title: Lipopeptide vaccines illustrate the potential role of subtype-crossreactive T cells in the control of highly virulent influenza.
abstract: BACKGROUND
  The best form of protection against influenza is high-titred virus-neutralizing antibody specific for the challenge strain. However, this is not always possible to achieve by vaccination due to the need for predicting the emerging virus, whether it be a drift variant of existing human endemic influenza type A subtypes or the next pandemic virus, for incorporation into the vaccine. By activating additional arms of the immune system to provide heterosubtypic immunity, that is immunity active against all viruses of type A influenza regardless of subtype or strain, it should be possible to provide significant benefit in situations where appropriate antibody responses are not achieved. Although current inactivated vaccines are unable to induce heterosubtypic CD8(+) T cell immunity, we have shown that lipopeptides are particularly efficient in this regard.
  
  
  OBJECTIVE
  To examine the role of vaccine-induced CD8(+) T cells in altering the course of disease due to highly virulent H1N1 influenza virus in the mouse model.
  
  
  METHODS
  The induction of influenza-specific CD8(+) T cells following intranasal inoculation with lipopeptide vaccine was assessed by intracellular cytokine staining (ICS) and the capacity of these cells to reduce viral loads in the lungs and to protect against death after viral challenge was determined.
  
  
  CONCLUSIONS
  We show that CD8(+) T cells are induced by a single intranasal vaccination with lipopeptide, they remain at substantial levels in the lungs and are efficiently boosted upon challenge with virulent virus to provide late control of pulmonary viral loads. Vaccinated mice are not only protected from death but remain active, indicative of less severe disease despite significant weight loss.
authors.affiliation: The Department of Microbiology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Wy Ching
authors.initials: WC
authors.lastname: Ng
authors.forename: Brad
authors.initials: B
authors.lastname: Gilbertson
authors.forename: Bock
authors.initials: B
authors.lastname: Lim
authors.forename: Weiguang
authors.initials: W
authors.lastname: Zeng
authors.forename: David C
authors.initials: DC
authors.lastname: Jackson
authors.forename: Lorena E
authors.initials: LE
authors.lastname: Brown
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001835:Body Weight; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D055666:Lipopeptides / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D007252:Influenza Vaccines; D055666:Lipopeptides