1 Department of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, QC H3T 1J4, Canada.
2 Centre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
3 Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
4 Sainte-Justine Research Centre, Montreal, QC H3T 1C5, Canada.
5 Department of Chemistry and Biochemistry and Centre for NanoScience Research, Concordia University, Montreal, QC H3T 1J4, Canada.
6 Research and Development Branch, Defence Therapeutics Inc., Montreal, QC H4S 1Z9, Canada.
7 Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC H3T 1J4, Canada.
8 SPR-MS Facility, Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada.
9 Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
10 Department of Biomedical & Molecular Sciences, Queen's University, Kingston, ON K7L 3J8, Canada.
11 Molecular Biology Program, Université de Montréal, Montreal, QC H3T 1J4, Canada.

Despite the recent control of COVID-19, the devastating effects caused by the 3-year pandemic highlight the importance of developing effective vaccines to rapidly address future outbreaks. The present study describes a novel Spike (Sp) protein-based vaccine formulation using the Accum platform. Although Sp-Accum bioconjugation does not alter the overall protein structure, it triggers a substantial antibody titer: i) exhibiting higher specificity toward the S1 domain of Sp, ii) neutralizing Sp-ACE2 interactions, and iii) cross-reacting with various Sp variants. Besides validating the vaccine immunogenicity in rabbits, its administration in a "gold-standard" SARS-CoV-2 hamster model was shown to be safe while accelerating viral clearance without eliciting signs of pathological inflammation in the lungs of infected animals. Altogether, this proof-of-concept study not only demonstrates once again the versatility of the Accum technology in vaccine engineering, but it provides an enabling technology for the rapid development of value-added, protein-based vaccines for future pandemics.