title: Evaluation of the immunogenicity and protective effects of a trivalent chimeric norovirus P particle immunogen displaying influenza HA2 from subtypes H1, H3 and B.
abstract: The ectodomain of the influenza A virus (IAV) hemagglutinin (HA) stem is highly conserved across strains and has shown promise as a universal influenza vaccine in a mouse model. In this study, potential B-cell epitopes were found through sequence alignment and epitope prediction in a stem fragment, HA2:90-105, which is highly conserved among virus subtypes H1, H3 and B. A norovirus (NoV) P particle platform was used to express the HA2:90-105 sequences from subtypes H1, H3 and B in loops 1, 2 and 3 of the protrusion (P) domain, respectively. Through mouse immunization and microneutralization assays, the immunogenicity and protective efficacy of the chimeric NoV P particle (trivalent HA2-PP) were tested against infection with three subtypes (H1N1, H3N2 and B) of IAV in Madin-Darby canine kidney cells. The protective efficacy of the trivalent HA2-PP was also evaluated preliminarily in vivo by virus challenge in the mouse model. The trivalent HA2-PP immunogen induced significant IgG antibody responses, which could be enhanced by a virus booster vaccination. Moreover, the trivalent HA2-PP immunogen also demonstrated in vitro neutralization of the H3 and B viruses, and in vivo protection against the H3 virus. Our results support the notion that a broadly protective vaccine approach using an HA2-based NoV P particle platform can provide cross-protection against challenge viruses of different IAV subtypes. The efficacy of the immunogen should be further enhanced for practicality, and a better understanding of the protective immune mechanism will be critical for the development of HA2-based multivalent vaccines.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: He
authors.initials: H
authors.lastname: Yin
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Shi
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: He
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Yongjiao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Guan
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Kuai
authors.affiliation: Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Nasteha M
authors.initials: NM
authors.lastname: Haji
authors.affiliation: Norman Bethune Health Science Center, Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Nafisa M
authors.initials: NM
authors.lastname: Haji
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.|Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.|Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, Jilin Province, China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Shan
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D020740:Chimerin Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D056738:Cross Protection; D004285:Dogs; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007114:Immunization; D000071497:Immunogenicity, Vaccine; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology; D009981:Influenza B virus / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D029322:Norovirus / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D020740:Chimerin Proteins; D018985:Epitopes, B-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines