title: Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine.
abstract: The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6-14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine.
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2.
authors.forename: Damien
authors.initials: D
authors.lastname: Carignan
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2.
authors.forename: Ariane
authors.initials: A
authors.lastname: Thérien
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2.
authors.forename: Gervais
authors.initials: G
authors.lastname: Rioux
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Paquet
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2.
authors.forename: Marie-Ève Laliberté
authors.initials: ML
authors.lastname: Gagné
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2.
authors.forename: Marilène
authors.initials: M
authors.lastname: Bolduc
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2.
authors.forename: Pierre
authors.initials: P
authors.lastname: Savard
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Infectious Disease Research Center, Laval University, 2705 boul. Laurier, Quebec City, PQ, Canada G1V 4G2. Electronic address: denis.Leclerc@crchudequebec.ulaval.ca.
authors.forename: Denis
authors.initials: D
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004337:Drug Carriers; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000517:prevention & control; D017863:Potexvirus / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D004337:Drug Carriers; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Influenza; M2e; Matrix protein 2; Nanoparticles; PapMV; Vaccine