Mapping of genomic and epigenomic variants of SARS-CoV-2 in the State of São Paulo and alterations in the blood transcriptome associated with the ChAdOx1 nCoV-19 vaccine in UNIFESP volunteers

• Grant number: 21/13111-1
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): December 01, 2021
• Effective date (End): November 30, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal researcher: Luiz Mário Ramos Janini
• Grantee: João Henrique Coelho Campos
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 20/08943-5 - Investigation of the hosts' induced elements in response to the immunisation with ChAdOx1 nCOV-19 vaccine in a Phase III Clinical Trial, AP.TEM

Abstract

This proposal is part of the ongoing FAPESP thematic project (20/08943-5). The PD fellow will work directly on subprojects 3 and 5 described below. The thematic project consists of the unfolding of the international project with 2,000 samples of volunteers from the Oxford-UNIFESP test of the ChAdOx1 nCoV-19 vaccine. The objective is to establish a repository for the entire academic community of the State of São Paulo and use the samples for complementary analyzes to "Primary and Secondary Outcome Measures", as described in ClinicalTrials.gov (NIH, ID NCT04400838). The general project is coordinated by Prof. Luiz Mario R. Janini, from the Department of Microbiology, Immunology, and Parasitology at Escola Paulista de Medicina/EPM/UNIFESP. The subprojects that integrate the thematic project are (1) establishment of a biorepository of samples from volunteers before and after vaccination; (2) evaluation of the neutralization capacity of sera from individuals vaccinated against specific circulating SARS-CoV-2 strains in Brazil and cross-immunity assessment; (3) characterization of Brazilian isolates of SARS-CoV-2 to assess potential vaccine escape; (4) analysis of cytokine profiles in volunteer sera, before and after vaccination, to assess the inflammatory response and associated effects; (5) analysis of the blood transcriptomes of volunteers before and after vaccination; and (6) analysis of the secretome profile in the volunteers' whole blood, before and after vaccination, to assess the predominant type of immune response and possible "priming" by another coronavirus. The specific objectives of this project fit into subprojects 3 and 5, for genetic and epigenetic analysis of SARS-CoV-2 and epitranscriptomes of volunteers immunized with the ChAdOx1 nCoV-19 vaccine. For these analyzes, we will use direct RNA sequencing, both for viral genomes and for transcriptomes of vaccine volunteers. Our group is a pioneer in Brazil in direct RNA sequencing (ribogenomics) for mapping genetic and epigenetic differences in SARS-CoV-2. We already have published results with the SARS-CoV-2 sequences, and we are already in the phase of analysis of the epitranscriptome of infected cells. We aim to test the hypothesis that, in addition to genetic variation among SARS-CoV-2 variants, there are epigenetic variations. Furthermore, we intend to show the variation in the expression of human genes, before and after vaccination, and its possible epigenetic alterations, such as m6A methylation. This information can contribute to understanding, in more detail, the escape mechanisms of vaccines and the challenge of vaccines immunized with different variants. In the long term, the idea is to use the structure set up here to establish the ribogenomics laboratory at UNIFESP for the study, without the use of cDNA, of viruses with exclusively RNA genomes, such as those that cause Influenza, Zika, dengue, and Poliomyelitis and Measles. (AU)