Universal influenza A M2e-HBc vaccine protects against disease even in the presence of pre-existing anti-HBc antibodies.
The extracellular domain of influenza A virus matrix protein 2 (M2e) is strongly conserved. Therefore, vaccines based on M2e can induce broad-spectrum immunity against influenza. We have mainly used recombinant virus-like particles derived from Hepatitis B virus core (HBc) as carrier for efficacious presentation of the M2e antigen. Here, we address whether pre-existing HBc-specific immunity interferes with the protective immune response obtained by M2e-HBc vaccination. Anti-HBc antibodies were induced by immunizing mice with unsubstituted HBc virus-like particles in the presence of two different adjuvants. We demonstrate that pre-existing HBc-specific antibodies affect neither the induction of M2e-specific antibody responses to vaccination with M2e-HBc particles, nor the protective efficacy of the resulting response. These results suggest that vaccination with M2e-HBc can induce protective anti-M2e antibodies even in anti-HBc positive individuals. The implications of these findings are discussed in the context of the clinical development of an M2e-based universal influenza vaccine, which recently successfully completed a Phase I trial.
Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
Marina
M
De Filette
Wouter
W
Martens
Anouk
A
Smet
Michael
M
Schotsaert
Ashley
A
Birkett
Patricia
P
Londoño-Arcila
Walter
W
Fiers
Xavier
X
Saelens
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; D006512:Hepatitis B Core Antigens; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C509609:M2e-HBc influenza vaccine