title: Intranasal vaccination with a plant-derived H5 HA vaccine protects mice and ferrets against highly pathogenic avian influenza virus challenge.
abstract: Highly pathogenic avian influenza H5N1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. Mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. In this study, we assessed the protective efficacy of hemagglutinin (HA) from the A/Indonesia/05/05 (H5N1) strain of influenza virus that was produced by transient expression in plants. The plant-derived vaccine, in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP) was used for intranasal immunization of mice and ferrets, before challenge with a lethal dose of the A/Indonesia/05/05 (H5N1) virus. Mice vaccinated with 15 μg or 5 μg of adjuvanted HA survived the viral challenge, while all control mice died within 10 d of challenge. Vaccinated animals elicited serum hemagglutination inhibition, IgG and IgA antibody titers. In the ferret challenge study, all animals vaccinated with the adjuvanted plant vaccine survived the lethal viral challenge, while 50% of the control animals died. In both the mouse and ferret models, the vaccinated animals were better protected from weight loss and body temperature changes associated with H5N1 infection compared with the non-vaccinated controls. Furthermore, the systemic spread of the virus was lower in the vaccinated animals compared with the controls. Results presented here suggest that the plant-produced HA-based influenza vaccine adjuvanted with c-di-GMP is a promising vaccine/adjuvant combination for the development of new mucosal influenza vaccines.
authors.affiliation: a National Institute for Biological Standards and Control; Medicines and Healthcare Products Regulatory Agency ; Potters Bar , UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Major
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Rishi D
authors.initials: RD
authors.lastname: Pathirana
authors.forename: Kate
authors.initials: K
authors.lastname: Guilfoyle
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shoji
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cox
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D008297:Male; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D030821:Plants, Genetically Modified; D016019:Survival Analysis; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000276:Adjuvants, Immunologic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; C109963:hemagglutinin, avian influenza A virus; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP
keywords: (3′; 5′)-cyclic dimeric guanylic acid; adjuvant; c-di-GMP; ferret infection model; influenza H5N1; intranasal vaccination; mice, plant vaccine