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Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages.

ABSTRACT: A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxicity and cell-mediated immune responses. Complete protection of the animals required the entire codon-optimized HA2 sequence that elicited a balanced immune response, whereas truncated vaccines without either the fusion peptide or the transmembrane domain reduced the efficacy of protection. Finally, the vaccines did not demonstrate any sign of disease exacerbation following lung pathology and morbidity monitoring. Collectively, these data suggest that it could be worth further exploring this prototype universal vaccine because of its considerable efficacy, safety, and breadth of protection.

SUBMITTER: Gravel C

PROVIDER: S-EPMC8586812 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages.

Gravel Caroline C Muralidharan Abenaya A Duran Amparo A Zetner Adrian A Pfeifle Annabelle A Zhang Wanyue W Hashem Anwar A Tamming Levi L Farnsworth Aaron A Loemba Hugues H Chen Wangxue W Krammer Florian F Safronetz David D Cao Jingxin J Wang Lisheng L Sauve Simon S Rosu-Myles Michael M Van Domselaar Gary G Li Xuguang X

iScience 20211021 11

A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxici ...[more]

PMID: 34805790

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Project description:Dabie Bandavirus (DBV), previously known as Severe Fever with Thrombocytopenia Syndrome (SFTS) Virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ∼50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. Accordingly, our immune-competent ferret model demonstrates an age (>4 years old)-dependent DBV infection and pathogenesis that fully recapitulates human clinical manifestation. To protect the aged population from DBV-induced SFTS, vaccine should carry robust immunogenicity with high safety profile. Previous studies have shown that glycoproteins Gn/Gc are the most effective antigens to induce both neutralizing antibody (NAb)-and T cell-mediated immunity for full protection from DBV infection. Here, we report the development of a protein subunit vaccine with 24-mer self-assembling ferritin (FT) nanoparticle to present the DBV Gn head region (GnH) to enhance immunogenicity. Anion exchange chromatography and size exclusion chromatography readily purified the GnH-FT nanoparticles to homogeneity with structural integrity. Mice immunized with GnH-FT nanoparticles induced robust NAb response and T-cell immunity against DBV Gn. Furthermore, aged ferrets immunized with GnH-FT nanoparticles were fully protected from DBV challenge without SFTS symptoms such as body weight loss, thrombocytopenia, leukopenia, and fatality. This study demonstrates that DBV GnH-FT nanoparticles provide an efficient vaccine efficacy in mouse and aged ferret models and should be an outstanding vaccine candidate targeted for the aged population against fatal DBV infection.ImportanceDabie Bandavirus (DBV) is an emerging tick-borne virus that causes Severe Fever with Thrombocytopenia Syndrome (SFTS) in infected patients. Human SFTS symptoms progress from fever, fatigue, and muscle pain to the depletion of white blood cells and platelets with fatality rates up to 30%. The recent spread of its vector tick to over 20 states in the United States increases the potential for outbreaks of the SFTS beyond the East Asia. Thus, the development of vaccine to control this rapidly emerging virus is a high priority.In this study, we applied self-assembling ferritin (FT) nanoparticle to enhance the immunogenicity of DBV Gn head domain (GnH) as a vaccine target. Mice immunized with the GnH-FT nanoparticle vaccine induced potent antibody responses and cellular immunity. Immunized aged ferrets were fully protected from the lethal challenge of DBV. Our study describes the GnH-FT nanoparticle vaccine candidate that provides protective immunity against the emerging DBV infection.

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Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages.

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Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages.

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