Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets

Florian Krammer, Rong Hai, Mark Yondola, Gene S. Tan, Victor H. Leyva-Grado, Alex Ryder, Matthew S. Miller, John K. Rose, Peter Palese, Adolfo García-Sastre, Randy A. Albrecht

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model.

Original languageEnglish (US)
Pages (from-to)3432-3442
Number of pages11
JournalJournal of Virology
Volume88
Issue number6
DOIs
StatePublished - Mar 1 2014

Fingerprint

Ferrets
ferrets
Hemagglutinins
hemagglutinins
Orthomyxoviridae
Immunity
immunity
viral load
Influenza Vaccines
Monoclonal Antibodies
monoclonal antibodies
Nose
Vaccination
H1N1 Subtype Influenza A Virus
Turbinates
vaccination
Olfactory Bulb
vaccines
Pandemics
Virus Diseases

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Krammer, F., Hai, R., Yondola, M., Tan, G. S., Leyva-Grado, V. H., Ryder, A., ... Albrecht, R. A. (2014). Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. Journal of Virology, 88(6), 3432-3442. https://doi.org/10.1128/JVI.03004-13

Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. / Krammer, Florian; Hai, Rong; Yondola, Mark; Tan, Gene S.; Leyva-Grado, Victor H.; Ryder, Alex; Miller, Matthew S.; Rose, John K.; Palese, Peter; García-Sastre, Adolfo; Albrecht, Randy A.

In: Journal of Virology, Vol. 88, No. 6, 01.03.2014, p. 3432-3442.

Research output: Contribution to journalArticle

Krammer, F, Hai, R, Yondola, M, Tan, GS, Leyva-Grado, VH, Ryder, A, Miller, MS, Rose, JK, Palese, P, García-Sastre, A & Albrecht, RA 2014, 'Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets', Journal of Virology, vol. 88, no. 6, pp. 3432-3442. https://doi.org/10.1128/JVI.03004-13
Krammer, Florian ; Hai, Rong ; Yondola, Mark ; Tan, Gene S. ; Leyva-Grado, Victor H. ; Ryder, Alex ; Miller, Matthew S. ; Rose, John K. ; Palese, Peter ; García-Sastre, Adolfo ; Albrecht, Randy A. / Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. In: Journal of Virology. 2014 ; Vol. 88, No. 6. pp. 3432-3442.
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