title: Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination.
abstract: The remarkable infectivity and virulence of the 1918 influenza virus resulted in an unprecedented pandemic, raising the question of whether it is possible to develop protective immunity to this virus and whether immune evasion may have contributed to its spread. Here, we report that the highly lethal 1918 virus is susceptible to immune protection by a preventive vaccine, and we define its mechanism of action. Immunization with plasmid expression vectors encoding hemagglutinin (HA) elicited potent CD4 and CD8 cellular responses as well as neutralizing antibodies. Antibody specificity and titer were defined by a microneutralization and a pseudotype assay that could assess antibody specificity without the need for high-level biocontainment. This pseudotype inhibition assay can define evolving serotypes of influenza viruses and facilitate the development of immune sera and neutralizing monoclonal antibodies that may help contain pandemic influenza. Notably, mice vaccinated with 1918 HA plasmid DNAs showed complete protection to lethal challenge. T cell depletion had no effect on immunity, but passive transfer of purified IgG from anti-H1(1918) immunized mice provided protective immunity for naïve mice challenged with infectious 1918 virus. Thus, humoral immunity directed at the viral HA can protect against the 1918 pandemic virus.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 4502, Building 40, MSC-3005, 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.forename: Chantelle
authors.initials: C
authors.lastname: Hood
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Wei
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight / Q000276:immunology; D004196:Disease Outbreaks; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control*; D015996:Survival Rate; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA