title: A VLP vaccine induces broad-spectrum cross-protective antibody immunity against H5N1 and H1N1 subtypes of influenza A virus.
abstract: The recent threats of influenza epidemics and pandemics have prioritized the development of a universal vaccine that offers protection against a wider variety of influenza infections. Here, we demonstrate a genetically modified virus-like particle (VLP) vaccine, referred to as H5M2eN1-VLP, that increased the antigenic content of NA and induced rapid recall of antibody against HA(2) after viral infection. As a result, H5M2eN1-VLP vaccination elicited a broad humoral immune response against multiple viral proteins and caused significant protection against homologous RG-14 (H5N1) and heterologous A/California/07/2009 H1N1 (CA/07) and A/PR/8/34 H1N1 (PR8) viral lethal challenges. Moreover, the N1-VLP (lacking HA) induced production of a strong NA antibody that also conferred significant cross protection against H5N1 and heterologous CA/07 but not PR8, suggesting the protection against N1-serotyped viruses can be extended from avian-origin to CA/07 strain isolated in humans, but not to evolutionally distant strains of human-derived. By comparative vaccine study of an HA-based VLP (H5N1-VLP) and NA-based VLPs, we found that H5N1-VLP vaccination induced specific and strong protective antibodies against the HA(1) subunit of H5, thus restricting the breadth of cross-protection. In summary, we present a feasible example of direction of VLP vaccine immunity toward NA and HA(2), which resulted in cross protection against both seasonal and pandemic influenza strains, that could form the basis for future design of a better universal vaccine.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Wu
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Yeh
authors.forename: Jia-Tsrong
authors.initials: JT
authors.lastname: Chan
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Yang
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Yang
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Liu
authors.forename: Ho-Sheng
authors.initials: HS
authors.lastname: Wu
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002645:Chickens; D056738:Cross Protection / Q000276:immunology*; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle; D009439:Neuraminidase