title: Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza A virus that expresses an altered nucleoprotein sequence.
abstract: Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes.
authors.affiliation: Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Health, Denver, Colorado, United States of America. megan.macleod@glasgow.ac.uk
authors.forename: Megan K L
authors.initials: MK
authors.lastname: Macleod
authors.forename: Alexandria
authors.initials: A
authors.lastname: David
authors.forename: Niyun
authors.initials: N
authors.lastname: Jin
authors.forename: Laura
authors.initials: L
authors.lastname: Noges
authors.forename: Jieru
authors.initials: J
authors.lastname: Wang
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D009698:Nucleoproteins