Respiratory syncytial virus (RSV)-specific cell-mediated immune responses in human peripheral blood (VIR2P.1025)

Abstract

Abstract Respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections and hospitalization in infants, but no vaccine exists, primarily because the immune response is poorly understood and immune correlates of protection have not been adequately defined. Antiviral lymphocytes, along with secreted immunoglobulins (Ig) are likely the most important components of effective anti-RSV immunity RSV-specific assays to quantify the effective cell-mediated immune response to naturally-occurring RSV infections are imperative. We therefore quantified IFN-γ secreting human peripheral blood mononuclear cells (PBMCs) with and without stimulation by whole RSV from different clades, and with highly purified RSV-peptide pools. PBMCs from donors demonstrated between-donor variable levels of immune response to the RSV peptide pools and the whole virus preparations. Robust IFN-γ T-cell responses were observed at 72 hours in all PBMCs, thus allowing a single time point assay evaluation. Higher responses were seen in the CD4+ population of PBMCs compared to the CD8+ population. Responses of CD8+ PBMCs to whole virus preparations and to mock infection control preparations were similar and responses to RSV peptide pools were not statistically significant from the negative peptide control. IFN-γ based ELISPOTS and FACS assays are promising tools to quantify RSV-specific T-cell-mediated immune responses in human blood.