Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice.
Highly pathogenic H5N1 influenza shares the same neuraminidase (NA) subtype with the 2009 pandemic (H1N1pdm09), and cross-reactive NA immunity might protect against or mitigate lethal H5N1 infection. In this study, mice were either infected with a sublethal dose of H1N1pdm09 or were vaccinated and boosted with virus-like particles (VLP) consisting of the NA and matrix proteins, standardized by NA activity and administered intranasally, and were then challenged with a lethal dose of HPAI H5N1 virus. Mice previously infected with H1N1pdm09 survived H5N1 challenge with no detectable virus or respiratory tract pathology on day 4. Mice immunized with H5N1 or H1N1pdm09 NA VLPs were also fully protected from death, with a 100-fold and 10-fold reduction in infectious virus, respectively, and reduced pathology in the lungs. Human influenza vaccines that elicit not only HA, but also NA immunity may provide enhanced protection against the emergence of seasonal and pandemic viruses.
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3203, USA.
Judith D
JD
Easterbrook
Louis M
LM
Schwartzman
Jin
J
Gao
John C
JC
Kash
David M
DM
Morens
Laura
L
Couzens
Hongquan
H
Wan
Maryna C
MC
Eichelberger
Jeffery K
JK
Taubenberger
D000818:Animals; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology*; D009976:Orthomyxoviridae Infections; D016019:Survival Analysis; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000276:immunology
D007252:Influenza Vaccines; D022721:Vaccines, Virosome; D009439:Neuraminidase