Understanding the Mode of Action of Several Active Ingredients from the Micro-Immunotherapy Medicine 2LZONA®

Camille Jacques,1 Flora Marchand,2 Mathias Chatelais,2 Adrien Brulefert,3 Ilaria Floris1 1Preclinical Research Department, Labo’life France, Moncoutant-Sur-Sevre, 79320, France; 2ProfileHIT, Sainte-Pazanne, 44680, France; 3QIMA Life Sciences, Gençay, 86160, FranceCorrespondence: Camille Jacques, Preclinical Research Department, Labo’life France, Pescalis-Les Magnys, Moncoutant-sur-Sevre, 79320, France, Email [email protected]: Varicella-zoster virus (VZV) affects over 90% of the global population. The initial encounter with VZV, often in the early years of childhood, results in varicella. From latency, VZV can reactivate in later stages of life, leading to the development of herpes zoster. Considering the importance of host immune responses in preventing reactivation and clinical manifestations associated with VZV infection, a therapy that sustains the immune system could be of great interest.Objective: The present work aimed to set the basis of the possible mode of action of 2LZONA®, a micro-immunotherapy medicine composed of five different capsules. Thus, the effects of several active substances employed in this medicine were assessed in human primary immune-related cells.Results and Discussion: Our results showed that DNA (8 CH) and RNA (8 CH), two active substances used in 2LZONA, displayed phagocytosis-enhancing capabilities in granulocytes and contained sub-micron particles that could explain, at least partially, the observed effect. These two active substances tested singularly and together with other actives of 2LZONA’s capsules, modulated the proliferation of immature, transitory, and mature subsets of natural killer (NK) cells in an IL-15-like pattern, suggesting an enhancement of their activation levels. Moreover, the tested items of 2LZONA increased the secretion of IL-2, IL-6, IL-13, and TNF-α in human peripheral blood mononuclear cells (PBMCs). Furthermore, the proliferation of PBMCs-derived NK cells, intermediate monocytes, and neutrophils was slightly increased by this treatment. In CD3 and CD3/CD28 pre-primed conditions, actives present in one capsule of 2LZONA enhanced the secretion of IL-6 and TNF-α. Finally, one capsule of 2LZONA reduced the expression of human leukocyte antigen (HLA) in IFN-inflamed endothelial cells. Overall, these data provide, for the first time, preliminary experimental evidence of the mechanisms of action of some of the active ingredients employed in 2LZONA capsules.Keywords: varicella-zoster virus, herpes zoster, immune system, cytokines, low doses, ultra-low doses