The effect of calcium and magnesium on activity, immunogenicity, and efficacy of a recombinant N1/N2 neuraminidase vaccine
Luca T. Giurgea,
Jae-Keun Park,
Kathie-Anne Walters,
Kelsey Scherler,
Adriana Cervantes-Medina,
Ashley Freeman,
Luz Angela Rosas,
John C. Kash,
Jeffery K. Taubenberger,
Matthew J. Memoli
Affiliations
Luca T. Giurgea
LID Clinical Studies Unit, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Jae-Keun Park
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kathie-Anne Walters
Institute for Systems Biology
Kelsey Scherler
Institute for Systems Biology
Adriana Cervantes-Medina
LID Clinical Studies Unit, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ashley Freeman
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Luz Angela Rosas
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
John C. Kash
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Jeffery K. Taubenberger
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Matthew J. Memoli
LID Clinical Studies Unit, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Abstract Despite the importance of immunity against neuraminidase (NA), NA content and immunogenicity are neglected in current influenza vaccines. To address this, a recombinant N1/N2 NA vaccine (NAV) was developed. Stability assays were used to determine optimal temperature and buffer conditions for vaccine storage. The effect of divalent cation-related enhancement of NA stability and activity on N1 and N2 immunogenicity and efficacy against viral challenge was assessed. Differences in activity between N1 and N2 and cation-related activity enhancement did not translate into differences in immunogenicity or efficacy. NAV-vaccinated mice showed robust antibody titers against N1 and N2, and after challenge with influenza A (H1N1) virus, decreased viral titers and decreased antiviral and inflammatory responses by transcriptomic analysis. These findings provide guidance for optimal storage and assessment of NA-based vaccines and confirm the importance of NA in influenza vaccination strategies in attenuating viral replication and limiting inflammatory responses necessary to clear infection.
