Vaccines represent preventative interventions amenable to immunogenetic prediction of how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can render possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (virus and/or vaccine) could provoke partial, complete or even failed protection for some individuals treated under the same conditions. We review genetic variants and mechanistic relationships among chemokines, chemokine receptors, interleukins, interferons, interferon receptors, toll-like receptors, histocompatibility antigens, various immunoglobulins and major histocompatibility complex antigens. These are the targets for variation among macrophages, dendritic cells, natural killer cells, T-and Blymphocytes, and complement. The technology platforms (mRNA, viral vectors, proteins) utilized to produce vaccines against SARS-CoV-2 infections may each trigger genetically distinct immune reactogenic profiles. With DNA biobanking and immunoprofiling of recipients, global COVID-19 vaccinations could launch a new era of personalized healthcare.

Previous studies of our laboratory have demonstrated that Fh15, the recombinant variant of F. hepatica FABP exhibit powerful anti-inflammatory properties. The administration of a single IV dose (for NHP) or IP dose (for mouse) of Fh15 prior to or after lethal doses of E. coli-LPS, respectively is enough to significantly suppress the pro-inflammatory cytokine storm and prevent the lethal pathologic consequences of septic shock. This suggest that Fh15 has a broad spectrum of action and may modulate pro-inflammatory mechanisms. The present study aimed to identify intracellular inflammatory pathways that could be modulated by Fh15. To achieve this goal, we have applied a quantitative proteomic approach using a Tandem Mass Tag peptide labelling, which has been used to quantified and identified biological macromolecules such as proteins. Samples were analyzed using Liquid Chromatography with tandem mass spectrometry. RAW 264.7 cells were stimulated with LPS and/or Fh15, cells treated with Fh15 or LPS alone were used as control. For the bioinformatics analysis, a fold change of 1.5 and pValue ≤ 0.05, were considered for the enrichment analysis, using the Ingenuity Pathway Analysis. Using these approaches, we identified 257 proteins associated with LPS treatment: 173 were up regulated and 84 were down regulated. Furthermore, we identified 139 proteins associated with Fh15 treatment: 38 were up-regulated and 101 were down-regulated. The IPA analysis identified proteins associated with NFkB, iNOS and Th1/Th2 pathways. We also identified 8 proteins differentially abundant that are associated with inflammatory and/or infectious diseases. Currently we are evaluating these proteins with ELISA, Western Blot and/or Flow cytometry techniques. Supported by 1SC1AI155439-01 NIAID

This article assesses the role of recipient genetics to COVID-19 vaccine responses. Vaccines represent preventative interventions suitable to an immunogenetic perspective to predict how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can make possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (either virus or vaccine) could provoke partial, complete or even failed protection for some individuals treated under the same conditions. We review genetic variants and mechanistic relationships among chemokines, chemokine receptors, interleukins, interferons, interferon receptors, toll-like receptors, histocompatibility antigens, various immunoglobulins and major histocompatibility complex antigens. These are the targets for variation among macrophages, dendritic cells, Natural Killer cells, T- and B- lymphocytes, and complement. The acute nature of vaccine reactogenicity is reminiscent of the time course of adverse drug reaction mediated by the immune system. The variety of technology platforms (mRNA, viral vectors) utilized currently to produce vaccines against SARS-CoV-2 infections may each also trigger genetically distinct immune reactogenic profiles. With biobanking of recipient genomic DNA and serum immunoprofiling, global COVID-19 vaccinations could launch a new era of research and clinical translation in personalized health.

Fasciola hepaticais known to suppresses antigen specific Th1 responses in concurrent bacterial infections while promoting the Th2/Treg regulatory responses. We have recently demonstrated that a single intraperitoneal injection with native F. hepatica glutathione S-transferase (nFhGST) mu-class, can suppresses the cytokine storm and increasing the survival rate in a mouse model of septic shock. Knowing that the peritoneal macrophages play essential roles in the defense against microbial agents, the present study aimed to determine whether nFhGST could modulate the dynamic of these cells. The remarkable findings in this article are, (i) nFhGST suppresses serum IL-12, TNFa, and IFN-g in BALB/c septic mice, whereas concurrently prevent the disappearance of large peritoneal macrophages and significantly increasing this population in the peritoneal cavity of LPS-treated animals, (ii) nFhGST was able to significantly suppresses the high levels of LPS-induced IL-10, which is considered a key cytokine in the pathophysiology of sepsis. (iii) nFhGST suppresses the classical activation of macrophagesin vitroby expressing high levels ofYm-1, a typical M2-type marker, secreting the production of IL-37, and preventing the production of TNFa, iNOS2 and nitric oxide, which are typical markers of M1-type macrophages, (iv) nFhGST suppresses the bacterial phagocytosis of macrophages, thus partially affecting the capacity of macrophages in destroying microbial pathogens. These findings demonstrate that nFhGST that nFhGST is an excellent modulator of the peritoneal macrophages contentin vivo, reinforcing the capacity of nFhGST as an anti-inflammatory drug against sepsis in animal models.