Immunopathogenesis of COVID-19 in experimental models and nasal vaccine anti-SARS-CoV-2

• Grant number: 20/06145-4
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2020 - October 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jean Pierre Schatzmann Peron
• Grantee: Jean Pierre Schatzmann Peron
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Claudia Madalena Cabrera Mori ; Francisco Javier Quintana ; Marco Antonio Stephano ; Paola Marcella Camargo Minoprio

Abstract

The world is going through a dramatic moment. The SARS-CoV-2 pandemic has already affected more than 2 million people worldwide, causing about 160,000 deaths so far. COVID-19 is characterized by the onset of fever and cough, which progresses to pneumonia. 1. Studies show that most people experience cold symptoms, which subside after 10-14 days. However, in some patients, the disease may progress to a more severe form, requiring not only hospitalization, but mechanical ventilation. 2. The speed of spread and the severity of the symptoms cause serious public health problems, especially the overcrowding of hospitals, requiring rapid mitigation actions.Severe COVID-19 evolves with acute, bilateral and peripheral pneumonia, evident from alveolar involvement. 2. In fact, both pneumocytes and macrophages express ACE-2, the receptor for viral invasion3. With this, the innate and adaptive mechanisms of the immune response are activated, causing pulmonary inflammation characterized by an intense lympho-monocytic infiltrate and cytokine-storm. 4. Therefore, in addition to controlling viral load, controlling production and cytokines, both play a fundamental role in the outcome of COVID-19.Interestingly, children are not at risk, unlike patients over 60. In fact, lethality in this group can reach 20%. In addition, comorbidities such as hypertension, diabetes, heart disease and pneumopathy increase susceptibility5. This fact is probably due to the increased expression of the viral invasion receptor ACE-26.The knowledge of these mechanisms is essential for us to face the disease effectively. Therefore, the establishment of an experimental model that reproduces the characteristics of human disease is essential. In this context, we propose in this project to study the immunopathogenesis of COVID-19 in two experimental models in C57Bl / 6 hACE-2 mice and hamsters, in addition to testing a nasal vaccine encapsulated in nanoparticles against SARS-CoV-2. Using these models, we will have specific objectives to answer questions that are clinically relevant, and that may actually impact the treatment of the disease. (AU)

Scientific publications

(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)

POLONIO, CAROLINA M.; DA SILVA, PATRICK; RUSSO, FABIELE B.; HYPPOLITO, BRENDO R. N.; ZANLUQUI, NAGELA G.; BENAZZATO, CECILIA; BELTRAO-BRAGA, PATRICIA C. B.; MUXEL, SANDRA M.; PERON, JEAN PIERRE S.. microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 18, p. 19-pg., 2022-09-01. (20/06145-4, 17/11828-0, 17/26170-0, 21/01717-2, 18/16748-8, 17/22504-1, 22/00291-4, 16/07371-2, 19/13731-0)

DE FREITAS, CARLA LONGO; POLONIO, CAROLINA MANGANELI; BRANDAO, WESLEY NOGUEIRA; ROSSATO, CRISTIANO; ZANLUQUI, NAGELA GHABDAN; DE OLIVEIRA, LILIAN GOMES; DE OLIVEIRA, MARILIA GARCIA; EVANGELISTA, LUCILA PIRES; HALPERN, SILVIO; MALUF, MARIANGELA; et al. Human Fallopian Tube - Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System. STEM CELL REVIEWS AND REPORTS, AUG 2021. (20/06145-4, 16/07371-2, 18/10242-5, 17/11828-0, 17/22504-1, 17/26170-0)

POLONIO, CAROLINA MANGANELI; PERON, JEAN PIERRE SCHATZMANN. ZIKV Infection and miRNA Network in Pathogenesis and Immune Response. Viruses-Basel, v. 13, n. 10, OCT 2021. (19/13731-0, 17/26170-0, 20/06145-4, 17/11828-0, 17/22504-1)