title: Activation of cross-reactive mucosal T and B cell responses in human nasopharynx-associated lymphoid tissue in vitro by Modified Vaccinia Ankara-vectored influenza vaccines.
abstract: Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1) (MVA-NP-M1) or pandemic H1N1 HA (MVA-pdmH1HA). The MVA vaccine uptake and expression, and T and B cell responses were analyzed. MVA-vectored vaccines were highly efficient infecting NALT and vaccine antigens were highly expressed by B cells. MVA-NP-M1 elicited T cell response with greater numbers of IFNγ-producing CD4+ T cells and tissue-resident memory T cells than controls. MVA-pdmH1HA induced cross-reactive anti-HA antibodies to a number of influenza subtypes, in an age-dependent manner. The cross-reactive antibodies include anti-avian H5N1 and mainly target HA2 domain.
  
  
  CONCLUSIONS
  MVA vaccines are efficient in infecting NALT and the vaccine antigen is highly expressed by B cells. MVA vaccines expressing conserved influenza antigens induce cross-reactive T and B cell responses in human NALT in vitro, suggesting the potential as mucosal vaccines for broader immunity against influenza.
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mullin
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Muhammed S
authors.initials: MS
authors.lastname: Ahmed
authors.affiliation: ENT Department, Alder Hey Children's Hospital, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sharma
authors.affiliation: ENT Department, Alder Hey Children's Hospital, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Upile
authors.affiliation: ENT Department, Alder Hey Children's Hospital, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Beer
authors.affiliation: ENT Department, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK.
authors.forename: Priya
authors.initials: P
authors.lastname: Achar
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Suttida
authors.initials: S
authors.lastname: Puksuriwong
authors.affiliation: Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Temperton
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: McNamara
authors.affiliation: The Jenner Institute, University of Oxford, ORCRB, Oxford, UK.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lambe
authors.affiliation: The Jenner Institute, University of Oxford, ORCRB, Oxford, UK.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK. Electronic address: qibo.zhang@liv.ac.uk.
authors.forename: Qibo
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D006801:Humans; D018928:Immunity, Mucosal; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D009305:Nasopharynx / Q000276:immunology; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins; D014066:Palatine Tonsil / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014616:Vaccinia virus; D014758:Viral Core Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins
keywords: Antibody response; Children and adults; Influenza vaccine; MVA-vectored vaccine; Mucosal immunity; Nasopharynx-associated lymphoid tissue (NALT)