title: A cationic liposome-DNA complexes adjuvant (JVRS-100) enhances the immunogenicity and cross-protective efficacy of pre-pandemic influenza A (H5N1) vaccine in ferrets.
abstract: Influenza A (H5N1) viruses continue to pose a public health threat. As inactivated H5N1 vaccines are poorly immunogenic, adjuvants are needed to improve the immunogenicity of H5N1 vaccine in humans. Here, we investigated the immunogenicity and cross-protective efficacy in ferrets of a clade 2.2-derived vaccine with addition of JVRS-100, an adjuvant consisting of cationic liposome-DNA complexes (CLDC). After the first vaccination, significantly higher levels of hemagglutination-inhibition (HAI) and neutralizing antibody titers were detected in ferrets immunized with adjuvanted vaccine compared to unadjuvanted vaccine. Following a second dose of adjuvanted vaccine, HAI antibody titers of ≥ 40 were detected against viruses from multiple H5N1 clades. HAI antibodies against newly isolated H5N2 and H5N8 viruses were also augmented by JVRS-100. Ferrets were challenged with a heterologous H5N1 virus. All ferrets that received two doses of adjuvanted vaccine exhibited mild illness, significantly reduced nasal wash virus titers and protection from lethal challenge. In contrast, ferrets that received unadjuvanted vaccine showed greater weight loss, high viral titers and 3 of 6 animals succumbed to the lethal challenge. Our results indicate that the addition of JVRS-100 to H5N1 vaccine enhanced immunogenicity and cross-protection against lethal H5N1 virus disease in ferrets. JVRS-100 warrants further investigation as a potential adjuvant for influenza vaccines.
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Xiangjie
authors.initials: X
authors.lastname: Sun
authors.affiliation: Juvaris BioTherapeutics, Pleasanton, CA 94566, USA.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Fairman
authors.affiliation: Department of Pediatrics, Interdepartmental Program in Immunology, and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Levine
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: xal0@cdc.gov.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Lu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis*; D002412:Cations; D056738:Cross Protection; D004247:DNA / Q000737:chemistry / Q000276:immunology*; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology / Q000494:pharmacology*; D008081:Liposomes / Q000737:chemistry / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D015164:Vaccines, Inactivated
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D002412:Cations; D007252:Influenza Vaccines; D008081:Liposomes; D015164:Vaccines, Inactivated; D004247:DNA
keywords: Antibody response; CLDC adjuvant; Cross-protection; Ferrets; Influenza A (H5N1) vaccine