title: M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection.
abstract: Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-Adrestricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection. Indeed, immunized IL-17A-/-mice were significantly less well protected compared with wild-type mice despite exhibiting comparable antibody levels. Similarly, poor protection was also observed in congenic Balb/B (H-2b) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69+CD103lowM2e-specific memory CD4 T cells were αβ TCR+and 50% were Th17 cells that were associated with an early influx of neutrophils after virus challenge. Adoptively transferred M2e memory CD4 T cells were strong helper T cells, which accelerated M2e- but more importantly also hemagglutinin-specific IgG production. Thus, for the first time we demonstrate that M2e-specific memory CD4 T cells are broadly protective.
authors.affiliation: Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: D G
authors.initials: DG
authors.lastname: Eliasson
authors.affiliation: Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Omokanye
authors.affiliation: Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Schön
authors.affiliation: Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: U A
authors.initials: UA
authors.lastname: Wenzel
authors.affiliation: Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Bernasconi
authors.affiliation: Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bemark
authors.affiliation: Medical Biotechnology Center, VIB and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Kolpe
authors.affiliation: Medical Biotechnology Center, VIB and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: El Bakkouri
authors.affiliation: Medical Biotechnology Center, VIB and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Ysenbaert
authors.affiliation: Medical Biotechnology Center, VIB and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Deng
authors.affiliation: Medical Biotechnology Center, VIB and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Fiers
authors.affiliation: Medical Biotechnology Center, VIB and Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: X
authors.initials: X
authors.lastname: Saelens
authors.affiliation: Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Lycke
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006825:Hybridomas; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011485:Protein Binding; D000072417:Protein Domains / Q000235:genetics; D014611:Vaccination; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D020381:Interleukin-17; D014763:Viral Matrix Proteins