Immunization with recombinant BCG expressing epitopes from SARS-CoV-2 spike and nuceloprotein protects against infection in hACE-2 murine model

• Grant number: 23/03874-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2023
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Fábio Mambelli Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma, AP.TEM

Abstract

The Severe Acute Respiratory Syndrome caused by SARS-CoV-2 (COVID-19) is one of the most concerning public health problems from recent years. With more than six million deaths worldwide, the development of an effective vaccine and the universal access to the immunizers is still the best strategy to contain its spread. With a significant reduction in the number of deaths and severe cases of the disease achieved with the production and licensing of the first generation of vaccines against COVID-19, the emergence of new variants and the evasion of the protection conferred by these vaccines present themselves as a serious risk factor for a new pandemic wave. In this regard, our group developed an immunization strategy which uses rChimera (a protein developed by our group containing immunodominant epitopes from the N and S proteins from SARS-CoV-2) and the use of Mycobacterium bovis BCG (the most used vaccine worldwide, with an excellent safety standard and known adjuvant action for inducing cellular immunity). We produced a recombinant BCG strain (rBCG-ChD6) which, when used followed by a booster dose containing rChimera and Alum, resulted in the protection of K18-hACE2 mice after challenge by SARS-CoV-2. Initial investigation demonstrated the induction of neutralizing antibodies and strong cellular response in response to the vaccine formulation. Thus, with this project we aim to continue investigating this model by elucidating the protective mechanisms here involved and also to assess if our vaccine is protective against SARS-CoV-2 variants. These data will not only contribute to the field of vaccines against COVID-19, but will also serve as basis for promoting the study of rBCG platforms against other infectious agents.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MAMBELLI, FABIO; DE ARAUJO, ANA CAROLINA V. S. C.; FARIAS, JESSICA P.; DE ANDRADE, KIVIA Q.; FERREIRA, LUIS C. S.; MINOPRIO, PAOLA; LEITE, LUCIANA C. C.; OLIVEIRA, SERGIO C.. An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants. PATHOGENS, v. 14, n. 1, p. 19-pg., 2025-01-01. (23/01925-0, 23/03874-3, 23/09226-3, 17/27131-9, 23/02577-5, 23/11077-6)