title: Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge.
abstract: Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15 µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein.
authors.affiliation: Touro University California; Vallejo, CA USA.
authors.forename: Jyothi K
authors.initials: JK
authors.lastname: Mallajosyula
authors.affiliation: Kentucky BioProcessing LLC; Owensboro, KY USA.
authors.forename: Ernie
authors.initials: E
authors.lastname: Hiatt
authors.affiliation: Kentucky BioProcessing LLC; Owensboro, KY USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Hume
authors.affiliation: Kentucky BioProcessing LLC; Owensboro, KY USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Johnson
authors.affiliation: St. Jude Children's Research Hospital; Memphis, TN USA.
authors.forename: Trushar
authors.initials: T
authors.lastname: Jeevan
authors.affiliation: Council for Scientific and Industrial Research; Pretoria, South Africa.
authors.forename: Rachel
authors.initials: R
authors.lastname: Chikwamba
authors.affiliation: Kentucky BioProcessing LLC; Owensboro, KY USA; IC2 Institute; The University of Texas at Austin; Austin, TX USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Pogue
authors.affiliation: Kentucky BioProcessing LLC; Owensboro, KY USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Bratcher
authors.affiliation: Kentucky BioProcessing LLC; Owensboro, KY USA.
authors.forename: Hugh
authors.initials: H
authors.lastname: Haydon
authors.affiliation: St. Jude Children's Research Hospital; Memphis, TN USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: Touro University California; Vallejo, CA USA.
authors.forename: Alison A
authors.initials: AA
authors.lastname: McCormick
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016019:Survival Analysis; D017898:Tobamovirus / Q000737:chemistry; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004337:Drug Carriers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: H1N1; HA subunit protein; Influenza; dose sparing; nanoparticle; plant made pharmaceuticals; vaccination