title: Stability of neuraminidase in inactivated influenza vaccines.
abstract: Influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. Antibodies that block the function of either hemagglutinin (HA) or neuraminidase (NA) contribute to vaccine efficacy, however vaccine potency is based only on HA content. NA protein content in vaccines varies from season to season due to differences in the relative amounts of HA and NA in influenza A, H1N1 and H3N2, and influenza B viruses that are selected for each manufacturing campaign. This, as well as potential inherent differences in NA immunogenicity, may result in varying responses from year to year. Moreover, the antigenic stability of NA is likely to dictate whether similar antibody responses will be obtained to this antigen throughout the shelf-life of the vaccine. To address this factor, we subjected NAs of influenza A (subtypes N1 and N2) and B viruses to denaturing conditions to evaluate the stability of enzyme activity. Each NA type/subtype had unique sensitivity to denaturing conditions. The N2 enzyme activity was more thermostable than that of N1 or influenza B, while the NA activity of influenza B was most resistant to detergent. N1 enzyme activity was most resistant of the three NAs to freeze-thaw cycling. In these experiments, enzyme activity was indicative of the immunogenicity of NA, but was strain-dependent, with greater neuraminidase inhibiting (NI) antibody titers elicited following immunization with the 2009 H1N1 pandemic virus A/California/7/2009, than the previously circulating seasonal H1N1 strain, A/Brisbane/59/2007. Robust NI antibody titers against both N1 and N2 components were induced following vaccination of mice with a trivalent inactivated influenza vaccine. When stored under recommended conditions, the NA of both N1 and N2 subtypes remained immunogenic well after the vaccine expiry date.
authors.affiliation: Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Ishrat
authors.initials: I
authors.lastname: Sultana
authors.affiliation: Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Yang
authors.affiliation: Division of Cellular and Gene Therapies, Office of Cell, Tissue and Gene Therapy, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Melkamu
authors.initials: M
authors.lastname: Getie-Kebtie
authors.affiliation: Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Couzens
authors.affiliation: Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Lewis
authors.initials: L
authors.lastname: Markoff
authors.affiliation: Division of Cellular and Gene Therapies, Office of Cell, Tissue and Gene Therapy, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Michail
authors.initials: M
authors.lastname: Alterman
authors.affiliation: Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA. Electronic address: Maryna.Eichelberger@fda.hhs.gov.
authors.forename: Maryna C
authors.initials: MC
authors.lastname: Eichelberger
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004795:Enzyme Stability; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D009981:Influenza B virus; D007252:Influenza Vaccines / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000737:chemistry* / Q000276:immunology; D011489:Protein Denaturation; D013696:Temperature; D064166:Vaccine Potency; D015164:Vaccines, Inactivated / Q000737:chemistry / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D009439:Neuraminidase
keywords: Immunogenicity; Influenza; Neuraminidase; Stability; Vaccines