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Front Immunol ; 11: 575074, 2020.
Article in English | MEDLINE | ID: covidwho-1256374

ABSTRACT

Combined cellular and humoral host immune response determine the clinical course of a viral infection and effectiveness of vaccination, but currently the cellular immune response cannot be measured on simple blood samples. As functional activity of immune cells is determined by coordinated activity of signaling pathways, we developed mRNA-based JAK-STAT signaling pathway activity assays to quantitatively measure the cellular immune response on Affymetrix expression microarray data of various types of blood samples from virally infected patients (influenza, RSV, dengue, yellow fever, rotavirus) or vaccinated individuals, and to determine vaccine immunogenicity. JAK-STAT1/2 pathway activity was increased in blood samples of patients with viral, but not bacterial, infection and was higher in influenza compared to RSV-infected patients, reflecting known differences in immunogenicity. High JAK-STAT3 pathway activity was associated with more severe RSV infection. In contrast to inactivated influenza virus vaccine, live yellow fever vaccine did induce JAK-STAT1/2 pathway activity in blood samples, indicating superior immunogenicity. Normal (healthy) JAK-STAT1/2 pathway activity was established, enabling assay interpretation without the need for a reference sample. The JAK-STAT pathway assays enable measurement of cellular immune response for prognosis, therapy stratification, vaccine development, and clinical testing.


Subject(s)
Dengue Virus/immunology , Immunity, Cellular , Orthomyxoviridae/immunology , Respiratory Syncytial Virus, Human/immunology , Rotavirus/immunology , Viral Vaccines/therapeutic use , Virus Diseases/immunology , Yellow fever virus/immunology , Biomarkers/blood , Dengue/blood , Dengue/immunology , Dengue/prevention & control , Dengue/virology , Dengue Vaccines/therapeutic use , Dengue Virus/pathogenicity , Diagnosis, Differential , Host-Pathogen Interactions , Humans , Immunogenicity, Vaccine , Influenza Vaccines/therapeutic use , Influenza, Human/blood , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Oligonucleotide Array Sequence Analysis , Orthomyxoviridae/pathogenicity , Predictive Value of Tests , RNA, Messenger/blood , RNA, Messenger/genetics , Respiratory Syncytial Virus Infections/blood , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/pathogenicity , Rotavirus/pathogenicity , Rotavirus Infections/blood , Rotavirus Infections/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Rotavirus Vaccines , Signal Transduction/genetics , Virus Diseases/blood , Virus Diseases/prevention & control , Virus Diseases/virology , Yellow Fever/blood , Yellow Fever/immunology , Yellow Fever/prevention & control , Yellow Fever/virology , Yellow Fever Vaccine/therapeutic use , Yellow fever virus/pathogenicity
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