Immunogenicity of Butantan Institute produced COVD-19 vaccines in non-obese type 2 diabetes mellitus

• Grant number: 24/08439-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rui Curi
• Grantee: Mariana Cruz Lazzarin
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is one of the predominant comorbidities among non-surviving COVID-19 patients. Diabetic patients exhibit a reduced immunogenic response to vaccines for infectious diseases in general. In Brazil, over 75% of type 2 diabetics are overweight or obese. Obesity itself affects the body's response to vaccines. The Butantan Institute produces two COVID-19 vaccines, the widely administered CORONAVAC and NDV-HXP-S (Butanvac), which are still in the clinical study phase. In this project, we propose to investigate the exclusive influence of the diabetic state, without the obesity factor, on the dose-response relationship to these COVID-19 vaccines. This study aims to evaluate the humoral and cellular immunogenicity of CORONAVAC and NDV-HXP-S vaccines in an experimental model for non-obese DM2. Male Wistar and Goto-Kakizaki rats (non-obese DM2 experimental model) of 8 weeks will be used. The animals will be distributed into six experimental groups (n=10): control+saline, control+CORONAVAC, control+Butanvac, diabetic+saline, diabetic+CORONAVAC, diabetic+Butanvac. Immunization will be administered with three doses of CORONAVAC and NDV-HXP-S vaccines at 15-day intervals via intramuscular injection. Inflammatory profile will be assessed by measuring the cytokines EGF, CCL 11, CX3CL1, G-CSF, GRO/KC, IFN-³, IL-1±, IL-1², IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17A, IL-18, IP-10, Leptin, LIX, MCP-1, MIP-1±, MIP-2, RANTES, TNF-±, VEGF using the multiplex method. Humoral immunogenicity will be assessed by determining IgG titers for the S protein of the SARS-CoV-2 virus and virus neutralization tests by neutralizing antibodies. The cellular response will be evaluated through immunophenotyping via flow cytometry of SARS-CoV-2 specific T and B lymphocytes and identification of Th1, Th2 e regulatory T cells through intracellular detection of cytokines IFN-³, IL-4, and IL-10. Additionally, histopathological analyses of lymphoid organs will be conducted to identify possible histological alterations associated with immunization. Immunohistochemical analysis will be performed to investigate the expression of specific markers for different cellular subpopulations in lymphoid organs, such as CD3+, CD20+, CD68+, CD4+, CD8+, and CD34+, and cellular proliferation by the Ki-67 marker. These comprehensive analyses will allow a complete assessment of the animal's immune response to the tested vaccines. This study will enable the determination of the Butantan Institute's COVID-19 vaccine that elicits the best immunogenic response in type 2 diabetic animals without the effects of obesity.