Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens
02/2025
Journal Article
Authors:
El Sahly, H. M.;
Anderson, E. J.;
Jackson, L. A.;
Neuzil, K. M.;
Atmar, R. L.;
Bernstein, D. I.;
Chen, W. H.;
Creech, C. B.;
Frey, S. E.;
Goepfert, P.;
Meier, J.;
Phadke, V.;
Rouphael, N.;
Rupp, R.;
Stapleton, J. T.;
Spearman, P.;
Walter, E. B.;
Winokur, P. L.;
Yildirim, I.;
Williams, T. L.;
Oshinsky, J.;
Coughlan, L.;
Nijhuis, H.;
Pasetti, M. F.;
Krammer, F.;
Stadlbauer, D.;
Nachbagauer, R.;
Tsong, R.;
Wegel, A.;
Roberts, P. C.
Volume:
47
Pagination:
126689
Journal:
Vaccine
URL:
https://www.sciencedirect.com/science/article/pii/S0264410X24013719
DOI:
https://doi.org/10.1016/j.vaccine.2024.126689
Keywords:
Pandemic influenza vaccine hemagglutinin (HA) antigen neuraminidase (NA) antigen NA inhibition (NAI)
Abstract:
Introduction Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans. Material and methods In a series of clinical trials, we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dose priming series had an appreciable effect on NAI antibody responses. Anti-HA stalk antibody responses were minimal and not durable. Conclusions We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness. Clinical Trial Registry Numbers NCT03312231, NCT03318315, NCT03589807, NCT03738241.
