A self-adjuvanted VLPs-based Covid-19 vaccine proven versatile, safe, and highly protective

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Vuitika, Larissa ; Cortes, Nelson ; Malaquias, Vanessa B. ; Silva, Jaqueline D. Q. ; Lira, Aline ; Prates-Syed, Wasim A. ; Schimke, Lena F. ; Luz, Daniela ; Duraes-Carvalho, Ricardo ; Balan, Andrea ; Camara, Niels O. S. ; Cabral-Marques, Otavio ; Krieger, Jose E. ; Hirata, Mario H. ; Cabral-Miranda, Gustavo

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 14, n. 1, p. 17-pg., 2024-10-16.

Abstract

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 beta) 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 beta 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 mu g and 50 mu g stimulated the production of neutralizing antibodies. In in vivo testing, the group of animals vaccinated with 50 mu g of vaccine formulation provided complete protection against virus infection, maintaining stable body weight without showing signs of disease. In conclusion, the Q beta 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. (AU)

• FAPESP's process: 19/14526-0 - Development of vaccines against Streptococcus pyogenes and Chikungunya Virus based on virus like particles
• Grantee: Gustavo Cabral de Miranda
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/08468-8 - Development of VLPs-based vaccines against SARS-CoV-2 and other human Coronaviruses
• Grantee: Wasim Aluísio Prates Syed
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/04667-3 - Development of vaccines against Streptococcus pyogenes and Chikungunya Virus based on virus like particles
• Grantee: Gustavo Cabral de Miranda
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 21/03102-5 - Development of safe and effective vaccines against the Chikungunya Virus based on homologous and heterologous VLPs
• Grantee: Aline Aparecida de Lima Lira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/09404-0 - Development of vaccine anti-SARS-CoV-2 based on VLPs
• Grantee: Larissa Vuitika
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/03508-1 - Development of an effective and safe anti-Zika Virus vaccine using chimeric VLPs expressing Envelope Domain III (E-DIII) protein
• Grantee: Nelson Côrtes de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)