Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination

Wing Pui Kong, Chantelle Hood, Zhi Yong Yang, Chih Jen Wei, Ling Xu, Adolfo García-Sastre, Terrence M. Tumpey, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)15987-15991
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number43
DOIs
StatePublished - Oct 24 2006
Externally publishedYes

Keywords

  • Influenza vaccines
  • Neutralizing antibody
  • Vaccines

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination'. Together they form a unique fingerprint.

Cite this