Properly Folded Bacterially Expressed H1N1 Hemagglutinin Globular Head and Ectodomain Vaccines Protect Ferrets against H1N1 Pandemic Influenza Virus

作者: Surender Khurana , Swati Verma , Nitin Verma , Corey J. Crevar , Donald M. Carter

DOI: 10.1371/JOURNAL.PONE.0011548

关键词: Influenza vaccineNeutralizing antibodyBiologyVaccinationInfluenza A virus subtype H5N1VirusHemagglutinin (influenza)MicrobiologyEctodomainVirologyAntibody

摘要: Background: In the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is most effective approach to prevent large scale mortality morbidity that was associated with 1918 ‘‘Spanish Flu’’. The traditional process in eggs time consuming may not meet demands global required curtail pandemic. Methodology/Principal Findings: Recombinant technology can be used express hemagglutinin (HA) emerging new strain variety systems including mammalian, insect, bacterial cells. this study, two forms HA proteins derived from currently circulating novel H1N1 A/California/07/2009 virus, HA1 (1–330) (1– 480), were expressed purified E. coli under controlled redox refolding conditions favoured proper protein folding. However, only recombinant formed oligomers, functional trimers bound receptor caused agglutination human red blood These vaccinate ferrets prior challenge virus. Both induced neutralizing antibodies, reduced viral loads nasal washes. had higher content multimeric provided better protection fever weight loss at lower dose compared (1–480). Protein yield for ranged around 40 mg/Liter, while (1–480) 0.4–0.8 mg/Liter. Conclusions/Significance: This first study describes system properly folded globular domain trimers, lacking HA2 transmembrane protein, elicit potent antibody responses following protect vivo challenge. combination expression established quality control methods could provide mechanism vaccines pandemic threat.

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