Improvement of the PapMV nanoparticle adjuvant property through an increased of its avidity for the antigen [influenza NP].
The principal caveat of existing influenza vaccine is their failure to provide long-term protection. This lack of efficiency is caused by persistent (drift) and dramatic (shift) antigenic changes on the major surface proteins, the main target of protective immunity generated by traditional vaccines. Alternatively, vaccination with most conserved protein, like the nucleoprotein (NP) can stimulate immunity against multiple serotypes and could potentially provides an extended protection. The NP antigen contains more than 90% protein sequence homology among influenza A isolates and it also contains dominant CTL targets epitopes that made this antigen an attractive target for developing universal vaccine. However, NP protein is a weak antigen and need the use of adjuvant to increase its immunogenicity. We have developed an innovative high avidity VLP (HAV) nanoparticle to improve its adjuvant property to the NP antigen. The nanoparticles are derived from papaya mosaic virus capsid protein (PapMV CP) produced in a bacteria expression system. We generated the HAV by adding an affinity peptide directed to the NP protein at the surface of the VLPs. The fusions of the affinity peptide to PapMV VLPs increased the avidity of PapMV VLPs to NP protein. This modification enhanced the humoral and the IFN-γ response directed to NP. Moreover, the immunity generated by the HAV adjuvanted NP vaccine improved the protection of vaccinated mice to a challenge with influenza virus. The protection was characterized by accelerated virus elimination after the onset of infection and rapid recovery of the vaccinated animals.
Infectious Disease Research Centre, CHUL, Laval University, 2705 boul. Laurier, Quebec city, PQ, G1V 4G2, Canada.
Christian
C
Savard
Marie-Ève
MÈ
Laliberté-Gagné
Cindy
C
Babin
Marilène
M
Bolduc
Annie
A
Guérin
Karine
K
Drouin
Marie-Andrée
MA
Forget
Nathalie
N
Majeau
Réjean
R
Lapointe
Denis
D
Leclerc
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D056724:Immunity, Humoral; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D017863:Potexvirus / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D036022:Capsid Proteins; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins