Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform.
With the emergence of highly virulent influenza viruses and the consequent risk of pandemics, new approaches to designing universal influenza vaccines are urgently needed. In this report, we demonstrate the potential of using a papaya mosaic virus (PapMV) platform carrying the universal M2e influenza epitope (PapMV-CP-M2e) as a candidate flu vaccine. We show that PapMV-CP-M2e virus-like particles (VLPs) can induce production in mice of anti-M2e antibodies that can recognize influenza-infected cells. PapMV-CP-M2e discs made of 20 coat protein (CP) subunits were shown to be poorly immunogenic compared to PapMV-CP-M2e VLPs composed of several hundred CP subunits. We also show that addition of either alum or PapMV-CP VLPs as adjuvant dramatically increased the immunogenicity of PapMV-CP-M2e-containing vaccine, and led to 100% protection against a challenge of 4LD(50) with the WSN/33 strain. These results show, for the first time, the potential of a recombinant plant virus protein to serve as both peptide delivery system and adjuvant in the crucial field of influenza vaccine development.
Denis
Jérôme
J
Centre de Recherche en Infectiologie, Pavillon CHUL, Université Laval, 2705 boulevard Laurier, Québec, PQ, G1V 4G2 Canada.
Acosta-Ramirez
Elizabeth
E
Zhao
Yinghi
Y
Hamelin
Marie-Eve
ME
Koukavica
Irena
I
Baz
Mariana
M
Abed
Yacine
Y
Savard
Christian
C
Pare
Christine
C
Lopez Macias
Constantino
C
Boivin
Guy
G
Leclerc
Denis
D
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral; D005822:Genetic Vectors; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D017863:Potexvirus / Q000235:genetics*; D016019:Survival Analysis; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D022701:Virosomes / Q000008:administration & dosage / Q000494:pharmacology; D000086082:Viroporin Proteins
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins; D022701:Virosomes; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C041524:aluminum sulfate