Marlene Fyrstenberg Laursen

• Hinke, Daniëla Maria; Anderson, Ane Marie; Katta, Kirankumar; Laursen, Marlene Fyrstenberg; Tesfaye, Demo Yemane & Werninghaus, Ina Charlotta [Show all 10 contributors for this article] (2024). Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins. Nature Communications. ISSN 2041-1723. 15(1). doi: 10.1038/s41467-024-44889-w.

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• Laursen, Marlene Fyrstenberg; Daniela Maria, Hinke; Bogen, Bjarne & Braathen, Ranveig (2021). An MHC class II-targeted H1-mix Influenza Vaccine Induces Cross-protective Antibody Responses in Mice. Show summary

  Influenza infections are a major cause of morbidity and mortality worldwide. The surface glycoprotein hemagglutinin (HA) is the primary target for neutralizing antibodies, protecting against influenza infections. Within the influenza A virus (IAV) family, HA subtypes H1-H18 exist. In humans, circulating IAVs belonging to H1 and H3 subtypes cause seasonal influenza. Applying influenza vaccines can lower the burden of influenza disease. However, minor genetic mutations causing substitutions of single amino acids in the HA sequence lead to antigenic drift and immune escape of the virus. This lowers the efficacy of current vaccines and annual revaccination is needed. To develop novel influenza vaccines which more broadly protect immunized individuals without the need of an annual boost is consequently of high interest. In our studies, we combined HAs from 4 different H1N1 IAVs into an MHC class II-targeting heterodimeric DNA H1-mix vaccine (H1-mix). Vaccinated mice were followed for several weeks and antibody responses analyzed by ELISA. The H1-mix induced antibodies against a variety of H1s as well as against other subtypes not included in the mix. Furthermore, mice vaccinated with the H1-mix showed complete protection against a heterologous viral infection with the H1N1 virus A/Puerto Rico/8/1934 (PR8), which was not included in the mix. Mice vaccinated with the individual H1s used in the mix vaccine, showed no protection against PR8. This strategy enables an easy adaption of the vaccine to better protect against drifted viral strains, probably by inducing cross-reactive antibodies. This is an important step towards generating a universal influenza vaccine.

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