Influenza-pseudotyped Gag virus-like particle vaccines provide broad protection against highly pathogenic avian influenza challenge

Abstract Influenza-pseudotyped Gag virus-like particles (VLPs) were produced via the expression of influenza hemagglutinin (HA), neuraminidase (NA) and the murine leukemia virus Gag product in the baculovirus-insect cell expression system. Hemagglutination specific activities of sucrose gradient-pur...

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Bibliographic Details
Published in:Vaccine 2009-01, Vol.27 (4), p.530-541
Main Authors: Haynes, Joel R, Dokken, Leslie, Wiley, James A, Cawthon, Andrew G, Bigger, John, Harmsen, Allen G, Richardson, Charles
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Antigens
Applied microbiology
Avian flu
Baculoviridae - immunology
Baculovirus
Biological and medical sciences
Cells, Cultured
Cloning
Female
Ferrets - immunology
Fundamental and applied biological sciences. Psychology
Gene Products, gag - administration & dosage
Gene Products, gag - immunology
Genes
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Hemagglutinin Glycoproteins, Influenza Virus - isolation & purification
Influenza
Influenza A Virus, H1N1 Subtype - immunology
Influenza A Virus, H5N1 Subtype - immunology
Influenza Vaccines - immunology
Male
Mice
Mice, Inbred BALB C
Microbiology
Miscellaneous
Murine leukemia virus
Mustela
Neuraminidase - immunology
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - prevention & control
Pandemics
Proteins
Time Factors
Vaccine
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Virion - immunology
Virology
Virus-like particles
Viruses
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Summary:Abstract Influenza-pseudotyped Gag virus-like particles (VLPs) were produced via the expression of influenza hemagglutinin (HA), neuraminidase (NA) and the murine leukemia virus Gag product in the baculovirus-insect cell expression system. Hemagglutination specific activities of sucrose gradient-purified VLPs were similar to those of egg-grown influenza viruses but particle morphologies were gamma retrovirus-like in the form of consistent 100 nm spheres. Immunization of mice and ferrets demonstrated robust immunogenicity and protection from challenge with no measurable morbidity. Ferret data were striking in that immunization with H5N1 VLPs representing either A/Vietnam/1203/04 or A/Indonesia/5/05 resulted in solid protection against highly pathogenic A/Vietnam/1203/04 challenge with no detectable virus in the upper respiratory tract post-challenge in either group. H1N1 VLP immunization of ferrets resulted in partial protection against H5N1 challenge with markedly accelerated virus clearance from the upper respiratory tract relative to controls. The immunogenicity of influenza-pseudotyped VLPs was not dependent on the adjuvant properties of replication competent contaminating baculovirus. These data demonstrate robust vaccine protection of Gag-based, influenza-pseudotyped VLPs carrying a variety of influenza antigens and suggest applicability toward a number of additional respiratory viruses.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2008.11.011