Immune adjuvants aim to boost the effects of immunotherapy. CpG-oligodeoxynucleotide (ODN) Toll-like receptor 9 (TLR9) innate immune agonists are promising immunostimulatory adjuvants; however, poor accumulation into immune cells and lymphoid tissue limits clinical translation.

Associate Professor Howard and his colleagues have developed a recombinant human serum albumin-CpG ODN conjugate technology designed to exploit the neonatal Fc receptor (FcRn)-driven albumin cellular pathway to maximise ODN delivery into TLR9-rich cellular compartments and accumulation in lymph nodes.  

Technology showcased in two new scientific publications    

The iNANO team in collaboration with an interdisciplinary network of national and international partners spanning basic, translational and clinical medicine have recently published their findings in the Journal of Biological Chemistry and Nature Communications. The Journal of Biological Chemistry publication led by the Howard lab in collaboration with partners at Biomedicine, Aarhus University, and at the Spanish National Cancer Research Center introduces the design and describes the FcRn-driven mechanistic basis for its action. It promotes the application of recombinant albumins engineered with different FcRn affinity to tune the effects.   

The second publication in Nature Communications headed by the Team of Professor Jan Terje Andersen, Oslo University applies the technology to a non-invasive subunit vaccine against SARS-CoV-2. The intranasal administered RBD-fused albumin vaccine with the “SupA-Booster” technology built into the design resulted in high immunity in preclinical transgenic mouse models.  

Towards clinical translation for a range of diseases

The technology offers potential use for a wide range of disease types treated with immunotherapy

Ken Howard explains: “SupA-Booster” provides a platform technology that can be used as immune adjuvant added in combination with an antigen or built into an albumin-genetic fusion single design offering versatility and wide applications. We are currently applying the technology in allergy and cancer immunotherapy. This “SupA-Booster” technology platform could result in more effective and safer immunotherapies at reduced doses to the patient. We have secured intellectual protection and working with Aarhus University Technology Transfer and in discussion with potential industrial partners to translate this novel immune adjuvant class”.

About the study (Journal of Biological Chemistry)

Study type:
Experimental biological chemistry

External funding:
This work was funded by Independent Research Fund Denmark, Technology and Production grant 9041-00151A and the Danish Innovation Fund grant 3141-00031A. Financial support was also provided from the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 (PID2020-117323RB-100 and PDC2021-121711-100 to L. A.-V.). J. T. A. was supported by the Research Council of Norway (grant nr. 314909 and 287927), and A. K. A. and J. T. A. by South-Eastern Norway Regional Health Authority (grant nr. 2021069).

Conflicts of interest:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kenneth A Howard and Diego Pilati are co-inventors of a patent application on technology described in the paper.

Link to the scientific article:

10.1016/j.jbc.2025.108508

Diego Pilati, Eugene Kusi Agyei, Marwa Elkhashab, Elisabeth Fuchs, Ian Helstrup Nielsen, Tobias Wang Bjerg, Aina Karen Anthi, Anaïs Jiménez-Reinoso, Marie Beck Iversen, Layla Pohl, Ryo Narita, Susana Frago, Martin R Jakobsen, Jan Terje Andersen, Søren E Degn, Søren R Paludan, Luis Alvarez-Vallina, and Kenneth A Howard

About the study (Nature communications)

Study type:
Experimental biological chemistry

External funding:
This work was partially supported by the Research Council of Norway through its Centers of Excellence scheme, project number 332727, Research Council of Norway grants 267606 (J.T.A., J.N., M.B.), 274993 (F.R.J., J.T.A., J.N., S.B.), 285136 (J.T.A., S.F., S.A.S.), 287872 (G.G., E.T.), 287927 (F.R.J., J.T.A.), 314909 (J.T.A., S.A.S.), South-Eastern Norway Regional Health Authority grants 10357 (J.T.A., F.L-J., A.K.), 2019047 (J.T.A., A.K.), 2019084 (J.T.A., A.K.A.), Independent Research Fund Denmark, Technology and Production grant 9041-00151B (D.P., K.A.H.), MRC (UK; U105181010) a Wellcome Trust Investigator Award (200594/Z/16/Z) and a Wellcome Trust Collaborator Award (214344/A/18/Z). (L.C.J., M.V.), The Coalition for Epidemic Preparedness and Innovation (CEPI) grant to monitor vaccine responses in patients on immunosuppressive therapy (F.L-J.,E.B.V., L.T.) and internal funding from Division of Head, Neck, and Reconstructive Surgery, Oslo University Hospital (T.T.G.).

Conflicts of interest:
I.S., J.T.A. and M.B. are patent co-inventors for “Albumin Variants and Uses Thereof” (EP3063171B1, US10208102, and US10781245). I.S., J.T.A. and T.T.G. have ownership interests in Authera AS. D.P. and K.A.H. are co-inventors of patent WO2024089258A1. The remaining authors declare no competing interests.

Link to the scientific article:

10.1038/s41467-025-59353-6

Aina Karen Anthi, Anette Kolderup, Eline Benno Vaage, Malin Bern, Sopisa Benjakul, Elias Tjärnhage, Fulgencio Ruso-Julve, Kjell-Rune Jensen, Heidrun Elisabeth Lode, Marina Vaysburd, Jeannette Nilsen, Marie Leangen Herigstad, Siri Aastedatter Sakya, Lisa Tietze, Diego Pilati, Mari Nyquist-Andersen, Mirjam Dürkoop, Torleif Tollefsrud Gjølberg, Linghang Peng, Stian Foss, Morten C. Moe, Benjamin E. Low, Michael V. Wiles, David Nemazee, Frode L. Jahnsen, John Torgils Vaage, Kenneth A. Howard, Inger Sandlie, Leo C. James, Gunnveig Grødeland, Fridtjof Lund-Johansen & Jan Terje Andersen

Contact information:
Associate Professor Ken Howard
Aarhus University
Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics 
Email: kenh@inano.au.dk