Alterations in the blood transcriptome caused by the ChAdOx1 nCoV-19 vaccine in UNIFESP volunteers and genomic and epigenomic variants of SARS-CoV-2 in the State of Sao Paulo

• Grant number: 23/10230-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): September 01, 2023
• Effective date (End): November 30, 2023
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Marcelo Ribeiro da Silva Briones
• Grantee: Cristina Mendes Peter
• Host 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 in Subprojects 3 and 5 described below. The thematic project consists of the deployment 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 Sao Paulo and to use the samples for complementary analyzes to the "Primary and Secondary Outcome Measures", as described in ClinicalTrials.gov (NIH, ID NCT04400838). The general project, coordinated by Prof. Luiz Mario R. Janini, includes Prof. Marcelo R.S. Briones and Prof. Maria Isabel M. Pinto (Discipline of Infectious Diseases, EPM-UNIFESP). The subprojects that integrate thematic project is: (1) establishment of a biorepository of samples from volunteers before and after vaccination, (2) evaluation of the ability to neutralize serum from vaccinated individuals against circulating SARS-CoV-2 strains specific to Brazil and assessment of cross-immunity; (3) characterization of Brazilian SARS-CoV-2 isolates to evaluate vaccine escape potential; (4) analysis of cytokine profiles in serum from volunteers, before and after vaccination, to evaluate 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 whole blood of volunteers, before and after vaccination, to evaluate the type of predominant immune response and possible "priming" by another coronavirus. The specific objectives of this project fall within subprojects 3 and 5, for the genetic and epigenetic analysis of SARS-CoV-2 and the epitranscriptomas of volunteers immunized with the ChAdOx1 nCoV-19 vaccine. For these analyses, we will use direct RNA sequencing, both for viral genomes and for vaccine volunteer transcriptomes. 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 results published with the sequences of SARS-CoV-2 and we are already in the phase of analyzing the epitranscriptome of infected cells. Our objective is to test the hypothesis that in addition to genetic variation between SARS-CoV-2 variants, there is epigenetic variations. Furthermore, we intend to demonstrate the variation in the expression of human genes, before and after vaccination, and their possible epigenetic alterations, such as m6A methylation. This information may help to understand, in more detail, the escape mechanisms of vaccines and the challenge of vaccinated vaccines with different variants. In the long term, the idea is to use the structure set up here to establish the UNIFESP ribogenomics laboratory for the study, without the use of cDNA, of viruses with genomes exclusively made of RNA, such as those that cause influenza, zika, dengue and polio and measles. (AU)