A self-adjuvanted VLPs-based Covid-19 vaccine proven versatile, safe, and highly protective.
Larissa Vuitika, Nelson C��rtes, Vanessa B Malaquias, Jaqueline D Q Silva, Aline Lira, Wasim A Prates-Syed, Lena F Schimke, Daniela Luz, Ricardo Dur��es-Carvalho, Andrea Balan, Niels O S C��mara, Otavio Cabral-Marques, Jos�� E Krieger, Mario H Hirata, Gustavo Cabral-Miranda
Author Information
Larissa Vuitika: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Nelson C��rtes: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Vanessa B Malaquias: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, S��o Paulo, Brazil.
Jaqueline D Q Silva: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Aline Lira: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Wasim A Prates-Syed: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Lena F Schimke: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Daniela Luz: Laboratory of Bacteriology, Butantan Institute, S��o Paulo, Brazil.
Ricardo Dur��es-Carvalho: S��o Paulo School of Medicine, Department of Microbiology, Immunology and Parasitology, Federal University of S��o Paulo (UNIFESP), S��o Paulo, SP, Brazil.
Andrea Balan: Applied Structural Biology Laboratory, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, 05508-000, Brazil.
Niels O S C��mara: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Otavio Cabral-Marques: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil.
Jos�� E Krieger: Heart Institute, Clinical Hospital, Faculty of Medicine, Laboratory of Genetics and Molecular Cardiology, Clinical Hospital, Faculty of Medicine, University of S��o Paulo, S��o Paulo, Brazil.
Mario H Hirata: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, S��o Paulo, Brazil.
Gustavo Cabral-Miranda: Department of Immunology, Institute of Biomedical Sciences, University of S��o Paulo, S��o Paulo, Brazil. gcabral.miranda@usp.br.
Vaccination has played a critical role in mitigating Covid-19. Despite the availability of licensed vaccines, there remains a pressing need for improved vaccine platforms that provide high protection, safety, and versatility, while also reducing vaccine costs. In response to these challenges, our aim is to create a self-adjuvanted vaccine against SARS-CoV-2, utilizing Virus-Like Particles (VLPs) as the foundation. To achieve this, we produced bacteriophage (Q��) VLPs in a prokaryotic system and purified them using a rapid and cost-effective strategy involving organic solvents. This method aims to solubilize lipids and components of the cell membrane to eliminate endotoxins present in bacterial samples. For vaccine formulation, Receptor Binding Domain (RBD) antigens were conjugated using chemical crosslinkers, a process compatible with Good Manufacturing Practice (GMP) standards. Transmission Electron Microscopy (TEM) confirmed the expected folding and spatial configuration of the Q��VLPs vaccine. Additionally, vaccine formulation assessment involved SDS-PAGE stained with Coomassie Brilliant Blue, Western blotting, and stereomicroscopic experiments. In vitro and in vivo evaluations of the vaccine formulation were conducted to assess its capacity to induce a protective immune response without causing side effects. Vaccine doses of 20 ��g and 50 ��g stimulated the production of neutralizing antibodies. In in vivo testing, the group of animals vaccinated with 50 ��g of vaccine formulation provided complete protection against virus infection, maintaining stable body weight without showing signs of disease. In conclusion, the Q��VLPs-RBD vaccine has proven to be effective and safe, eliminating the necessity for supplementary adjuvants and offering a financially feasible approach. Moreover, this vaccine platform demonstrates flexibility in targeting Variants of Concern (VOCs) via established conjugation protocols with VLPs.
