title: Immunologic characterization of a rhesus macaque H1N1 challenge model for candidate influenza virus vaccine assessment.
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.
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Skinner
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Zurawski
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Chie
authors.initials: C
authors.lastname: Sugimoto
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Vinet-Oliphant
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Vinod
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Kasi
authors.initials: K
authors.lastname: Russell-Lodrigue
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Oncovir, Inc., Washington, DC, USA.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Salazar
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kuroda
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA gerardz@baylorhealth.edu.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D006801:Humans; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008253:Macaca mulatta; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines