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UNLABELLED: 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. CONCLUSION: 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.

Original publication

DOI

10.1016/j.vaccine.2016.02.028

Type

Journal article

Journal

Vaccine

Publication Date

29/03/2016

Volume

34

Pages

1688 - 1695

Keywords

Antibody response, Children and adults, Influenza vaccine, MVA-vectored vaccine, Mucosal immunity, Nasopharynx-associated lymphoid tissue (NALT), Adolescent, Adult, Antibodies, Viral, B-Lymphocytes, Cells, Cultured, Child, Child, Preschool, Cross Reactions, Humans, Immunity, Mucosal, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A Virus, H5N1 Subtype, Influenza Vaccines, Leukocytes, Mononuclear, Lymphoid Tissue, Nasopharynx, Neutralization Tests, Palatine Tonsil, RNA-Binding Proteins, Recombinant Proteins, T-Lymphocytes, Vaccinia virus, Viral Core Proteins, Viral Matrix Proteins, Young Adult