T cell immune profiling of respiratory syncytial virus for the development of a targeted immunotherapy

Abstract

SummaryRespiratory syncytial virus (RSV)‐associated viral infections are a major public health problem affecting the immunologically naïve/compromised populations. Given the RSV‐associated morbidity and the limited treatment options, we sought to characterize the cellular immune response to RSV to develop a targeted T cell therapy for off‐the‐shelf administration to immunocompromised individuals. Here we report on the immunological profiling, as well as manufacturing, characterization and antiviral properties of these RSV‐targeted T cells. A randomized, phase 1/2 clinical trial evaluating their safety and activity in haematopoietic stem cell transplant recipients as an off‐the‐shelf multi‐respiratory virus‐directed product is currently underway (NCT04933968, https://clinicaltrials.gov).

Efficacy of budesonide/formoterol inhalation powder in treating viral pneumonia in children

“…Processing and presentation of viral antigens enable lymphocytes to recognize specific receptors, undergo cloning, differentiation and proliferation, thereby generating a specific immune response. During the process of exogenous antigen presentation, a series of degradation, transportation, and binding reactions activate T lymphocytes[ 22 ]. CD3 + , CD4 + and natural killer (NK) cells are the main immune subsets in the body.…”

Reshaping Our Knowledge: Advancements in Understanding the Immune Response to Human Respiratory Syncytial Virus

“…Among those, IL-12 induces the secretion of IFN-γ, which contributes to reducing viral replication and favoring the Th1 cells differentiation ( Figure 3 ) [ 33 ]. A recent preclinical study was conducted with the aim of characterizing the cellular immune response to RSV with the goal of developing a targeted T-cell therapy for convenient administration to immunocompromised individuals [ 93 ]. The study revealed that nucleoprotein N and protein F were the most potent antigens in terms of immunogenicity, leading to the in vitro activation of T cells that specifically recognize the RSV virus (RSV-STs).…”

“…These included the increased expression of molecules associated with degranulation (CD107a), co-stimulation (4-1BB), and activation (CD69) as well as the production of effector cytokines (IFNγ and TNF-α) upon exposure to viral antigens. The expanded RSV-STs were skewed toward a Th1-polarized response, displaying polyfunctional attributes and the ability to selectively target and eliminate HLA-matched antigen-loaded cells [ 93 ].…”