Investigation of the hosts' induced elements in response to the immunisation with ChAdOx1 nCOV-19 vaccine in a Phase III Clinical Trial

• Grant number: 20/08943-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2020
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Luiz Mário Ramos Janini
• Grantee: Luiz Mário Ramos Janini
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Principal investigators: Marcelo Ribeiro da Silva Briones ; Maria Isabel de Moraes Pinto
• Associated researchers: Carla Torres Braconi dos Santos ; Daniela Santoro Rosa ; Eduardo Alexandrino Servolo de Medeiros ; Fernando Martins Antoneli Junior ; Gilles Landman ; Ieda Maria Longo Maugéri ; Isabel Maria Vicente Guedes de Carvalho Mello ; Juliana Terzi Maricato ; Lily Yin Weckx ; Marimélia Aparecida Porcionatto ; Mauro José Costa Salles ; Paulo Roberto Abrão Ferreira ; Ricardo Sobhie Diaz
• Associated research grant(s): 24/14354-3 - 35th Brazilian Congress of Virology & 19th MERCOSUR Meeting of Virology, AR.BR
• Associated scholarship(s): 23/14749-5 - HCV genotyping using models based on deep neural networks with Transformer architecture, BP.IC; 23/10230-5 - 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, BP.PD; 23/07287-5 - Assessment of SARS-CoV-2 immune escape by analyzing the immune response of patients hospitalized with moderate or severe COVID-19 during the wave of variant infections Omicron, BP.PD; + associated scholarships 23/08597-8 - Training and technical improvement at Biobanco UNIFESP: quality control of nucleic acids extracted from samples positive for Sars-CoV-2, BP.TT; 23/03792-7 - Evaluation of the growth of different variants of SARS-CoV-2 in permissive cells: Vero CCL-81 and A549, BP.IC; 23/03928-6 - Technical training and improvement at UNIFESP Biobank: enlargement of Sars-CoV-2 positive samples collection, BP.TT; 22/03496-6 - Cytokine profile and immunophenotyping of peripheral blood lymphocytes and myeloid suppressor cells in SARS-CoV-2 vaccinated individuals during episodes of respiratory symptoms: correlation with virus and intensity of clinical manifestations., BP.TT; 21/13111-1 - 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, BP.PD; 21/11236-1 - Blood transcriptome alterations caused by the ChAdOx1 nCoV-19 vaccine in UNIFESP volunteers, BP.TT; 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 - associated scholarships

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 repository for the whole academic community of the São Paulo State. This repository will be converted in a Biobank after the project is concluded, as is stated in current legislation. In addition, the samples stored in the Biorepository 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) to establish a Biorepository containing all samples obtained from volunteers before and after vaccination. This Biorepository will be available, according to legal procedures, to all São Paulo State scientific community as determined by FAPESP guidelines, (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 sera 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 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)

Scientific publications

(21)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAMPOS, JOAO H. C.; MARICATO, JULIANA T.; BRACONI, CARLA T.; ANTONELI, FERNANDO; JANINI, LUIZ MARIO R.; BRIONES, MARCELO R. S.. Direct RNA Sequencing Reveals SARS-CoV-2 m6A Sites and Possible Differential DRACH Motif Methylation among Variants. Viruses-Basel, v. 13, n. 11, NOV 2021. (20/08943-5)

ANTONELI, F.; FURUYAMA, T. N.; CARVALHO, I. M. V. G.; BRIONES, M. R. S.; JANINI, L. M. R.. Temporal data series and logistic models reveal the dynamics of SARS-CoV-2 spike protein D614G variant in the COVID-19 pandemic. Genetics and Molecular Research, v. 20, n. 4, DEC 13 2021. (20/08943-5)

ANDREATA-SANTOS, ROBERT; JANINI, LUIZ M. R.; DURAES-CARVALHO, RICARDO. From Alpha to Omicron SARS-CoV-2 variants: What their evolutionary signatures can tell us?. Journal of Medical Virology, JAN 2022. (21/03684-4, 19/01255-9, 21/05661-1, 20/08943-5)

SOUZA, MILENA SILVA; FARIAS, JESSICA PIRES; ANDREATA-SANTOS, ROBERT; SILVA, MARIANNE PEREIRA; BRITO, RUTH DALETY DA SILVA; DUARTE BARBOSA DA SILVA, MARCIA; PETER, CRISTINA MENDES; CIRILO, MARCUS VINICIUS DE FRANCA; LUIZ, WILSON BARROS; BIRBRAIR, ALEXANDER; et al. Neutralizing antibody response after immunization with a COVID-19 bivalent vaccine: Insights to the future. Journal of Medical Virology, v. 96, n. 2, p. 9-pg., 2024-02-01. (20/06409-1, 23/01925-0, 20/08943-5, 22/11981-1, 21/05661-1, 20/05204-7)

HAYASHI, JACKELINNE Y.; SIMIZO, ADRIANA; MIYAMOTO, JACKSON G.; COSTA, LUCAS V. S.; SOUZA, OLIVIA F.; CHIARELLI, TASSIA; BACAROV, NATALIA B. S.; HIDALGO, RAFAELA; GARCIA, LETICIA D.; SOANE, MICHEL M.; et al. Humoral and cellular responses to vaccination with homologous CoronaVac or ChAdOx1 and heterologous third dose with BNT162b2. Journal of Infection, v. 84, n. 6, p. 3-pg., 2022-06-01. (20/08943-5, 17/20106-9)

ANTONELI, FERNANDO; PETER, CRISTINA M.; BRIONES, MARCELO R. S.. Statistical Distributions of Genome Assemblies Reveal Random Effects in Ancient Viral DNA Reconstructions. Viruses-Basel, v. 17, n. 2, p. 15-pg., 2025-02-01. (20/08943-5)

JOAQUIM SILVA JUNIOR, JOSE VALTER; DURAES-CARVALHO, RICARDO; DE SOUZA, JOELMA RODRIGUES; RAMOS JANINI, LUIZ MARIO; WEIBLEN, RUDI; FLORES, EDUARDO FURTADO. Emergence of SARS-CoV-2 serotype(s): Is it a matter of time?. VIROLOGY, v. 585, p. 4-pg., 2023-06-13. (19/01255-9, 20/08943-5, 21/03684-4)

BARTOLOMEO, CYNTHIA SILVA; LEMES, ROBERTHA MARIANA RODRIGUES; MORAIS, RAFAEL LEITE; PERERIA, GABRIELA CRUZ; NUNES, TAMIRES ALVES; COSTA, ANGELICA JARDIM; MACIEL, RUI MONTEIRO DE BARROS; BRACONI, CARLA TORRES; MARICATO, JULIANA TERZI; JANINI, LUIZ MARIO RAMOS; et al. SARS-CoV-2 infection and replication kinetics in different human cell types: The role of autophagy, cellular metabolism and ACE2 expression. Life Sciences, v. 308, p. 13-pg., 2022-09-07. (20/04709-8, 06/60402-1, 20/06153-7, 20/13480-4, 20/08943-5, 16/20796-2, 19/10922-9)

FUNADA BARBOSA, MIKAELA RENATA; GARCIA, SUZI CRISTINA; BRUNI, ANTONIO DE CASTRO; MACHADO, FLAVIO SILVA; DE OLIVEIRA, ROBERTO XAVIER; DROPA, MILENA; DA COSTA, ANTONIO CHARLYS; LEAL, ELCIO; BRANDAO, CARLOS JESUS; OLIVEIRA DA SILVA, RENAN LOURENCO; et al. One-year surveillance of SARS-CoV-2 in wastewater from vulnerable urban communities in metropolitan Sao Paulo, Brazil. JOURNAL OF WATER AND HEALTH, v. N/A, p. 19-pg., 2022-02-11. (20/08943-5)

CAMPOS, JOAO H. C.; ALVES, GUSTAVO V.; MARICATO, JULIANA T.; BRACONI, CARLA T.; ANTONELI, FERNANDO M.; JANINI, LUIZ MARIO R.; BRIONES, MARCELO R. S.. The epitranscriptome of Vero cells infected with SARS-CoV-2 assessed by direct RNA sequencing reveals m6A pattern changes and DRACH motif biases in viral and cellular RNAs. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 19-pg., 2022-08-16. (20/08943-5, 21/13111-1)

DA COSTA, ANDERSON LUIS; PRIETO-OLIVEIRA, PAULA; DUARTE-BARBOSA, MARCIA; ANDREATA-SANTOS, ROBERT; PETER, CRISTINA M.; DE BRITO, THAMIRES PROLO; ANTONELI, FERNANDO; DURAES-CARVALHO, RICARDO; BRIONES, MARCELO R. S.; MARICATO, JULIANA T.; et al. The Relationship between HERV, Interleukin, and Transcription Factor Expression in ZIKV Infected versus Uninfected Trophoblastic Cells. CELLS, v. 13, n. 17, p. 15-pg., 2024-09-01. (23/07287-5, 23/10230-5, 21/03684-4, 20/08943-5, 21/05661-1, 19/01255-9)

FERREIRA, RENATA C.; ALVES, GUSTAVO V.; RAMON, MARCELLO; ANTONELI, FERNANDO; BRIONES, MARCELO R. S.. Reconstructing Prehistoric Viral Genomes from Neanderthal Sequencing Data. Viruses-Basel, v. 16, n. 6, p. 27-pg., 2024-06-01. (20/08943-5)

FARIAS, JESSICA PIRES; ANDREATA-SANTOS, ROBERT; BRITO, RUTH DALETY DA SILVA; SOUZA, MILENA SILVA; FOGACA, MAYANNA MOREIRA COSTA; PINHEIRO, JOSILENE RAMOS; DA CRUZ, EDGAR FERREIRA; LIANG, WILLIAN; SIMOES, RAFAEL DA CONCEICAO; LUIZ, WILSON BARROS; et al. The fourth COVID-19 vaccine dose increased the neutralizing antibody response against the SARS-CoV-2 Omicron (B.1.1.529) variant in a diverse Brazilian population. MICROBIOLOGY SPECTRUM, v. N/A, p. 16-pg., 2023-11-01. (20/05204-7, 21/05661-1, 20/08943-5, 22/11981-1)

SILVERIO, BRUNA STEFANIE; DURO, RODRIGO LOPES SANZ; DE SOUSA, LARISSA LEAO F.; GUILARDI, MARIANA DIAS; CABRAL-MIRANDA, GUSTAVO; JANINI, LUIZ MARIO RAMOS; DURAES-CARVALHO, RICARDO. Detection and Phylogenetic Analysis of Emerging Human-Associated Gemykibivirus-2 in Molossus molossus Bat From Brazil. Journal of Medical Virology, v. 97, n. 1, p. 4-pg., 2025-01-01. (19/14526-0, 20/05146-7, 23/04038-4, 21/03684-4, 24/09079-3, 19/01255-9, 20/08943-5)

CAMPOS, JOAO H. C.; AGUILAR, ANA C. R.; ANTONELI, FERNANDO; TRUZZI, GISELLE; BRIONES, MARCELO R. S.; FERREIRA, RENATA C.; COELHO, FERNANDO M. S.. Whole-genome analysis of monozygotic Brazilian twins discordant for type 1 narcolepsy: a case report. BMC Neurology, v. 22, n. 1, p. 8-pg., 2022-11-18. (20/08943-5, 21/13111-1)

NUNES, JOAO PEDRO DA SILVA; SILVA, MARIANGELA DE OLIVEIRA; APOSTOLICO, JULIANA DE SOUZA; DAHER, ISABELA PAZOTTI; MARQUES, RODOLFO FERREIRA; YAMAMOTO, MARCIO MASSAO; CARVALHO, ALEXIA ADRIANNE VENCESLAU BRITO; DE CASTRO-AMARANTE, MARIA FERNANDA; DURIGON, EDISON LUIZ; WRENGER, CARSTEN; et al. Adjuvant combination and antigen multimerization shape neutralizing antibody and T cell responses to a SARS-CoV-2 RBD subunit vaccine. FRONTIERS IN IMMUNOLOGY, v. 16, p. 21-pg., 2025-07-17. (20/08943-5, 21/13004-0, 15/26722-8)

REGO, LAYANE SOUZA; FAVARO, MARIANNA TEIXEIRA PINHO; RODRIGUES-JESUS, MONICA JOSIANE; ANDREATA-SANTOS, ROBERT; JANINI, LUIZ MARIO RAMOS; SECKLER, MARCELO MARTINS; FERREIRA, LUIS CARLOS DE SOUZA; AZZONI, ADRIANO RODRIGUES. Amino Compound-Synthesized Gold Nanoparticles for SARS-CoV-2 Antigen Delivery. PHARMACEUTICS, v. 17, n. 9, p. 15-pg., 2025-09-17. (23/01153-7, 20/05204-7, 21/05661-1, 20/08943-5, 23/16234-2, 20/10700-3)

DA SILVA, VITOR GABRIEL LOPES; SCHMITZ, GABRIELA JUSTAMANTE HANDEL; SULLIVAN, KATHLEEN E.; BARBATE, JULIA; AZINAR, MARIA IZABEL DE HARO; ARANDA, CAROLINA SANCHEZ; DE MORAES-PINTO, MARIA ISABEL. Enhanced T-cell immunity and lower humoral responses following 5-dose SARS-CoV-2 vaccination in patients with inborn errors of immunity compared with healthy controls. FRONTIERS IN IMMUNOLOGY, v. 16, p. 14-pg., 2025-03-06. (20/08943-5, 21/13419-6)

CLARK, JORDAN J.; HOXIE, IRENE; ADELSBERG, DANIEL C.; SAPSE, IDEN A.; ANDREATA-SANTOS, ROBERT; YONG, JEREMY S.; AMANAT, FATIMA; TCHEOU, JOHNSTONE; RASKIN, ARIEL; SINGH, GAGANDEEP; et al. Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination. CELL REPORTS, v. 43, n. 11, p. 21-pg., 2024-11-05. (21/05661-1, 23/02345-7, 20/08943-5)

ANDREATA-SANTOS, ROBERT; MACHADO, RAFAEL RAHAL GUARAGNA; DOS SANTOS ALVES, RUBENS PRINCE; SALES, NATIELY SILVA; SOARES, CAMILA PEREIRA; RODRIGUES, KARINE BITENCOURT; SILVA, MARIANGELA OLIVEIRA; FAVARO, MARIANNA TEIXEIRA DE PINHO; RODRIGUES-JESUS, MONICA JOSIANE; YAMAMOTO, MARCIO MASSAO; et al. Validation of Serological Methods for COVID-19 and Retrospective Screening of Health Employees and Visitors to the Sao Paulo University Hospital, Brazil. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 8-pg., 2022-06-02. (20/08943-5, 16/20045-7, 21/05661-1, 14/50890-5, 16/23560-0, 15/02352-7, 20/06409-1, 17/24769-2, 16/14344-1, 18/23680-0, 20/10700-3, 18/07629-5, 18/07142-9)

RODRIGUES-JESUS, MONICA JOSIANE; FAVARO, MARIANNA TEIXEIRA DE PINHO; VENCESLAU-CARVALHO, ALEXIA ADRIANNE; DE CASTRO-AMARANTE, MARIA FERNANDA; ALMEIDA, BIANCA DA SILVA; SILVA, MARIANGELA DE OLIVEIRA; ANDREATA-SANTOS, ROBERT; BARBOSA, CECILIA GOMES; BRITO, SAMANTHA CARVALHO MAIA; FREITAS-JUNIOR, LUCIO H.; et al. Nano-multilamellar lipid vesicles promote the induction of SARS-CoV-2 immune responses by a protein-based vaccine formulation. Nanomedicine-Nanotechnology Biology and Medicine, v. 45, p. 11-pg., 2022-08-31. (20/10700-3, 20/08943-5, 16/23560-0, 20/05204-7, 21/05661-1)