Related Experiment Video
Updated: May 13, 2026
10:39
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
An Influenza Virus M2 Protein Specific Chimeric Antigen Receptor Modulates Influenza A/WSN/33 H1N1 Infection In Vivo.
Simon J Talbot1, Natalie F Blair, Niolette McGill
1University of Edinburgh, Division of Pathway Medicine, Chancellors building, Little France, Edinburgh EH16 4SB, UK.
The Open Virology Journal
|March 16, 2013
Summary
Researchers engineered T-cell receptors, known as chimeric antigen receptors (CARs), to target the M2 protein on influenza A-infected cells. This immunotherapy approach showed promise in reducing viral load in a mouse model, supporting M2e as a universal vaccine target.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- Influenza A virus poses a significant public health threat, necessitating universal vaccine strategies.
- The M2 protein, specifically its extracellular domain (M2e), is a conserved target for developing broad-spectrum influenza vaccines.
- Current influenza vaccines primarily target the highly variable hemagglutinin (HA) protein, limiting their effectiveness against drifted strains.
Purpose of the Study:
- To engineer novel chimeric antigen receptors (CARs) targeting the M2 ectodomain (M2e) of Influenza A.
- To evaluate the in vitro specificity and effector function of M2e-specific CARs.
- To assess the in vivo efficacy of M2e-specific CARs in a murine model of Influenza A infection.
Main Methods:
- Generation of M2-specific CARs by fusing M2-specific antibody sequences with T-cell receptor (TCR) signaling domains.
- In vitro validation using Jurkat T-cells and peripheral blood mononuclear cells (PBMCs) stimulated with M2-specific peptides and M2-expressing cell lines.
- In vivo assessment in a BALB/c murine model infected with Influenza A/WSN/33, monitoring viral titers and CAR-expressing splenocyte presence in the lungs.
Main Results:
- Engineered M2-specific CARs successfully recognized M2-expressing cells and peptides in vitro.
- CAR-expressing T-cells (Jurkat and PBMCs) demonstrated antigen-specific activation, indicated by NFAT upregulation and interferon-gamma production.
- In vivo, M2 CAR-expressing splenocytes were detected in the lungs of infected mice, correlating with a temporary reduction in viral load.
Conclusions:
- M2e-specific CARs represent a viable strategy for MHC-independent targeting of influenza A-infected cells.
- This CAR-based immunotherapy shows potential for controlling influenza A viral replication.
- The M2 ectodomain is a promising target for developing cell-mediated immunotherapies and universal influenza vaccines.
Related Concept Videos
01:27Influenza
Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
02:28Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...