Vaccination with vesicular stomatitis virus-vectored chimeric hemagglutinins protects mice against divergent influenza virus challenge strains

Alex Ryder, Raffael Nachbagauer, Linda Buonocore, Peter Palese, Florian Krammer, John K. Rose

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Seasonal influenza virus infections continue to cause significant disease each year, and there is a constant threat of the emergence of reassortant influenza strains causing a new pandemic. Available influenza vaccines are variably effective each season, are of limited scope at protecting against viruses that have undergone significant antigenic drift, and offer low protection against newly emergent pandemic strains. "Universal" influenza vaccine strategies that focus on the development of humoral immunity directed against the stalk domains of the viral hemagglutinin (HA) show promise for protecting against diverse influenza viruses. Here, we describe such a strategy that utilizes vesicular stomatitis virus (VSV) as a vector for chimeric hemagglutinin (cHA) antigens. This vaccination strategy is effective at generating HA stalk-specific, broadly cross-reactive serum antibodies by both intramuscular and intranasal routes of vaccination. We show that prime-boost vaccination strategies provide protection against both lethal homologous and heterosubtypic influenza challenge and that protection is significantly improved with intranasal vaccine administration. Additionally, we show that vaccination with VSV-cHAs generates greater stalk-specific and cross-reactive serum antibodies than does vaccination with VSV-vectored full-length HAs, confirming that cHA-based vaccination strategies are superior at generating stalk-specific humoral immunity. VSV-vectored influenza vaccines that express chimeric hemagglutinin antigens offer a novel means for protecting against widely diverging influenza viruses.

Original languageEnglish (US)
Pages (from-to)2544-2550
Number of pages7
JournalJournal of Virology
Volume90
Issue number5
DOIs
StatePublished - Jan 1 2016

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Vesiculovirus
Vesicular Stomatitis
Hemagglutinins
hemagglutinins
Orthomyxoviridae
Vaccination
influenza
vaccination
Viruses
Influenza Vaccines
mice
vaccines
Pandemics
pandemic
Humoral Immunity
humoral immunity
Human Influenza
Viral Hemagglutinins
antigens
Antigens

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Vaccination with vesicular stomatitis virus-vectored chimeric hemagglutinins protects mice against divergent influenza virus challenge strains. / Ryder, Alex; Nachbagauer, Raffael; Buonocore, Linda; Palese, Peter; Krammer, Florian; Rose, John K.

In: Journal of Virology, Vol. 90, No. 5, 01.01.2016, p. 2544-2550.

Research output: Contribution to journalArticle

Ryder, Alex ; Nachbagauer, Raffael ; Buonocore, Linda ; Palese, Peter ; Krammer, Florian ; Rose, John K. / Vaccination with vesicular stomatitis virus-vectored chimeric hemagglutinins protects mice against divergent influenza virus challenge strains. In: Journal of Virology. 2016 ; Vol. 90, No. 5. pp. 2544-2550.
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