title: Production of H5N1 (NIBRG-14) inactivated whole virus and split virion influenza vaccines and analysis of immunogenicity in mice using different adjuvant formulations.
abstract: Consecutive lots of H5N1 (A/Vietnam/1194/2004 - NIBRG-14) split virion and whole virus vaccines were produced in a pilot-scale laboratory. The average yields of vaccine doses (15 microg HA) per egg were 0.57 doses for H5N1 split virion vaccine and 1.12 for H5N1 whole virus vaccine, compared to 2.09 doses for the seasonal H3N2 split virion vaccine. H5N1 split virion vaccine lots complied with WHO protein content criteria, while some lots of the H5N1 whole virus vaccine showed protein content per dose higher than the limit established. All lots of both vaccines showed ovalbumin (OVA) concentration below the recommended limit. Dose sparing strategies using adjuvant formulations using aluminum hydroxide (Al(OH)(3)) and monophosphoryl lipid A (MPLA) from Bordetella pertussis were tested in mice. Both 3.75 microg HA and 7.5 microg HA of H5N1 split virion vaccine with Al(OH)(3) or Al(OH)(3) plus MPLA in aqueous suspension showed higher hemagglutination-inhibition (HAI) titers when compared to the same vaccine dose without any adjuvant. Immunization with the H5N1 inactivated whole virus vaccine was also performed using 3.75 microg HA and HAI titers were higher than those induced by the split virion vaccine. Moreover, the use of Al(OH)(3) with MPLA as an emulsion induced a further increase in HAI titers.
authors.affiliation: BioIndustrial Division, Instituto/Fundação Butantan, SP, Brazil.
authors.forename: Cosue
authors.initials: C
authors.lastname: Miyaki
authors.forename: Wagner
authors.initials: W
authors.lastname: Quintilio
authors.forename: Eliane N
authors.initials: EN
authors.lastname: Miyaji
authors.forename: Viviane F
authors.initials: VF
authors.lastname: Botosso
authors.forename: Flavia S
authors.initials: FS
authors.lastname: Kubrusly
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Santos
authors.forename: Dmitri
authors.initials: D
authors.lastname: Iourtov
authors.forename: Hisako G
authors.initials: HG
authors.lastname: Higashi
authors.forename: Isaias
authors.initials: I
authors.lastname: Raw
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis; D001886:Bordetella pertussis / Q000737:chemistry; D005260:Female; D006385:Hemagglutination Inhibition Tests; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology*; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000032:analysis; D015164:Vaccines, Inactivated / Q000737:chemistry / Q000276:immunology; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D008050:Lipid A; D015164:Vaccines, Inactivated; D022223:Vaccines, Subunit; D000536:Aluminum Hydroxide; D010047:Ovalbumin; C048436:monophosphoryl lipid A