Pandemics in the last two centuries have been initiated by causal pathogens that include Severe Acute Coronavirus 2 (SARS-CoV-2) and Influenza (e.g., the H1N1 pandemic of 2009). The latter is considered to have initiated two prior pandemics in 1918 and 1977, known as the “Spanish Flu” and “Russian Flu”, respectively. Here, we discuss other emerging infections that could be potential public health threats. These include Henipaviruses, which are members of the family Paramyxoviridae that infect bats and other mammals. Paramyxoviridae also include Parainfluenza and Mumps viruses (Rubulavirus) but also Respiratory Syncytial virus (RSV) (Pneumovirus). Additionally included is the Measles virus, recorded for the first time in writing in 1657 (Morbillivirus). In humans and animals, these may cause encephalitis or respiratory diseases. Recently, two more highly pathogenic class 4 viral pathogens emerged. These were named Hendra Henipavirus (HeV) and Nipah Henipavirus (NiV). Nipah virus is a negative-sense single-stranded ribonucleic acid ((−) ssRNA) virus within the family Paramyxoviridae. There are currently no known therapeutics or treatment regimens licensed as effective in humans, with development ongoing. Nipah virus is a lethal emerging zoonotic disease that has been neglected since its characterization in 1999 until recently. Nipah virus infection occurs predominantly in isolated regions of Malaysia, Bangladesh, and India in small outbreaks. Factors that affect animal–human disease transmission include viral mutation, direct contact, amplifying reservoirs, food, close contact, and host cell mutations. There are different strains of Nipah virus, and small outbreaks in humans limit known research and surveillance on this pathogen. The small size of outbreaks in rural areas is suggestive of low transmission. Person-to-person transmission may occur. The role that zoonotic (animal–human) or host immune system cellular factors perform therefore requires analysis. Mortality estimates for NiV infection range from 38–100% (averaging 58.2% in early 2019). It is therefore critical to outline treatments and prevention for NiV disease in future research. The final stages of the disease severely affect key organ systems, particularly the central nervous system and brain. Therefore, here we clarify the pathogenesis, biochemical mechanisms, and all research in context with known immune cell proteins and genetic factors.

The concept of microbial evolution has become progressively intriguing for the immunological side of scientific research, as the ongoing evolutionary battle between microbial agents and animal immunity, which comprises a set of single-nucleotide polymorphisms (SNPs) for both the microbes and the host organisms by means of adaptation to environmental changes, has started including weak points within the innate host immunity as well. Namely, it was discovered only later in the contemporary era that microbial agents tend to use a method of silencing first and second immune lines as an escaping route toward an abundant distribution of the microbial load without a significant restriction from the host organism at the time. Furthermore, it was discovered that the innate immune system displays visible traits of specificity and memory, and also that the adaptive immune system does contain areas of non-specificity as well, which makes it possible for vaccine-based research efforts to bring a wider inclusion of innate, first-line and second-line immune elements into the overall equation of development and possibly rollout as well, perhaps by using such elements as potential immunising agents as well. Additionally, it is possible for central elements of the adaptive immune system to be treated with major elements of the innate immune system by means of improving their overall function and long-term efficacy against pathogenic agents of potential health concern. Such a context may be adapted for a potential delay or even prophylaxis of HIV-induced AIDS, through the treatment and possibly inoculation of adaptive lymphocytes with a low dose of Type I and Type III Interferon glycoproteins, perhaps in combination with a low dose of protollin, which is a pharmaceutical substance that potentially displays immunostimulatory and immunomodulatory effects that are similar to the ones displayed by Type I and Type III Interferons. The present context may also be adapted for a potential delay in the onset of specific proteinopathies, such as Alzheimer’s Disease and possibly Retinitis Pigmentosa as well. An overall approach as such may help the research area of vaccine development undergo potential updates that will potentially help save even more lives worldwide, through the development and application of a scientific concept known as “United Immune System”, as it may be important to transform the smaller and less direct “road” between natural and adaptive immunity into a broader and more direct “highway” between the two immune departments. Such a clinical application may be combined with potential fresh updates into pathogen-derived vaccine development, by using inactivated or completely lysed microbial genomes either lacking the genes encoding microbial proteins with suppressive effects against the host innate immune system, or containing such genes as the only activated microbial genes, to stimulate the host immune system to build novel evolutionary pathways and particularly adapt to changes in the microbial genome that affect the innate immune system, such as the expression of Type I and Type III Interferons.

Artificial intelligence has sharply and broadly evolved since the invention of the computer and its eventual widespread distribution throughout the world. It has led to the replacement of traditional, long-term clinical practices to computerised procedures bringing rapid results. Ultimately, this led to the development of bioinformatics, helping geneticists sequence whole genomes and proteomes within a short time frame. Subsequently, biostatisticians receive novel tools to rapidly build statistical projections in a record amount of time as well. The overall key word behind computerised advancement of biological, genetic and medical research is “time”, as bioinformatics and biotechnology represent two key “enzymes” for the “chemical reaction” of clinical research. As a result, the field of epidemiology has received a novel, all-time opportunity to rapidly build statistical projections regarding the probability of future epidemic or even pandemic outbreaks, and the scope of the current paper is to academically raise awareness of such an opportunity, and to briefly describe examples through which such process could be performed from a general, biomedical science-based perspective. The central scope of the such research efforts could be the investigation of past single-nucleotide polymorphism events that have occurred in certain polymorphic viral agents responsible for the onset of clinically powerful infectious diseases, both indirectly, through the suppression of first-line and second-line host immunity, as well as directly, through the causation of clinical disease and even decrease in the quality of the induced third-line immune activity, to bring an overall system of scientific projection that will bring above-threshold levels of accuracy in the calculation of statistical probabilities regarding the onset of future epidemics and pandemics. It is important to observe the manner microbial agents substantially contribute to the onset of significant and severe clinical infectious diseases, not only by directly inducing the disease and targeting the central, adaptive elements of the host immune system, but also by causing a transient delay in the activation of the peripheral, innate elements of the host immunity, which play a critical role in the creation of an optimal bridge of signalling to the adaptive immunity, meaning that an optimal innate immune activation process plays a crucial role in a timely and qualitative activation of the adaptive immune system.

Transmissible microbial agents have brought utmost short-term and long-term concern for the public health sector due to the fact that they are generally highly capable of inducing serious consequences for the integrity of whole host organisms. Recently, it was discovered that the most important reason of their increasing capability and complexity of their immunopathogenesis capabilities represents their increased abilities of evading host immunity by undergoing direct and indirect levels of molecular self-camouflaging against host Pattern-Recognition Receptor, as well as the Type I and Type III Interferon-encoding genes. Clinical researchers developed medical approaches based on fairly low dosages of Type I Interferons for prophylactic and early therapeutic purposes against major infectious diseases like SARS-CoV-2-induced COVID-19, and the results were rather promising. Furthermore, scientists detected a high extent of immunostimulatory and immunomodulatory effects that such interferon glycoproteins bring upon the rest of the immune system. Essentially, they play a foundational role in the adequate activation of the immune system if they are produced in a timely manner. A developed medical approach against Diabetes Mellitus involving the exponential increase of the bioavailability of insulin via gene insertion into genomes of bacteria inoffensive to human and animal health may constitute a highly-matching model for the development of revolutionary vaccine candidates. Specifically, it may be important to consider the existence of candidate prophylactic and early therapeutic approaches implicating the allowance of environmental spread genetically-modified transmissible microbes with inserted human or animal Type I and/or Type III Interferon-encoding, as well as Pattern Recognition Receptor agonist protein-encoding genes that are attenuated on their genetic side responsible for induced pathogenesis and maintained pathophysiology, and perhaps not as much on their genetic side responsible for microbial reproduction and transmission. Perhaps, human and animal genes encoding recently-discovered fourth class of interferon glycoprotein can also be included in the equation of microbial gene insertion. Other genes that may also be included in such a context are the ones encoding bacterial outer membrane proteins that assemble the protollin immunostimulatory agent together with bacterial lipopolysaccharides, given that protollin plays a major role in the activation of various Pattern Recognition Receptors that are known as Toll-Like Receptors and could likewise count as a Pattern Recognition Receptor agonist. In cases where there is a significant antagonistic activity against the host interferon system, at least some of the microbial genes encoding proteins with such functions may also be functionally attenuated and/or even eliminated from the microbial genome. An overall approach as such ought to occur during the first days of the autumn season, when common cold- and flu-inducing viruses only begin to spread from person to person. Moreover, a number of adenoviral vector-based prophylactic and early therapeutic vaccine candidates against infectious diseases of public health concern that may include HIV-1-induced AIDS could themselves also have such Interferon- and Pattern Recognition Receptor agonist protein-encoding genes inserted into their genome, and such a process could constitute another potential method of extensive immune preparation via a sharped sensitisation of the host cells’ interferon system. It is currently uncertain if HIV-1 genomes themselves could be transformed into self-replicating microbial factories for major natural immune elements, though such a hypothesis should not be ignored. The overall objective of such candidate approaches would be to thoroughly fill in the gap of immune evasion, which may only be possible if Type I and Type III Interferons are automatically produced and signalled to neighbouring cells and tissues by the exact time the first cells become infected. If such a candidate approach is proven to be successful, it would indicate that several pathogenic agents would start undergoing a “Reverse Evolutionary” process that could ultimately even result in their natural de-selection, due to the fact that strategic allowances of such microbes to spread in the local environments would lead to the domination of such genetically-modified microbes against wild-type microbes, and also due to the fact that the human interferon systems would become increasingly sensitised and be situated in a novel evolutionary curve of growth in relation to such microbial agents. In short, following extensive scientific and clinical research efforts, it may now be possible to create and evaluate transmissible vaccine candidates that aim to create a firm bridge between innate and adaptive immunity and that could bring widespread and unprecedentedly beneficial effects for human and animal health on a long-term basis.

The vaccine industry has undoubtedly contributed massively in the medical world, with hundreds of millions of lives saved as a result of the successful development of prophylactic and therapeutic vaccines against various infectious and oncological diseases. Simultaneously, there has been an ongoing evolutionary battle between polymorphic microbes and the human immune system, and various microbes have developed counter-responses against the human host immune system, by creating diverse “holes” of vulnerability in the innate immune system. Such mechanisms may have resulted due to the lower prophylactic and therapeutic focus upon sharpening the innate immune lines as directly as necessary. The overall objective of vaccine-development should be the sharpening of all immune departments that are targeted by various microbial agents for the purpose of transient innate immune suppression and the distribution of the microbial count/load at a systemic level. Likewise, it could be viable for the clinical research community to start focusing upon filling in the “gaps” of vulnerability that are now present in the pathways responsible for the proper natural immune activation and proportionate signalling toward the adaptive immune system. Perhaps, through such a process, the “road” toward the adaptive immune system, which is “old” and filled with “holes”, could be gradually transformed into a perfectly uniform “highway”, with all the required signals transmitted robustly from the innate to the adaptive immune system, before microbes manage to translate the various pathogenic proteins that transiently prevent such transmission altogether, until it becomes too late for the immune response to possibly develop in a proportionate and non-harmful manner to the organism. The potential “missing piece of puzzle” in vaccine-based clinical research could involve training of the human organism to develop immune memory without the host organism reaching a threshold of clinical disease onset even if viruses translate proteins that silence the host interferon system and make it unable to trace produced toxins whilst not directly causing clinical pathophysiology. Whilst it is realistically almost impossible to train the human immune system to develop responses and memory against viral proteins that do not directly cause immunopathology, there could be a set of clinical approaches involving a stimulation for more robust activation of the host interferon system, with an example of such stimuli being the same principal elements of the interferon system. Another example of pharmaceutical approaches would involve the development of drug-like components to target such viral proteins, though they would be more costly and consequently more restricted in usage; due to the fact that viruses are obligate intracellular, particle-based parasites and can only synthesise their proteins inside host cells. Such a scenario would be possible, given that it is almost impossible for human evolutionary growth to eventually stall and not risk experiencing a decrease as a result. Simultaneously, it is important for human society to bind by the principles of maintaining a healthy and nature-friendly lifestyle, given the philosophical quote of “We are what we eat.” The overall objective should be the facilitation of human and animal immune evolution over viral and bacterial molecular self-camouflaging from all possible directions, perhaps by transferring a concept called “a United Immune System” into clinical practice, as a sharper human and animal evolutionary growth resulting from such actions could “cost” the sharper evolutionary growth of microbes as such, given that evolutionary patterns are based upon the models observed in Physics, in Newton’s Third Law of Motion, as well as in the First Law of Thermodynamics, which concerns the Conservation of Energy.

Degenerative proteinopathies constitute a set of molecular diseases that are caused by the misfolding of specific proteins, leading them to change their biochemical configuration and become toxic for entire systems of organs. Such protein toxicity induces the lysing of an increasing number of proteins that have a biochemically ‘wild-type’ version, gradually and eventually leading to a complete shift in the ratio between such ‘wild-type’ and ‘altered’ versions of such proteins, which directly precedes the clinical onset of such diseases. Proteinopathies not only involve neurodegenerative illnesses, but also a disease that leads to a progressive rate of blindness. Sadly, all such impairments that are neurodegenerative in nature may only receive palliative treatment, given that they are caused by aggregated proteins that start damaging and destroying entire neuronal systems, which leads to impairments in the neuro-muscular and ultimately to the inability of the patients to perform vital functions, like breathing and deglutition. There is neither a cure, nor a definitive method in which the progression of the illness can be stopped at the present time. Consequently, all neurodegenerative diseases have mortality rates of 100% and clinical approaches aim to reduce the suffering of such patients. Nonetheless, there seems to be a glimmer of hope regarding future prophylactic approaches that could delay the onset of many types of proteinopathies. Namely, an immune application could support efforts of clinical suffering delay and attenuation in an unprecedented manner. At the same time, it is necessary to emphasise upon realistic scenarios, that it remains virtually impossible to delay the onset of proteinopathies to the point of the patient reaching the average number of years in life expectancy without experiencing clinical symptoms yet. Initially, clinicians developed and tested a nasal spray containing a substance known as protollin, which stimulates a restricted extent of adaptive lymphocyte recruitment and transport to the central nervous system areas affected by initial stages of protein aggregation, activating a substantial number of microglial cells and preventing the lysis of numerous astrocytes, which in turn start lysing a number of beta-amyloid protein aggregates together without inducing pathophysiology, given the stage in which the patients have not experienced any clinical manifestation of the neurodegenerative disease yet. In case of an unsuccessful attempt to bring protollin above the threshold levels of clinical safety and efficacy, an immunostimulatory and immunomodulatory substance containing a low concentration of a mixture of recombinant Type I & III Interferons, innate and adaptive lymphocytes, perhaps themselves priorly treated with such IFN glycoproteins, would probably remain a vital candidate for an effective, yet probably still restricted delay of onset of various proteinopathies that could be neurodegenerative and optically degenerative. An existent success rate of the clinical test allows the opening of a window of opportunity regarding an increased efficacy of such adaptive lymphocyte approach, by including recombinant Type I and Type III Interferons into such a nasal spray, which could also enter adaptive lymphocyte and further improve their structural integrity and their multi-lateral functionality. Moreover, a low dose of protollin, Type I Interferons and Type III Interferons could be inserted in combination into adaptive T-Lymphocytes to optimise their defence mechanisms and immune functions, potentially bringing a considerable immunising effect against microbial diseases like HIV-induced, retroviral AIDS. Such an approach could create a stable and wide “highway bridge” of connection between innate and adaptive immunity, aiming for the best version of an immune contribution toward a considerable delay of proteinopathy clinical onset. Overall, there may be a requirement for a bi-lateral update of immunological research covering therapeutics and vaccine development; an immune system based optimisation that builds a stable and wide bridge of connection more directly between pre-cytokine and post-cytokine immune activation, and overall between innate and adaptive immune departments; and a pathogen-based optimisation that either eliminates or partially activates genes suppressive of Type I and Type III Interferon-encoding genes, helping enliven the concept of “United Immune System” as well, though less directly than the immune system-based potential approach.