title: Protective immunity afforded by inactivated H5N1 (NIBRG-14) vaccine requires antibodies against both hemagglutinin and neuraminidase in mice.
abstract: BACKGROUND
  Hemagglutination-inhibition (HI) antibody titers correlate with protective immunity to seasonal influenza viruses. However, inactivated H5N1 influenza vaccines from Vietnam 2004 strains afford protection without producing high or even detectable HI antibodies.
  
  
  METHODS
  BALB/c mice were immunized twice (at a 3-week interval) with inactivated whole-virus influenza vaccine produced using reverse genetics, with the internal genes of A/PR/8/34 (a high-yield strain) and the hemagglutinin (HA) and neuraminidase (NA) genes of A/Vietnam/1194/04 (H5N1) virus (NIBRG-14) adjuvanted with alum (5 microg of HA). Either HA- or NA-binding antibodies were absorbed from the immune serum. The protective efficacy of these antibodies was determined by injecting the absorbed serum into severe combined immunodeficiency mice, which were then challenged with highly pathogenic H5N1 virus (A/Vietnam/Jp1203/2004; Japanese isolate of A/Vietnam/1203/2004).
  
  
  RESULTS
  The NIBRG-14 vaccine elicited levels of anti-HA antibodies similar to levels elicited by the H1N1 vaccines, as well as levels of anti-NA antibodies higher than those elicited by the H1N1 vaccines. The absorption of either anti-HA or anti-NA antibody from immune serum samples obtained from NIBRG-14-vaccinated mice significantly reduced the protective efficacy of the serum.
  
  
  CONCLUSIONS
  For NIBRG-14 vaccines to confer protection to vaccinated hosts, both anti-HA and anti-NA antibodies are required. This finding implies that the measurement of both antibody levels may be required for accurate evaluation of vaccine efficacy.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan. ytakahas@nih.go.jp
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hara
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.forename: Ai
authors.initials: A
authors.lastname: Ninomiya
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Takagi
authors.forename: Takato
authors.initials: T
authors.lastname: Odagiri
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D005434:Flow Cytometry; D006387:Hemagglutination, Viral / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000627:therapeutic use*
chemical_list: D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D009439:Neuraminidase