Targeting vaccine fusion proteins to APCs increases immunogenicity of adenoviral and mRNA-LNP vaccines

  • Mol Ther. 2026 Jun 26:S1525-0016(26)00511-3. doi: 10.1016/j.ymthe.2026.06.034.
Marlene Fyrstenberg Laursen  1 ,  Francis Combes  2 ,  Arnar Gudjonsson  1 ,  Louise Bjerkan  1 ,  Jérémie Parot  2 ,  Demo Yemane Tesfaye  1 ,  Frida J Pettersson  2 ,  Alicja Molska  2 ,  Ganesh Ram R Visweswaran  1 ,  Geneviève M Labbé  3 ,  Simon J Draper  3 ,  Sven Even Borgos  2 ,  Bjarne Bogen  1 ,  Ranveig Braathen  4
Affiliations
  • 1. Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
  • 2. Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
  • 3. Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
  • 4. Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: [email protected].
PMID: 42363600 DOI: 10.1016/j.ymthe.2026.06.034
Abstract

mRNA-lipid nanoparticle (LNP) and adenoviral delivery of vaccines have proven effective during the COVID-19 pandemic. Herein, we explored whether antigen-presenting cell (APC)-targeting of antigens could further enhance immunogenicity of these delivery formats. Experiments were performed in mouse models for malaria (Plasmodium falciparum reticulocytes-binding protein homolog 5, PfRH5, antigen) and influenza (hemagglutinin, HA, antigen). We used genetic constructs encoding bivalent fusion proteins that target antigens to MHC class II (MHCII) molecules on professional APCs. We demonstrate that MHCII-targeted fusion proteins bound to professional APCs and that such APC-targeting increased antibody and T cell responses as well as protection against Influenza Virus. The results suggest that the injected mRNA-LNP and adenoviral vectors resulted in secretion of fusion proteins that targeted APCs. Employing the APC-targeting principle could enhance efficiency of adenoviral and mRNA-LNP vaccines against a variety of diseases.

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