tetano
Editor, Senior Moderator
Mol Ther
. 2023 Mar 16;S1525-0016(23)00133-8.
doi: 10.1016/j.ymthe.2023.03.012. Online ahead of print.
Neuraminidase delivered as an APC-targeted DNA vaccine induces protective antibodies against influenza
Ina Charlotta Werninghaus[SUP] 1 [/SUP], Daniëla Maria Hinke[SUP] 2 [/SUP], Even Fossum[SUP] 2 [/SUP], Bjarne Bogen[SUP] 3 [/SUP], Ranveig Braathen[SUP] 1 [/SUP]
Affiliations
Abstract
Conventional influenza vaccines focus on hemagglutinin (HA). However, antibody responses to neuraminidase (NA) have been established as an independent correlate of protection. Here, we introduced the ectodomain of NA into DNA vaccines that as translated dimeric vaccine proteins target antigen-presenting cells (APCs). The targeting was mediated by a scFv specific for MHC class II which is genetically linked to NA via a dimerization motif. A single immunization of BALB/c mice elicited strong and long-lasting NA-specific antibodies that inhibited NA enzymatic activity and reduced viral replication. Vaccine-induced NA immunity completely protected against a homologous influenza virus and out-competed NA immunity induced by a conventional inactivated virus vaccine. The protection was mainly mediated by antibodies, although NA-specific T cells also contributed. Both APC-targeting and antigen bivalency were crucial for vaccine efficacy. The APC-targeted vaccine was potent at low doses of DNA, indicating a dose-sparing effect. Similar results were obtained with NA vaccines that targeted different surface molecules on dendritic cells. Interestingly, the protective efficacy of NA as antigen compared favorably with HA and therefore ought to receive more attention in influenza vaccine research.
. 2023 Mar 16;S1525-0016(23)00133-8.
doi: 10.1016/j.ymthe.2023.03.012. Online ahead of print.
Neuraminidase delivered as an APC-targeted DNA vaccine induces protective antibodies against influenza
Ina Charlotta Werninghaus[SUP] 1 [/SUP], Daniëla Maria Hinke[SUP] 2 [/SUP], Even Fossum[SUP] 2 [/SUP], Bjarne Bogen[SUP] 3 [/SUP], Ranveig Braathen[SUP] 1 [/SUP]
Affiliations
- PMID: 36926694
- DOI: 10.1016/j.ymthe.2023.03.012
Abstract
Conventional influenza vaccines focus on hemagglutinin (HA). However, antibody responses to neuraminidase (NA) have been established as an independent correlate of protection. Here, we introduced the ectodomain of NA into DNA vaccines that as translated dimeric vaccine proteins target antigen-presenting cells (APCs). The targeting was mediated by a scFv specific for MHC class II which is genetically linked to NA via a dimerization motif. A single immunization of BALB/c mice elicited strong and long-lasting NA-specific antibodies that inhibited NA enzymatic activity and reduced viral replication. Vaccine-induced NA immunity completely protected against a homologous influenza virus and out-competed NA immunity induced by a conventional inactivated virus vaccine. The protection was mainly mediated by antibodies, although NA-specific T cells also contributed. Both APC-targeting and antigen bivalency were crucial for vaccine efficacy. The APC-targeted vaccine was potent at low doses of DNA, indicating a dose-sparing effect. Similar results were obtained with NA vaccines that targeted different surface molecules on dendritic cells. Interestingly, the protective efficacy of NA as antigen compared favorably with HA and therefore ought to receive more attention in influenza vaccine research.