Turning Pathogens into Vaccines via Loss-of-Function Research and Interferon Gene Insertion: Trampling Death by Death?
Authors: Carp Theodor-Nicolae 
Published: January 2025

Throughout several centuries, infectious pathogenic agents have been used as models for the ongoing efforts of vaccine development, which saved hundreds of millions of lives from life-threatening infectious diseases worldwide. Nonetheless, there has been a missing gap that various polymorphic microbes have been taking advantage of in their evolutionary pathway: the interferon system, which often prevented the timely activation of second and third-line host immunity, leading to chaotic and mismatching immune responses. The phenomenon of increased incubation period of various infectious diseases may be a result of the increased abilities of such microbial agents to directly and indirectly undergo molecular self-camouflaging, which prevents the activation of Type I and Type III Interferon-encoding genes (INGs) in indirect and direct manners respectively, and cleaves the mRNA molecules encoding such interferon glycoproteins, often causing major delays in the process of autocrine and paracrine signalling of Type I and Type III Interferon glycoproteins, which in turn allows an unrestricted, exponential increase of the microbial load/count, giving rise to a statistical probability that the quality of the delayed immune response will be low and contributory to the processes of pathogenesis and pathophysiology. Apprehending the foundational layer of the current problems in evolutionary microbiology, epidemiology and public health studies is most likely crucial for the course of immunological, pharmaceutical and vaccine-related clinical research. In the current case, it is the complex set of molecular capabilities to suppress Type I and Type III Interferon-based signalling displayed by several polymorphic microbes of public health concern, and it may be that the rates of immunopathogenesis induced by such microbes are directly proportional with such pathogenic abilities of induced interferon suppression. Proportional medical responses could include the development of approaches involving low dosages of human recombinant Type I and Type III Interferon glycoprotein and perhaps also of protollin in the nasopharyngeal cavity, potentially bringing an example of putting a novel concept of a “United Immune System” into practice. Furthermore, similar dosages of such interferons could be administered into human immune cells including plasmacytoid dendritic cells, as well as natural and adaptive lymphocytes, to optimise their immune function and integrity against various environmental hazards. Ultimately, clinical researchers may isolate the pathogenic agents, attenuate them through the process of loss-of-function laboratory research, before performing gene editing to insert Type I and Type III Interferon-encoding, perhaps as well as Pattern Recognition Receptor (PRR) Agonist-encoding genes that specifically match the PRR targeted by the implicated microbes, into their genomic profile and potentially releasing the genetically-modified pathogens back into the environment transmissible factories of Type I and Type III Interferons, perhaps as well as of specific PRR Agonist proteins. Such a change may bring various pathogenic agents into a path of evolutionary self-destruction, as they would start producing and sending signals to the proximal, innate immune system as soon as they enter the first host cells, making their same processes of induced innate immune suppression ineffective, and several dilemmas in microbial evolution could ultimately be tackled as a result, possibly even at least attenuating the phenomenon of acquired antibiotic resistance by various pathogenic bacteria. A clinical approach as such is likely based on the model of increasing the accessibility to insulin-based treatment against Diabetes Mellitus via insulin-encoding gene insertion into the genomes of harmless bacteria prior to their administration into human host organisms, which saved millions of lives worldwide. Processes of shrinkage of any level of limitations to potential efficacy would include the manual utilisation of inhalators, oral drops and/or injectable serums containing such modified microbes to ensure that such an immunising effect would be conferred simultaneously with exposure to the artificially-changed genetic version of the microbe. A set of clinical responses involving all such pathways may ultimately bring a promise of a health-related “Golden Age” throughout the world.