Evaluation of SARS-CoV-2 escape mutants generated after incubation with antibodies raised by different immunization protocols

• Grant number: 23/02345-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Luiz Mário Ramos Janini
• Grantee: Robert Andreata Santos
• Supervisor: Florian Krammer
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Icahn School of Medicine at Mount Sinai, United States
• Associated to the scholarship: 21/05661-1 - Virological characterization of Brazilian SARS-CoV-2 isolates and their neutralization capabilities by serum from previously infected and/or vaccinated individuals, BP.PD

Abstract

The Coronavirus disease 2019 (COVID-19), is responsible for the second pandemic of this century, according to the World Health Organization. In order to control COVID-19 impact on health, social and economic, several vaccine formulations that were specially aimed to control its severe forms were developed. However, the consecutive emergence of new genetic variants of SARS-CoV-2 have brought new questions and challenges regarding the use of these vaccines, since they are essentially based on the spike glycoprotein from the wild-type strain of SARS-CoV-2. The present project aims to evaluate if the immunization with different protocols can modulate the appearance of new variants of concern. For that purpose, we've obtained 239 serum samples from Brazilian vaccinated volunteers enrolled in CoronaVac (Sinovac), Ad26.COV2S (Janssen), AZD1222 (Oxford-AstraZeneca) and BNT162b2 (BioNTech and Pfizer) immunization protocols employed by the Brazilian government. We previously evaluated the levels of specific antibodies against the receptor biding domain (RBD) and the nucleoprotein (N) of the SARS-CoV-2, as well as the magnitude of neutralization against the wild-type (WT) and Omicron lineages. Such data will allow us to perform a polyclonal-based escape mutant assays based on the vaccination groups. The comparison of the escape mutants generated will allow characterization of groups with lower or higher probability to develop variants of concern after SARS-CoV-2 infection and, consecutively, possibly validate all vaccination methodologies as equally effective, or susceptible, in the control or development of new potentially pandemic SARS-CoV-2 variants. Thus, it is expected that the knowledge generated during this project will contribute to the development of a more efficient tracking of SARS-CoV-2 new variants that can help health agencies worldwide. (AU)