title: Squalene-adjuvanted H7N9 virus vaccine induces robust humoral immune response against H7N9 and H7N7 viruses.
abstract: Recent cases of avian influenza H7N9 have caused great concerns that virus may become transmittable between humans. It is imperative to develop an effective vaccine to fight against the pandemic potential of this H7N9 influenza virus to protect human from the disease. This study aims to investigate an optimized formulation for the development of H7N9 vaccines. Various doses of H7N9 inactivated whole or split-virus antigens (0.5, 1.5, or 3 μg based on hemagglutinin content) combined with squalene-based adjuvant (AddaVAX), aluminum hydroxide Al(OH)3 or without adjuvant were evaluated for the efficacy of H7N9 vaccine regiments in mice. With either H7N9 whole or split-virus based vaccines, AddaVAX-adjuvanted formulations were the most immunogenic in eliciting significant humoral immune response against H7N9 virus and exhibited strong cross-reactive response in hemagglutination inhibition (HAI) and viral-neutralization assays against H7N7 virus as well. In contrast, formulations with Al(OH)3 or without adjuvant were less immunogenic and elicited lower titers of HAI and microneutralization assays against both viruses. Dose-sparing experiments suggested that the formulation with as low as 0.004 μg of split or whole virus vaccine antigens together with 50% AddaVAX provided sufficient sero-protective HAI titers and achieved essential virus-neutralizing antibody titers against H7-subtype influenza viruses in mice. Protection experiments demonstrated that the formulation of 0.004 μg to 0.5 μg of split-virion vaccines with AddaVAX conferred full protection against viral challenge up to 100 LD50 of wild-type H7N9 virus, with 0% survival in placebo group. Taken together, our study demonstrates that squalene-based adjuvant can significantly enhance the protective efficacy of H7N9 virus vaccine and provides a useful strategy to confront the potential pandemic outbreaks of H7N9 virus.
authors: Adimmune Corporation, Taichung, Taiwan.
authors: Chia-Ying
authors: CY
authors: Wu
authors: Adimmune Corporation, Taichung, Taiwan.
authors: Ching-Yuan
authors: CY
authors: Chang
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Hsiu-Hua
authors: HH
authors: Ma
authors: Adimmune Corporation, Taichung, Taiwan.
authors: Chiung-Wen
authors: CW
authors: Wang
authors: Adimmune Corporation, Taichung, Taiwan.
authors: Yung-Tsung
authors: YT
authors: Chen
authors: Agricultural Biotech Research Center, Academia Sinica, Taipei, Taiwan.
authors: Pei-Wen
authors: PW
authors: Hsiao
authors: Adimmune Corporation, Taichung, Taiwan.
authors: Ching-Chuan
authors: CC
authors: Chang
authors: Adimmune Corporation, Taichung, Taiwan.
authors: Chi-Hsien
authors: CH
authors: Chan
authors: Adimmune Corporation, Taichung, Taiwan.
authors: Chung-Cheng
authors: CC
authors: Liu
authors: Adimmune Corporation, Taichung, Taiwan. Electronic address: JR_Chen@adimmune.com.tw.
authors: Juine-Ruey
authors: JR
authors: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D003429:Cross Reactions; D005260:Female; D006385:Hemagglutination Inhibition Tests; D056724:Immunity, Humoral; D053126:Influenza A Virus, H7N7 Subtype / Q000276:immunology*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011136:Polysorbates / Q000008:administration & dosage*; D013185:Squalene / Q000008:administration & dosage*; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: C000590912:Addavax; D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D011136:Polysorbates; D015164:Vaccines, Inactivated; D022223:Vaccines, Subunit; D000536:Aluminum Hydroxide; D013185:Squalene
keywords: Adjuvant; H7N7; H7N9; Humoral immune response; Inactivated virus vaccine; Pandemic influenza