On the adjuvanticity of hyaluronan: The case of a SARS-CoV-2 vaccine
Vaccines based on mRNA have been fundamental in facing the COVID-19 pandemic, however, they still raise concerns about stability and long-term efficacy. Thus, protein-based vaccines remain valid options and hence the study of effective adjuvants is crucial. Here, we developed a COVID-19 vaccine based on the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein, which is covalently conjugated to the natural polymer hyaluronan (HA) that acts as an immunological adjuvant. Vaccination of K18-hACE2 mice with HA-RBD was well tolerated, and elicited high and sustained titres of RBD-binding antibodies and SARS-CoV-2-neutralizing antibodies, without the addition of other immunostimulatory compounds. Most importantly, HA-RBD vaccination conferred long-term protection to K18-hACE2 mice after challenge with SARS-CoV-2, also in the case of two consequent infections driven by different variants. These findings demonstrate the efficacy of HA-based vaccination against COVID-19 disease, and support the promising use of HA as an efficient and well tolerated adjuvant.
Authors
- Debora Carpanese (ORCID: https://orcid.org/0000-0001-7002-1665)
- Silvia Dalla Santa (ORCID: https://orcid.org/0000-0002-5616-6494)
- Antonella Grigoletto (ORCID: https://orcid.org/0000-0001-9679-0083)
- Filippo Torrigiani (ORCID: https://orcid.org/0000-0002-2601-684X)
- Gaia Zuccolotto (ORCID: https://orcid.org/0000-0002-2002-8807)
- Vito Barbieri (ORCID: https://orcid.org/0000-0002-8349-6704)
- Gianfranco Pasut (ORCID: https://orcid.org/0000-0002-8754-0899)
- Francesco Bonfante
- Antonio Rosato (ORCID: https://orcid.org/0000-0002-5263-8386)
- Roberta Sommaggio (ORCID: https://orcid.org/0000-0002-5682-5867)
- Alessandro Sinigaglia (ORCID: https://orcid.org/0000-0002-2386-1757)
- Ranieri Verin (ORCID: https://orcid.org/0000-0001-9366-5682)
- Bruno Martorelli Di Genova (ORCID: https://orcid.org/0000-0001-9983-1856)
- Matteo Pagliari (ORCID: https://orcid.org/0000-0003-0199-5647)
- Anna Dalla Pietà (ORCID: https://orcid.org/0000-0002-7875-7914)
- Luisa Barzon (ORCID: https://orcid.org/0000-0003-0720-8456)
- Alessandro Penna (ORCID: https://orcid.org/0000-0002-0016-6196)
- Anna Tosi (ORCID: https://orcid.org/0000-0002-4890-0169)
- Tamini Sofia
- Stefania Vogiatzis
Institutions
- University of Padua (IT)
- Istituto Oncologico Veneto (IT)
- Istituto Zooprofilattico Sperimentale delle Venezie (IT)
Publication Details
- Journal
- Journal of Controlled Release
- Published
- 2025-03-31
- DOI
- https://doi.org/10.1016/j.jconrel.2025.113674
- Citations
- 2
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Horizon 2020