Airway Memory CD4 + T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

Abstract

SUMMARY Two zoonotic coronaviruses (CoV), SARS-CoV and MERS-CoV have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4+ T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4+ T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was interferon-γ-dependent and required early induction of robust innate and virus-specific CD8+ T cell responses. The conserved epitope was also recognized in SARS-CoV and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4+ T cells targeting conserved epitopes may have broad applicability in the context of new CoV and other respiratory virus outbreaks.

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

“…The same researchers then developed VRP‐MERS‐N vaccine that is based on the N epitope analogue from MERS‐CoV, and similar results were obtained. The depletion of airway CD4 + T cells or inhibition of airway IFN‐γ significantly decreased the protection of VRP‐MERS‐N . This, in addition to the fact that the N epitope is a weak CD8 + T‐cell epitope, supports the role and importance of airway CD4 + T cells in controlling MERS‐CoV infection as well as in vaccine development.…”

“…VRP‐SARS‐N induced airway CD4 + T cells that were able to activate dendritic cell migration to lymph nodes, which in turn stimulated epitope‐specific cytotoxic CD8 + T cells. This resulted in the complete protection of vaccinated mice, immunized in prime boost regimen . The same researchers then developed VRP‐MERS‐N vaccine that is based on the N epitope analogue from MERS‐CoV, and similar results were obtained.…”

Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches

“…While B-cell deficient mice were able to clear MERS-CoV, those lacking T-cells failed to eliminate the virus, pointing out the crucial role of T-cells in viral clearance [26]. This is supported by the observation that T-cells were able to protect aged mice against SARS-CoV infection [27 ] and the fact that a reduced Tcell count was associated with enhanced disease severity in SARS patients [28]. Along with other studies, these data highlight the importance of T-cells for virus clearance and protection against MERS-CoV [26,27 ] and SARS-CoV [29,30].…”

Machine Learning, COVID‐19 (2019‐nCoV), and multi‐OMICS

“…Image cytometry methods and bead‐based flow cytometry methods are at hand to enable for screening and detecting antibody virus interactions and detect viral antigens. Airway memory T‐cells and viral E protein mutations have been identified in CoV infections as potential targets for vaccine strategies . Immune responses seem to be indicative of disease severity but more studies are needed to have a practical assay for decision making at hand.…”