Human T cells efficiently control RSV infection

Abstract

Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in infants, immunocompromised individuals, and older individuals. There is an urgent need for effective antivirals and vaccines for high-risk individuals. We used 2 complementary in vivo models to analyze RSV-associated human lung pathology and human immune correlates of protection. RSV infection resulted in widespread human lung epithelial damage, a proinflammatory innate immune response, and elicited a natural adaptive human immune response that conferred protective immunity. We demonstrated a key role for human T cells in controlling RSV infection. Specifically, primed human CD8 + T cells or CD4 + T cells effectively and independently control RSV replication in human lung tissue in the absence of an RSV-specific antibody response. These preclinical data support the development of RSV vaccines, which also elicit effective T cell responses to improve RSV vaccine efficacy.

Non-fatal outcomes of COVID-19 disease in pediatric organ transplantation associates with down-regulation of senescence pathways

“…Interestingly, some of the cellular immune effects observed in SARS-CoV-2 infection differ from data reported in other respiratory viral infections; specifically, human CD8 + T cells or CD4 + T cells effectively and independently control RSV replication in human lung tissue in the absence of an RSV-specific antibody response 41 , and both RSV and human metapneumovirus (hMPV) demonstrate a virus-specific and subset-specific effect on myeloid dendritic cell function (mDC) 42 not reported in SARS-CoV-2 infection. To the best of our knowledge there are no published reports detailing cellular immune changes following RSV and hMPV in infants and children with solid organ transplants, as such we are unable to comment on differences between non-transplanted children and children with solid organ transplants.…”

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

“…The role of humoral immunity in developing short-lived protective antibodies is well demonstrated; mediated cell immunity would play pivotal roles in both hRSV clearance and pathogenesis [ 90 ]. Alternatively, recent findings from preclinical studies indicate that CD8 + T cells and CD4 + T cells could proficiently and autonomously manage RSV replication in human lung tissue even in the absence of a specific antibody response against RSV [ 91 ]. An initial transient systemic T-cell lymphopenia occurs during RSV LRTI; the underlying mechanism seems to be virus-induced T-cells apoptosis [ 84 ].…”

“…Preclinical investigations indicate that depleting human CD8 + T cells in mice hampers though does not entirely eradicate the ability to control RSV infection. This implies that CD8 + T cells alone are not the exclusive agents responsible for virus clearance [ 91 ]. Likewise, findings from preclinical studies suggest that CD8 + T cells could also play a role in causing lung damage in humans after being exposed to RSV [ 91 ].…”

“…This implies that CD8 + T cells alone are not the exclusive agents responsible for virus clearance [ 91 ]. Likewise, findings from preclinical studies suggest that CD8 + T cells could also play a role in causing lung damage in humans after being exposed to RSV [ 91 ].…”

A Mixture of T-Cell Epitope Peptides Derived from Human Respiratory Syncytial Virus F Protein Conferred Protection in DR1-TCR Tg Mice

“…Human T-cells are crucial in managing HRSV infection, clearing intracellular pathogens, and maintaining long-lasting immune responses [ 13 , 14 , 15 ]. Moreover, primed human CD8 + T-cells or CD4 + T-cells effectively and independently control HRSV replication in human lung tissue in the absence of an HRSV-specific antibody response [ 16 ]. Consequently, an optimal vaccine can induce both humoral and cellular immunity, thereby eliciting a balanced immune response in the host.…”