others did not.
Varroa mites are not, though, the only pests in GreenLight’s crosshairs. It also has its sights trained on Colorado potato beetles, which can devastate crops if not controlled. In their case the <small>rna</small> is simply sprayed onto an infested field and the beetles munch it up. And, though it is cagey about the details, the firm says it has 13 other hostile organisms under investigation, too. These include the fall armyworm, a moth caterpillar that chomps through everything from tobacco to oranges, and the caterpillars of the diamondback moth, the world’s worst pest of brassicas, a group which includes cabbages, cauliflowers, broccoli, Brussels sprouts and oilseed rape. Nor is the <small>rna</small>i approach limited to attacking animals. In principle, any organism is susceptible to it. GreenLight’s target list therefore also includes crop-damaging fungi such as Botrytis, Fusarium and powdery mildew.
Cell game
Not surprisingly, GreenLight has rivals in its quest to develop RNA pesticides. At least two other American companies are working on them as well. AgroSpheres, in Charlottesville, Virginia, is going after diamondback moths. RNAissance Ag, Dr Helmstetter’s firm, is gunning for them too, and also the fall armyworm. All three enterprises think they can make RNA cheaply enough for it to be sprayed onto fields. But they do so in different ways.
GreenLight employs a process called cell-free biology, which is more akin to chemistry than conventional biotechnology. Eliminating the need to coddle fussy micro-organisms, says Mr Zarur, simplifies and cheapens things dramatically. But the more traditional approach taken by <small>rna</small>issance and AgroSpheres, of growing their <small>rna</small> molecules inside modified bacteria, offers advantages, too. Packaging the <small>rna</small> in bacterial cells in this way protects the molecules. It also allows the companies’ biotechnologists to add features to the cell walls, such as stickiness that stops them slipping off the leaves of plants.
Spraying <small>rna</small> onto crops is not, however, the only way to get it into pests. Though it has abandoned its honeybee technology, Bayer is developing a genetically modified maize which produces <small>rna</small> that kills beetle larvae called corn rootworms. A group at the University of Florida is taking a similar approach to the insects known as psyllids that spread a bacterium which causes citrus-greening disease, a serious threat to orange groves.
<small>rna</small> spraying has advantages, though. A farmer can use it on existing crops, rather than having to replant with transgenic versions. The regulations are less onerous than for the creation of transgenic organisms. And in Europe, where transgenic crops are banned in many places, governments seem open to <small>rna</small>-based pesticides.
Andreas Vilcinskas, an entomologist at the Fraunhofer Institute’s campus in Giessen, Germany, who is working with GreenLight, says the German government now supports their development. It has good reason to. In 2018 the European Union banned the outdoor use of three types of neonicotinoids, a popular class of pesticides. Since then, Germany, France and Poland have all had to reverse this ban on an emergency basis after aphids spread like wildfire. Ironically, neonicotinoids were banned to help bees. Promoting <small>rna</small> as a pesticide might thus, as it were, kill many bugs with one stone. ■7
Correction: AgroSpheres is developing a pesticide to tackle diamondback moths, not potato beetles as we first said. Sorry.
A version of this article was published online on May 19th, 2021
This article appeared in the Science & technology section of the print edition under the headline “Debugging. A new approach”
Source: https://archive.is/YFlkL
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