doi:10.1038/s41541-022-00435-7...
Nature
Biomedicine
2022
2/10/2022
The neuraminidase (NA) is an abundant antigen at the surface of influenza virions.
Recent studies have highlighted the immune-protective potential of NA against influenza and defined anti-NA antibodies as an independent correlate of protection.
Even though NA head domain changes at a slightly slower pace than hemagglutinin (HA), NA is still subject to antigenic drift, and therefore an NA-based influenza vaccine antigen may have to be updated regularly and thus repeatedly administered.
NA is a tetrameric type II membrane protein, which readily dissociates into dimers and monomers when expressed in a soluble form.
By using a tetramerizing zipper, such as the tetrabrachion (TB) from Staphylothermus marinus , it is possible to stabilize soluble NA in its active tetrameric conformation, an imperative for the optimal induction of protective NA inhibitory antibodies.
The impact of repetitive immunizations with TB-stabilized antigens on the immunogenicity of soluble TB-stabilized NA is unknown.
We demonstrate that TB is immunogenic in mice.
Interestingly, preexisting anti-TB antibodies enhance the anti-NA antibody response induced by immunization with TB-stabilized NA.
This immune-enhancing effect was transferable by serum and operated independently of activating Fcγ receptors.
We also demonstrate that priming with TB-stabilized NA antigens, enhances the NA inhibitory antibody responses against a heterosubtypic TB-stabilized NA.
These findings have implications for the clinical development of oligomeric vaccine antigens that are stabilized by a heterologous oligomerizing domain.
Catani, João Paulo Portela,Job, Emma R.,Ysenbaert, Tine,Smet, Anouk,Ray, Satyajit,LaRue, Lauren,Stegalkina, Svetlana,Barro, Mario,Vogel, Thorsten U.,Saelens, Xavier, 2022, Pre-existing antibodies directed against a tetramerizing domain enhance the immune response against artificially stabilized soluble tetrameric influenza neuraminidase, Nature