Influenza M1 VLPs containing neuraminidase induce heterosubtypic cross-protection.
Influenza virus like particles (VLPs) containing hemagglutinin were previously demonstrated to induce protection against the homologous strains. However, little information is available on the protective role of neuraminidase (NA), the second major glycoprotein. In this study, we developed VLPs (NA VLPs) containing NA and M1 derived from A/PR/8/34 (H1N1) influenza virus, and investigated their ability to induce protective immunity. Intranasal immunization with NA VLPs induced serum antibody responses to H1N1 and H3N2 influenza A viruses as well as significant neuraminidase inhibition activity. Importantly, mice immunized with NA VLPs were 100% protected against lethal infection by the homologous A/PR/8/34 (H1N1) as well as heterosubtypic A/Philippines/82 (H3N2) virus, although body weight loss was observed after lethal challenge with heterosubtypic H3N2 virus. The present study therefore provides evidence that influenza VLPs containing M1 and NA are capable of inducing immunity to homologous as well as antigenically distinct influenza A virus strains.
Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul 130-701, Korea.
Fu-Shi
FS
Quan
Min-Chul
MC
Kim
Byeong-Jae
BJ
Lee
Jae-Min
JM
Song
Richard W
RW
Compans
Sang-Moo
SM
Kang
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002642:Chick Embryo; D056738:Cross Protection; D007106:Immune Sera / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D007106:Immune Sera; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; D058425:Vaccines, Virus-Like Particle; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase