Immunologic characterization of a Rhesus Macaque H1N1 challenge model for candidate influenza virus vaccine assessment

Jason A. Skinner, Sandra M. Zurawski, Chie Sugimoto, Heather Vinet-Oliphant, Parvathi Vinod, Yaming Xue, Kasi Russell-Lodrigue, Randy A. Albrecht, Adolfo García-Sastre, Andres M. Salazar, Chad J. Roy, Marcelo J. Kuroda, Sang Kon Oh, Gerard Zurawski

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Despite the availability of annually formulated vaccines, influenza virus infection remains a worldwide public health burden. Therefore, it is important to develop preclinical challenge models that enable the evaluation of vaccine candidates while elucidating mechanisms of protection. Here, we report that naive rhesus macaques challenged with 2009 pandemic H1N1 (pH1N1) influenza virus do not develop observable clinical symptoms of disease but develop a subclinical biphasic fever on days 1 and 5 to 6 postchallenge. Whole blood microarray analysis further revealed that interferon activity was associated with fever. We then tested whether type I interferon activity in the blood is a correlate of vaccine efficacy. The animals immunized with candidate vaccines carrying hemagglutinin (HA) or nucleoprotein (NP) exhibited significantly reduced interferon activity on days 5 to 6 postchallenge. Supported by cellular and serological data, we conclude that blood interferon activity is a prominent marker that provides a convenient metric of influenza virus vaccine efficacy in the subclinical rhesus macaque model.

Original languageEnglish (US)
Pages (from-to)1668-1680
Number of pages13
JournalClinical and Vaccine Immunology
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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    Skinner, J. A., Zurawski, S. M., Sugimoto, C., Vinet-Oliphant, H., Vinod, P., Xue, Y., Russell-Lodrigue, K., Albrecht, R. A., García-Sastre, A., Salazar, A. M., Roy, C. J., Kuroda, M. J., Oh, S. K., & Zurawski, G. (2014). Immunologic characterization of a Rhesus Macaque H1N1 challenge model for candidate influenza virus vaccine assessment. Clinical and Vaccine Immunology, 21(12), 1668-1680. https://doi.org/10.1128/CVI.00547-14