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Viral characterization of Brazilian isolates of SARS-CoV-2 and study of sequence variation and evolutionary patterns of Spike protein to evaluate potential vaccine escape by target or epitope modification

Grant number: 21/05661-1
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2021
Effective date (End): June 30, 2023
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal researcher:Luiz Mário Ramos Janini
Grantee:Robert Andreata Santos
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 research proposal consists of a "spin-off" project based on volunteer samples of the Oxford-UNIFESP ChAdOx1 nCoV-19 vaccine trial. The proposal will involve the 1,000 volunteer samples, and corresponding time points, to primarily establish a collection of samples for the whole academic community of the São Paulo State. This collection will be stored in the Biobank stablished at UNIFESP, as is stated in current legislation. In addition, the samples stored in the Biobank will be used to perform analysis of these samples that do not overlap with the "Primary and Secondary Outcome Measures" as described in the clinical trial documentation available in ClinicalTrials.gov (National Institutes of Health, ID NCT04400838). This project will be coordinated by Prof. Luiz Mario Janini and will include a team of principal investigators in different areas pertaining to the specific objectives and research track record at FAPESP. The objectives of this project are: (1) store and provide all samples obtained from volunteers before and after vaccination at UNIFESP's Biobank. This Biobank was built in accordance with legal procedures, with the objective of correctly storing and making samples available to the entire scientific community of the State of São Paulo, nationally and internationally, (2) to evaluate the neutralizing capacity of sera from vaccinated subjects against Brazilian-specific circulating SARS-CoV-2 strains and other Brazilian specific strains of coronavirus for assessment of cross immunity, (3) to characterize Brazilian specific isolates of SARS-CoV-2 and study the sequence variation and evolutionary patterns of the SARS-CoV-2 Spike protein in to assess the potential of vaccine escape by modification of the target or epitopes, (4) to generate and analyze cytokine profiles of serum from volunteers before and after vaccination to evaluate the inflammatory response and associated effects, (5) To analyze and compare the blood transcriptomes of volunteers, by RNA-seq, before and after vaccination. This analysis will be quantitative and qualitative to evaluate the impact of the vaccine on differential gene expression levels and assess 3 the individual variation in genetic response to the vaccine and (6) To analyze the whole blood secretome profiles of volunteers, before and after vaccination, to assess the predominant type of immune response and priming by another coronavirus. (AU)

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