Precision-Guided (MALT-Targeting) Mucosal Vaccines

          That’s an extremely bold claim, so we invite any and all experts to approach it skeptically, and see if they can find any flaws in the path we have identified, or in the steps we are using to explore and travel down that pathway. If you think you have spotted a flaw – or, if you want to contact us, to find out more, and possibly begin to consider whether you might want to get involved in this work, at an early stage – feel free to get in touch with us, via the last page of this website.

          Our approach starts with a simple, basic fact: immune cells, and immune systems, distinguish between “self” particles (which must be tolerated), versus alien and invading “non-self” particles (which must be defended against) by using “receptor proteins” on the surfaces of the immune cells, to analyze proteins on the surfaces of the particles that the immune cells encounter. The details and mechanisms of how immune cells perform that task are extraordinarily complex; however, people don’t need to understand those details, or mechanisms. The simple fact is that immune cells evolved with “receptor proteins” on their surfaces, which enable them to distinguish between “non-self” invaders and pathogens, versus “self” cells (and, they also figured out how to accept and tolerate the benevolent bacteria that enable digestion).

          So, that led to an initial question: would it be possible to create new types of vaccine particles having “transport peptides” attached to their surfaces, which might be able to increase the speed and potency of how those vaccine particles are taken in, and processed in desired ways, by tricking/fooling one or more types of immune cells into "believing" that those vaccine particles actually are highly dangerous and very important pathogens?

          That initial question led to two follow-up questions, which can be phrased as follows:

          1. Which types of immune cells would be the best possible types of immune cells to “target”, if we began looking for ways to create vaccine particles that would be recognized rapidly, pulled in rapidly, and processed – not just rapidly, but also, in desired and useful ways – by those “targeted” immune cells?

          – and –

          2. What would be the best way to identify a set of protein sequences which would be recognized, rapidly and potently, by the “targeted” immune cells, and which would provoke and trigger those “targeted” immune cells to rapidly pull in, and begin processing, vaccine particles carrying those types of “targeted transport proteins” on their surfaces?

          These questions – and the answers we came up with – were first recognized and formulated, not by an immunologist, but by a physiologist. His specialty was in tracking and analyzing where viruses and other foreign particles and molecules travel to, and where they end up (and/or spread to), after they enter the body of a mouse or rat.

          He had been doing that type of work for nearly 30 years, when he realized how “immune-cell-targeting” peptides could be identified, and used. And, as a brief aside, he did not set out to search for ways to “target” immune cells that could create better vaccines. Instead, his primary interest was in neurons, and neurology. After he heard about the complex mixtures called “phage display libraries” – which are explained in more detail HERE – an idea occurred to him, about how he might be able to design a new and innovative type of “screening test” which might be able to isolate those few phage particles, from among millions of candidates in a “phage display library”, which happened to be carrying foreign peptide inserts that could trigger and drive uptake – followed by an unusual type of transport – by the long neuronal fibers that extend out into muscles and limbs, from certain types of neurons which have their main cell bodies and nuclei inside the brain or spinal cord.

          As a very brief summary/digression, he realized that if he packed millions of phage particles around the “sciatic nerve” bundle in the KNEE of a rat, and then figured out how to harvest those few phage particles which had managed to be taken in by those nerve fibers, and then transported upward, to the HIP, he might be on to something. His hope was that if he could isolate and identify “transport peptides” which could trigger and drive intake, by neuronal fibers located outside the so-called “blood-brain barrier” – followed by transport in an unusual direction within those fibers (i.e., toward the main cell body, rather than toward the outer tips of the neuronal fibers) – then, he might be able to create genetic vectors that could deliver highly hormone-like signaling peptides (such as the classic “nerve growth factor”) into brains or spinal cords, in non-invasive ways that would not require any type of invasive surgery, drilling, or injection.

          He did indeed discover such a “neuronal intake and transport” peptide, However, sadly (indeed, tragically), he did not have the right set of skills to adequately create (or, to be able to persuade others to create, and fund) the research that might have been able to convert his initial discovery, into products that could be actually used, to help patients suffering from neuro-degenerative diseases, damage after a stroke, or spinal injury. The person who wrote this page of this website remains convinced – to this day – that that physiologist may have “thought up” the best way that has ever been “thought up”, to treat patients suffering from progressive neuro-degenerative diseases, such as Alzheimer’s or Parkinson’s, or even from stroke damage, spinal injury, or other traumatic events.

          However, merely “thinking up” something is (again, sadly, and even tragically) very, very different from being able to show that it actually works . . . or, from being able to convince others to invest in it, in ways that might be able to show that it might actually work.

          After several years of wrestling unsuccessfully with that profoundly frustrating effort, that physiologist suddenly realized that a completely different type of approach – involving a totally different type of screening test, involving immune cells, rather than neurons – might be able to isolate and identify a different set of “targeted transport peptides” which could drive an entirely different type of response, by certain types of targeted immune cells. And, he realized how those new and different types of transport peptides – if they could be isolated and identified, by the new type of “screening test” which focused on immune cells – might be adapted for use, not with the standard and long-known types of INJECTED vaccines, but with new types of MUCOSAL vaccines.

          So, that is where our story begins . . .

          The next page, in this website, describes a specialized class of lymph nodes, which are mounted in fully-exposed locations, on the outer surfaces of mucosal membranes, in all vertebrate animals. They became one of the major defenses against mucosal pathogens. For complex reasons – which are summarized HERE – mucosal pathogens are (by far) the largest and most important class of pathogens on this planet. Therefore, mucosal pathogens provoked a type of “arms race”, which pitted them against the animals they kept trying to infect. Animals responded to those attacks by developing several defenses, and one of those key defenses became fully-functional lymph nodes which are mounted, in fully exposed locations, on the outer surfaces of the mucosal membranes. In those exposed surface locations, those types of immune cells – located and working inside fully-equipped, fully-functional lymph nodes – can directly contact, and “sample”, and analyze, and pull in, and begin responding immediately to . . . any particles which appear to be dangerous and infective pathogens.

          Another major defensive response led to the creation of an entirely new and different class of antibodies, which are secreted into the saliva, nasal secretions, lung and genital fluids, and digestive juices. As described HERE, secreted mucosal antibodies have totally different structures than the Y-shaped internal antibodies that everyone already knows about; and, they work by an entirely different mechanism, compared to Y-shaped internal antibodies. However, very few people (except among physicians and immunologists) have ever heard anything about those types of secreted mucosal antibodies; and – except among physicians and immunologists – almost no one knows anything about them, or how they function.

          That lack of knowledge becomes even more curious, in view of another curious but crucial fact: THERE ARE MORE THAN TWICE AS MANY SECRETED MUCOSAL ANTIBODIES, IN JUST THE FEW POUNDS OF SALIVA, SNOT, LUNG FLUIDS, AND DIGESTIVE JUICES, IN ANY HEALTHY ADULT HUMAN, THAN ALL OF THE Y-SHAPED INTERNAL ANTIBODIES IN THE ENTIRE REMAINING (AND MUCH, MUCH GREATER) BULK AND WEIGHT OF THAT PERSON.

          Anyone who knows the facts about secreted mucosal antibodies can reasonably assume, and conclude, and “suggest, hypothesize, and postulate,” that the reason almost no one (except for physicians and immunologists) has ever even heard about those types of antibodies – even though they outnumber the Y-shaped internal antibodies by more than 2-to-1  – is because doctors and scientists do NOT like and do NOT want to talk about them, and do NOT want the general public (or, the semi-informed, semi-expert members of various governmental agencies) to know  enough about them to begin asking pointed and unsettling questions, which would begin with phrases such as, “Why can’t we . . . or, more accurately, why can't YOU . . . ?”

          The sad and even tragic fact is that, despite DECADES of effort, by THOUSANDS of skilled researchers, physicians, immunologists, and vaccine companies have NEVER been able to figure out any good way to reliably and consistently create vaccines which can trigger the formation of “secreted mucosal antibodies”, without using highly toxic additives that would never be approved for use in humans.

          But . . . those of us who work with the startup company called “Precision-Guided Vaccines LLC” think that THAT . . . will soon change.

          We think it will be changed – dramatically, and even profoundly – by small protein segments which can be called “MALT-targeting peptides”.

          Those small protein segments ALSO can be called “HYPER-pathogen peptides”. Why? Because they can fool, and trick, and “persuade” certain types of immune cells into “believing” that any small particle which has THOSE peptides, on its surface, is a VERY dangerous, VERY infective, and VERY important pathogen, which poses a major threat of creating a major, severe, and potentially even deadly infection.

          And, therefore, any small particle which has THOSE types of super-alarming HYPER-pathogen peptides, on its surface – which might someday include engineered vaccine particles, in mucosal vaccines – must be responded to, as quickly as possible, by immediately launching an antibody-forming response, against the antigen sequences that will also be present, and fully exposed (and, in MUCH larger numbers), on the surfaces of those vaccine particles.

          Stated in other words, if “HYPER-pathogen peptides” (also called MALT-targeting sequences) are attached (in small numbers) to the surfaces of mucosal vaccine particles, our hope and belief is that those small peptide sequences will function as “targeted transport” peptides, comparable to using 5 locomotive engines to pull a train with 200 loaded freight cars. We hope that those “MALT-targeting” sequences will cause any and all mucosal vaccine particles which have those “HYPER-pathogen” sequences, on their surfaces, to be rapidly taken in – and, rapidly processed, in ways that will lead to antibody-forming responses – by the specialized immune cells that live, dwell, and do their work in the specialized types of lymph nodes that are mounted, and fully exposed, and directly accessible, on the outer surfaces of every type of mucosal membrane, in every type of vertebrate animal.

          Those surface-mounted mucosal lymph nodes are called “MALT patches”, where “MALT” is the acronym for “mucosal-associated lymphoid tissues”. In large animals, MALT patches include the tonsils and adenoids, located near the rear surfaces of the mouth and nasal cavity. In mice and rats, they are located in well-known locations that can be directly accessed, by creating “skull sections” from painlessly-euthanized phage-infused animals. In addition, hundreds of them are distributed along the internal surfaces of the intestines; and, intestinal MALT patches usually are called “Peyer’s patches”.

          So . . . that sets the stage that readers will need to understand, to help them figure out how “MALT-targeting peptides” (aka HYPER-pathogen peptides) appear poised to unlock gates that will lead to an entirely new class of “mucosal vaccines” which will be able to function, for the first time ever, as “precision-guided vaccines”.

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          The next page attempts to introduce and summarize a number of additional factors that need to be, not mastered, but at least somewhat understood, to adequately recognize and understand both: (i) what this invention is, and how it works; and, (ii) how and why we are convinced that it has the potential to make . . . not just "major", but "massive, epochal, generational" changes, in vaccine technology, and vaccine usage. And, that requires understanding at least three major advantages that will become achievable, if "MALT-targeting" transport peptides lead to the world's first-ever "precision-guided vaccines". 

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          The two “PDF” buttons below will enable anyone to download, at no charge: (i) a complete copy of this website, in pdf format; and, (ii) the entire Background section, and list of cited references, from one of several pending (but not-yet-published) patent applications that describe and claim MALT-targeting vaccines, and the methods used to create them.

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