The previous pages in this website describe a number of specific points which now need to be assembled into a larger, cohesive structure or system:

          (1) Nearly all pathogens have evolved in ways that enable them to attack and invade mucosal membranes, and they are (by far) the most important and numerous class of pathogens on this planet;

          (2) The internal immune system simply is not designed, equipped, or suited, to deal with pathogens that can reproduce – usually, very rapidly – entirely within a single cell, in the outermost surface layer of a mucous membrane;

          (3) Therefore, to help fight off such pathogens, vertebrate animals evolved with "mucosal immune systems" that function independently of the internal defenses, and use secreted mucosal IgA antibody dimers which are very different from internal IgG antibodies, in both shape and function;

          (4) There are more than twice as many mucosal antibodies, in just the few pounds of secreted mucosal fluids in a healthy aduilt, than all of the internal antibodies in the entire remaining weight and bulk of that person; and,

          (5) The huge number of secreted mucosal antibodies is powerful and even compelling evidence that mucosal antibodies are hugely important, and valuable, in fighting off mucosal pathogens.

 

          All five of those points directly support an entirely logical conclusion: if any types of vaccines could trigger the creation of good and effective secreted mucosal antibodies, those vaccines (and the antibodies they would help create) could be very useful, and helpful, against numerous different types of pathogens (especially pathogens that attack the "upper respiratory tract", such as influenza, COVID, and "common cold" viruses).

          However, the sad and troubling fact is that, under the "prior art" (i.e., before the scientific community becomes aware of "MALT-targeting" vaccines), there are almost no "really good" mucosal vaccines; and, there is almost no research currently being done on mucosal vaccines, because the only types of "adjuvants" which can make them work potently, in test animals, are too dangerous, and too toxic, to allow the results of any such research to be transferred over, to possible use in humans.

          Here are four facts that can help illustrate, and explain, the limited and inadequate status of mucosal vaccines, prior to any announcements about MALT-targeting vaccines.

          1. Even though there are hundreds (or thousands, depending on how different strains and variants are classified) of different mucosal pathogens, a recent review article dedicated entirely to mucosal vaccines (Rhee et al, “Mucosal vaccine adjuvants update,” Clin Exp Vaccine Res 1: 50-63 (2012)) listed all of the commercially available human mucosal vaccines that the authors could find information about. However, that listing took less than a single paragraph, and it didn’t even merit a table, to list them.
         2. The so-called “FluMist” vaccine, which is administered via a nasal spray, usually reaches only about 30 to 40% efficacy, each year. Those numbers mean that 60 to 70% of the people who get that vaccine, still become infected by serious cases of influenza, each year, despite being vaccinated by it.
         3. The most recent attempt to create a new nasally-delivered vaccine occurred in Switzerland, where a mucosal influenza vaccine was put into human use. However, even though it had performed well in animal tests, it ended up causing some of the human recipients to suffer a neurologic affliction called “Bell’s palsy,” which creates a partial paralysis of the facial muscles, usually on either the left or the right side of the face. As such, it can lead to strange, unsettling, sometimes bizarre, and in some cases grotesque and genuinely frightening facial expressions, among sufferers. That vaccine had to be withdrawn from the market when those cases began to appear, and the manufacturer was driven out of business, by the costs of the liabilities it was facing. That event is well and widely known, among vaccine experts, and it powerfully discourages any companies or researchers that might otherwise be tempted to launch an expensive research project into any other potential mucosal vaccine, no matter how promising it might be.
         4. It appears that the only mucosal vaccine which has actually been commercialized for human use, since the year 2000, is an orally-ingested vaccine against "rotaviruses" (which create severe digestive problems among infants, in tropical regions). However, the first attempt to release that vaccine led to major problems, and that first version had to be withdrawn, after it began causing a severe and potentially fatal intestinal problem called “intussusception” – which must be corrected surgically, as quickly as possible – in some of the infants who received that vaccine. The sponsoring company re-designed and re-tooled that vaccine, by reducing the number of rotavirus antigens the virus particles carried (which presumably made it somewhat less effective). It is now being sold under the trademark ROTA-TEQ (TM).

​          More information to support and explain the facts listed above (and which further discusses the severe inadequacies of currently-available mucosal vaccines) is contained in the "Background Section" of a pending (but not yet published) patent application, which can  be downloaded via this button: 

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          Accordingly, mucosal vaccines simply are not being actively and successfully developed, for human use; and, vaccines which are injected almost never lead to mucosal antibody formation. That has created a huge and unmet need, for better methods for creating, not just vaccines that can be APPLIED topically to mucous membranes, but which will actively trigger the formation of secreted mucosal antibodies, when applied in that manner.

          However, based on everything we have seen so far, in the tests we have done to date, and based on what we know about how M cells, dendritic cells, and MALT patches function, we believe and assert that mucosal vaccines with large numbers of a selected antigen, and small numbers of potent MALT-targeting sequences, can trigger and drive the formation of BOTH: (i)  internal IgG antibodies, AND, (ii) secreted mucosal IgA dimers, which will bind – tightly, and selectively – to pathogens which have those antigen sequences on their surfaces.

          THAT claim (i.e., as stated directly above) is being made with a very high level of confidence, based on "antibody production tests" that have been completed to date. In absolutely every animal tested to date – in which their saliva and blood samples were tested for both internal IgG antibodies in blood, and secreted IgA antibodies in saliva, using both ELISA tests, and SDS/PAGE-Western blot tests – a single nasal infusion of droplets containing (filamentous Inovirus) phage particles carrying both a MALT-targeting transport sequence (in low numbers), and a well-known and easily tested antigen sequence (the HA-tag epitope sequence, in large numbers), triggered the "robust" formation of both secreted IgA dimers in saliva, and internal IgG antibodies in blood serum.

          As this is being written, we do not yet know how they will perform, in "pathogen challenge tests", because we are still awaiting the delivery of the first batches of phages that  will allow us to perform those tests. That first batch of phage particles wil contain engineered T7 phages, carrying about 400 copies/particle of the FI-6 antigen from influenza, described in the NIH's Epitope Database at www.iedb.org/epitope/162644, and carrying about 40 copies of the MALT-targeting sequences we selected for the first "antibody production" tests.

          Even though we do not yet know the results of the pathogen challenge tests, we feel fully justified in stating that every immunologist, every vaccine research team, every vaccine company, the faculty and students at every veterinary school, and every federal or state agency that has any active interest in vaccines, should at least become aware of the MALT-targeting approach to designing vaccines, and should begin learning, now, about the science, the logic, the reasoning, and the immune cell activities that have supported and guided this work so far. Regardless of whether the results from the first sets of pathogen challenge tests show positive results, or whether they point out how many problems still need to be solved before MALT-targeting vaccines can become practical and approved for use in animals such as poultry, pets, or livestock, the simple fact is that if more people, and more companies, become interested and involved in this research, sooner rather than later, the benefits and cost savings will begin appearing sooner, rather than later.

          So, we do not make the following three predictions as confident claims, but as reasons why people who are already working with vaccines should become interested in, and aware of, the "MALT-targeting transport peptide" options that can be used to improve mucosal vaccines. Based on everything we have seen, learned, and shown to date, we hope and believe that the first two predictions below will be proven in animal usage, and will become reliably "do-able", within the next five years:

          1. Mucosal vaccines carrying MALT-targeting sequences will be shown to be fully capable of triggering and driving the formation of, not just internal IgG antibodies, but also, “secreted mucosal IgA antibody dimers”; and, since they can provide a balanced, bi-functional, "two-handed" immune response – both internally, and in mucosal secretions – these vaccines will be able to provide better protection than any other vaccines that are available as this is being written . . . especially against upper respiratory tract infections.

          2. Mucosal vaccines carrying MALT-targeting sequences will be shown to be capable of eliminating any need for using the types of inflammatory and irritating "adjuvants" which, today, are used to make injected vaccines more effective. As mentioned on a prior page, most "adjuvants" work by causing muscle cells, at the site of an injection, to rapidly begin sending out distress signals (cytokines), which will recruit nearby mobile immune cells to come to the site of the injection as quickly as possible, before the vaccine particles can be diluted, diffused, or degraded. Accordingly, we believe MALT-targeting mucosal vaccines will end up creating a new generation, and a new era, of vaccines and vaccine technology, which might be called "Post-Adjuvant Vaccines", and/or "Precision-Guided Vaccines".

          3. In addition to the two predictions above, which can be established by vaccines in non-human animals, we also predict that, when MALT-targeting mucosal vaccines become available for human use, they will be able to eliminate any need for injections, needles, and the types of hazardous and dangerous medical wastes that are created when needles are used. Instead, "preferred" modes of inoculation are likely to become social events, in which bowls of lollipops (with vaccine particles embedded in a hard-candy matrix) are passed around, by nurses or even just administrators, at places like senior centers, community centers, schools, churches, walk-in clinics, drugstores, offices and other workplaces, etc.; and, we also predict that usage and inoculation rates will increase, by substantial and possibly large ("very large"?) percentages, when compared to COVID vaccination levels in the early 2020s.

          Among other advantages, candy-flavored lollipops, on "sticks", can be sucked until halfway dissolved, and then placed in some type of small, simple, convenient storage device for several hours, to provide enough time for newly-activated dendritic cells get "saddled up" and leave their M cell docking sites, and to then allow a "new crop" of immature dendritic cells to locate and settle into the M-cell docking sites that were vacated when the "first wave" of dendritic cells became activated, and left those docking sites. In other words, a simple "lollipop or lozenge" delivery system can provide a "sustained release" mode of administration, which can be substantially more effective than a "one-time, single-shot" dosage.

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