title: A heat-inactivated H7N3 vaccine induces cross-reactive cellular immunity in HLA-A2.1 transgenic mice.
abstract: BACKGROUND
  Cross-reactive immunity against heterologous strains of influenza virus has the potential to provide partial protection in individuals that lack the proper neutralizing antibodies. In particular, the boosting of memory CD8+ T cell responses to conserved viral proteins can attenuate disease severity caused by influenza virus antigenic variants or pandemic strains. However, little is yet known about which of these conserved internal antigens would better induce and/or recall memory CD8+ T cells after in vivo administration of an inactivated whole virus vaccine.
  
  
  METHODS
  We explored the CD8 + T cell responses to selected epitopes of the internal proteins of an H7N3 influenza virus that were cross-reactive with A/PR/8/34 virus in HLA-A2.1 transgenic (AAD) mice.
  
  
  RESULTS
  CD8+ T cells against dominant and subdominant epitopes were detected upon infection of mice with live H7N3 virus, whereas immunization with non-replicating virus elicited CD8+ T cell responses against mostly immunodominant epitopes, which were rapidly recalled following infection with A/PR/8/34 virus. These vaccine-induced T cell responses were able to reduce the lung viral load in mice challenged intranasally with the heterologous influenza virus.
  
  
  CONCLUSIONS
  A single immunization with non-replicating influenza virus vaccines may be able to elicit or recall cross-reactive CD8+ T cell responses to conserved immunodominant epitopes and, to some extent, counteract an infection by heterologous virus.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Mario
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, 00185, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Garulli
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Sciaraffia
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Facchini
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Donatelli
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. mariarita.castrucci@iss.it.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Castrucci
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000378:metabolism; D007111:Immunity, Cellular; D064789:Immunity, Heterologous; D057920:Influenza A Virus, H7N3 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008822:Mice, Transgenic; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated