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

Marlene Fyrstenberg Laursen; Francis Combes; Arnar Gudjonsson; Louise Bjerkan; Jérémie Parot; Demo Yemane Tesfaye; Frida J Pettersson; Alicja Molska; Ganesh Ram R Visweswaran; Geneviève M Labbé; Simon J Draper; Sven Even Borgos; Bjarne Bogen; Ranveig Braathen

doi:10.1016/j.ymthe.2026.06.034

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. Online ahead of print.

Authors

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, UK.
⁴ Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: ranveig.braathen@medisin.uio.no.

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 the immunogenicity of these delivery formats. Experiments were performed in mouse models for malaria (Plasmodium falciparum reticulocyte-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 the influenza virus. The results suggest that the injected mRNA-LNP and adenoviral vectors resulted in the secretion of fusion proteins that targeted APCs. Employing the APC-targeting principle could enhance the efficiency of adenoviral and mRNA-LNP vaccines against a variety of diseases.

Keywords: APC targeting; AdHu5; LNP; influenza; mRNA; malaria; vaccines; viral vector.