THE SCIENCE
Harness the Intelligence of your Immune System
Antiviral Immunotherapy, Fighting Fire with Fire
A New Paradigm for Treatment of COVID-19 Infections
Viruses like SARS-CoV-2, the causative agent of COVID-19 infections, require a living host to survive and reproduce. All viruses evolved as obligate intracellular parasites that infect host cells and utilize the host cell genetic machinery to reproduce themselves. The viral life-cycle may produce no major clinical effects, but in some cases, a severe infection may ensue with death of the host as the final outcome. However, the host is not without capabilities of defending itself, and thus the presence of viruses has led to the evolution of a diverse array of antiviral mechanisms. Most notable is the antiviral immune response that has evolved to recognize invading viruses as foreign and dangerous, and to interrupt the viral life-cycle and eliminate the virus threat.
The first line of immune defense against virus infection is the innate antiviral immune response. This response is mediated by various molecules and cells (e.g. interferons and NK cells) that immediately work to defend against virus infection. The innate immune mechanisms act quickly and often eliminate the invading virus, but when the virus is highly virulent or introduced in high amounts, innate antiviral immunity may be overwhelmed. The second line of defense is the adaptive immune response (e.g., viral neutralizing antibodies and CD8 cytotoxic T cells), and while highly specific and potent, it requires several days to attain protective levels. During this critical time the innate immune response, even if insufficient to eliminate the invading virus, holds the virus infection in check to give the adaptive response time to mature.
Most viruses, upon infection of a host cell, induce the production and secretion of interferons (molecules that “interfere” with viral growth). The secreted interferons signal back on the infected host cell (autocrine signaling) and induce the expression of interferon-stimulated genes (ISGs) that code for hundreds of antiviral molecules. Even more importantly, the interferons produced by the infected cells bind to adjacent non-infected cells and bring these cells to an antiviral state (paracrine signaling). The secreted interferons can also distribute widely in the body and confer a systemic antiviral immunity (endocrine signaling). While interferons do not directly kill viruses, they orchestrate an antiviral state in host cells that prevents the viruses from spreading.
While the adaptive immune response is noted for its diversity of pathogen recognition molecules, and the extraordinary specificity for targeting pathogens, the innate immune response is much more limited in both diversity and specificity. On the surface this may appear to be disadvantageous, but closer examination reveals an ingenious defense strategy that can be applied to a multitude of viruses. For instance, if the invading virus is the influenza virus, recognition by generic host cell receptors will stimulate the interferon response that will engage a series of antiviral mechanisms leading to inhibition of virus growth. If the invading virus is a Herpes virus, it will be recognized by different receptors on host cells but the same interferon response will inhibit viral growth. This allows a common defense mechanism to be applied to many viruses.
That brings us to the notion of Immunacor's antiviral-immunotherapy, an animal derived inactivated virus. When injected intramuscularly, various immune cells (e.g., plasmacytoid dendritic cells) to produce a broad spectrum antiviral response that includes production and secretion of Types I, II, and III interferons. These interferons are secreted into the blood within hours and bind to interferon receptors present on the surface of most nucleated cells in the human body. This binding stimulates several intracellular signaling pathways that, among other functions, activate the expression of the ISGs and confer on target cells an antiviral refractory state.
The general concept is to use Immunacor's antiviral immunotherapy to augment the innate immune response to broad spectrum of virus infections, it may play an even more critical role in infections cause by viruses that normally inhibit the interferon response. Numbered among the many viruses that have evolved mechanisms to subvert the innate interferon response is SARS-CoV-2. Like the earlier versions of the serious disease-causing coronaviruses (SARS and MERS), SARS-CoV-2 greatly inhibits the production of interferons via ORF3b. The result of this is failure of paracrine interferon signaling to adjacent non-infected epithelial cells and spread of the virus. However, IMNC-101 can be used to stimulate a systemic interferon response that cannot be blocked by SARS-CoV-2. Administration in an early COVID-19 infection should stimulate an interferon response that brings host cells to an antiviral state and slows or prevents spread of the virus. The success metric would be COVID-19 patients that have milder disease of shorter duration and decreased hospitalizations. It may seem counterintuitive to use a virus to treat a virus infection, but it fits the notion of “fighting fire with fire”.