Photochemical internalization enhances in vivo immunity to peptide‑ and protein‑based vaccines with synthetic dsRNA adjuvantsDownload PDF Download PDF ArticleOpen accessPublished: 09 August 2026Pål Kristian Selbo ORCID: orcid.org/0000-0002-5310-057X1,Arno Bruel ORCID: orcid.org/0009-0003-2644-80731,2,Monika Håkerud ORCID: orcid.org/0009-0002-1227-99371,Anne Grete Nedberg ORCID: orcid.org/0009-0004-8866-56601,Victoria Tudor Edwards ORCID: orcid.org/0009-0000-9471-30841,2,Gustav Gaudernack ORCID: orcid.org/0000-0002-9678-74473,Pål Johansen ORCID: orcid.org/0000-0002-5055-62994,Kristian Berg ORCID: orcid.org/0000-0002-7816-75431 &…Anders Høgset ORCID: orcid.org/0000-0002-2562-99512 npj Vaccines (2026) Cite this articleSave articleView saved research We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.AbstractEfficient priming of antigen‑specific CD8⁺ T cells remains a major challenge for peptide‑ and protein‑based therapeutic vaccines targeting cancer and intracellular pathogens, despite the use of potent innate immune adjuvants such as synthetic double‑stranded RNA (dsRNA). In this study, we evaluated photochemical internalization (PCI), an endosomal escape technology, as a strategy to enhance vaccine‑induced immunity in combination with the dsRNA adjuvants poly(I:C) and poly‑ICLC. In mouse models, PCI combined with the SIINFEKL peptide and poly(I:C) increased circulating antigen‑specific CD8⁺ T cells by approximately 100‑fold compared with vaccination without PCI. Using a synthetic long HPV16 E7 peptide, PCI with poly(I:C) induced robust effector- and memory-phenotype CD8⁺ T‑cell responses and strong anti‑tumour activity in the TC‑1 HPV cancer model. PCI also enhanced CD8⁺ T‑cell priming induced by the clinically relevant telomerase vaccine UV1 when combined with poly‑ICLC. For larger protein antigens, including PPD, HBsAg, and KLH, PCI augmented CD4⁺ T‑cell responses and IgG production. Together, these findings establish PCI as a broadly applicable platform for enhancing peptide‑ and protein‑based vaccine immunity in combination with synthetic dsRNA adjuvants.SubjectsBiotechnologyCancerImmunologyMicrobiologyAcknowledgementsWe thank Idun Dale Rein, Unit Leader, and the Flow Cytometry Core Facility at the Institute for Cancer Research, Oslo University Hospital (OUS), for expert support in the design and planning of the experiments presented in Fig. 1. We also thank Ingunn Hagen Westgaard (former Head of Research and Development, Ultimovacs) for valuable scientific input regarding the UV1 vaccine experiments presented in Fig. 4. A.H. and A.B. was supported by The Research Council of Norway (grant numbers: 334178 (Industry PhD); 269817/O20 & 35356/O30 (BIA)); P.K.S. was supported by Helse Sør-Øst (grant number 2017068) and Radforsk (grant number SE0800); PJ received financial support from Swiss Cancer League (grant number: KFS-3451-08-2014) and Swiss National Science Foundation (grant number: CR33I3_162773/1).Author informationAuthors and AffiliationsDepartment of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayPål Kristian Selbo, Arno Bruel, Monika Håkerud, Anne Grete Nedberg, Victoria Tudor Edwards & Kristian BergPCI Biotech AS, Oslo, NorwayArno Bruel, Victoria Tudor Edwards & Anders HøgsetSection for Immunotherapy, Department of Cancer Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayGustav GaudernackDepartment of Dermatology, University Hospital Zurich & University of Zurich, Zurich, SwitzerlandPål JohansenAuthorsPål Kristian SelboView author publicationsSearch author on:PubMed Google ScholarArno BruelView author publicationsSearch author on:PubMed Google ScholarMonika HåkerudView author publicationsSearch author on:PubMed Google ScholarAnne Grete NedbergView author publicationsSearch author on:PubMed Google ScholarVictoria Tudor EdwardsView author publicationsSearch author on:PubMed Google ScholarGustav GaudernackView author publicationsSearch author on:PubMed Google ScholarPål JohansenView author publicationsSearch author on:PubMed Google ScholarKristian BergView author publicationsSearch author on:PubMed Google ScholarAnders HøgsetView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Pål Kristian Selbo.Ethics declarationsCompeting interestsA.H. and P.J. are inventors on patents related to the use of photochemical internalization (PCI) in vaccination. A.B. and A.H. were affiliated with PCI Biotech AS during the conduct of this work. Materials used in the study were supplied by PCI Biotech AS. P.J. has received financial support from PCI Biotech AS. The remaining authors declare no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationRights and permissionsOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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