Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus. Issue 38 (11th September 2015)

• Record Type: Journal Article
• Authors: Pushko, Peter; Pujanauski, Lindsey M.; Sun, Xiangjie; Pearce, Melissa; Hidajat, Rachmat; Kort, Thomas; Schwartzman, Louis M.; Tretyakova, Irina; Chunqing, Liu; Taubenberger, Jeffery K.; Tumpey, Terrence M.
• Is Part Of: Vaccine. Volume 33:Issue 38(2015)
• Page Start: 4975
• Page End: 4982
• Publication Date: 2015-09-11
• Subjects: Influenza -- H7N9 -- Influenza vaccine -- Virus-like particles -- VLP; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.07.026
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Recombinant full-length H7 hemagglutinin (rH7) was expressed in Sf9 cells. Purified rH7 forms subviral particles (SVP) of approximately 20 nm in diameter. SVP structures are composed of approximately 3–4 trimers of rH7. Purified rH7 SVP elicit protective immune response in mice and ferrets. Abstract: A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant approaches including hemagglutinin (HA) and virus-like particles (VLPs) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. While high immunogenicity of VLP vaccines has been attributed to the native conformation of HA arranged in the regular repeated patterns within virus-like structures, there is limited data regarding molecular organization of HA within recombinant HA vaccine preparations. In this study, the full-length recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9 cells. We showed that purified full-length rH7 retained functional ability to agglutinate red blood cells and formed oligomeric pleomorphic subviral particles (SVPs) of ∼20 nm in diameter composed of approximately 10 HA0 molecules. No significant quantities of free monomeric HA0 were observed in rH7 preparation by size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs was confirmed in the mouse and ferret challenge models suggesting that SVPs can be used for vaccination against H7N9 virus.