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: Ishrat Sultana, Kevin Yang, Melkamu Getie-Kebtie, Laura Couzens, Lewis Markoff, Michail Alterman, Maryna C Eichelberger
• Journal: Vaccine (Vaccine) Vol. 32 Issue 19 Pg. 2225-30 (Apr 17 2014) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 24613525 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Antibodies, Viral
• Influenza Vaccines
• Vaccines, Inactivated
• Neuraminidase

Topics

• Animals
• Antibodies, Viral (blood)
• Enzyme Stability
• Influenza A Virus, H1N1 Subtype
• Influenza A Virus, H3N2 Subtype
• Influenza B virus
• Influenza Vaccines (chemistry, immunology)
• Mice
• Mice, Inbred BALB C
• Neuraminidase (chemistry, immunology)
• Protein Denaturation
• Temperature
• Vaccine Potency
• Vaccines, Inactivated (chemistry, immunology)