Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

Abstract

Background: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X' . Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim ® ) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim ® creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an "anti-viral state", by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allospecific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/ CTL in circulation capable of responding to the next viral encounter. Conclusion:Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.

Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?

“…The literature on levels and ratio of Th1 and Th2 CD4+ cells and associated cytokine levels in healthy older populations is conflicting. However, most sources report that Th2 responses are upregulated in healthy elderly populations and also predominate in early disease states, which is associated with elderly susceptibility to tuberculosis, influenza, and other infections ( Ponnappan and Ponnappan, 2011 ; Har-Noy and Or, 2020 ). What is troubling with SARS-CoV-2 is that like many viruses, it has evolved mechanisms for evading the host immune system, replicating insidiously ( Har-Noy and Or, 2020 ; Nikolich-Zugich et al, 2020 ).…”

“…However, most sources report that Th2 responses are upregulated in healthy elderly populations and also predominate in early disease states, which is associated with elderly susceptibility to tuberculosis, influenza, and other infections ( Ponnappan and Ponnappan, 2011 ; Har-Noy and Or, 2020 ). What is troubling with SARS-CoV-2 is that like many viruses, it has evolved mechanisms for evading the host immune system, replicating insidiously ( Har-Noy and Or, 2020 ; Nikolich-Zugich et al, 2020 ). This initial Th2 predominance in elderly populations initially aids coronavirus replication until host mechanisms are rapidly overwhelmed by the pathogen and high viral titers ( Har-Noy and Or, 2020 ).…”

“…What is troubling with SARS-CoV-2 is that like many viruses, it has evolved mechanisms for evading the host immune system, replicating insidiously ( Har-Noy and Or, 2020 ; Nikolich-Zugich et al, 2020 ). This initial Th2 predominance in elderly populations initially aids coronavirus replication until host mechanisms are rapidly overwhelmed by the pathogen and high viral titers ( Har-Noy and Or, 2020 ). In response, patients that progress to critical illness, in particular the elderly, are believed to experience a rapid switch to Th1-predominating pathways, overloading the host with inflammatory cytokines that inadvertently harm host tissue ( Ye et al, 2020 ).…”

An Anti-CD6 Monoclonal Antibody (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly Patients

“…Both processes together are suggested as the origin of most of the comorbidities of the elderly and its susceptibility to suffer cancer, chronic in ammatory diseases and new infections [6,7]. The age-associated diseases together with the aging of the structure and function of the lungs increase the likelihood of serious progression of respiratory viral infection [8].…”

An anti-CD6 monoclonal antibody (itolizumab) reduces circulating IL-6 in severe COVID-19 elderly patients

“…Both processes together are suggested as the origin of most of the comorbidities of the elderly and its susceptibility to suffer cancer, chronic in ammatory diseases and new infections [6,7]. The ageassociated diseases together with the aging of the structure and function of the lungs increase the likelihood of serious progression of respiratory viral infection [8].…”