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Immunossenescence and vacinas response: impact of age on the T and B lymphocytes response to SARS-CoV-2 after additional dose of COVID-19 vaccine

Grant number: 22/04632-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2022
Effective date (End): November 30, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Alberto José da Silva Duarte
Grantee:Juliana Ruiz Fernandes
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Even after two years of decreeing the state of a pandemic, epidemiological data indicate that more than 440 million people worldwide have been infected with SARS-CoV-2, leading to approximately 6 million deaths from COVID-19. With the evolution of the vaccination campaign, which in March 2021 had just over 260 thousand vaccinated with the second dose, and an average of new cases of 10 thousand, the 2022 numbers show a decrease in the average of it, reaching little more than 9 thousand cases. Before the advent of vaccines against COVID-19, elderly people over 60 years of age were the most affected by the pandemic event, with significantly higher mortality and morbidity than individuals under 60 years of age. This work aims to evaluate the impact of immunosenescence on the cellular and humoral response to the third dose of the vaccine against COVID-19. The aging process is defined as a progressive decline in homeostasis that occurs after the reproductive phase of life. These changes that accompany increasing age generate dysfunctions in the body's defense against pathogens. Markedly, the immune response in the elderly becomes more restricted due to a decrease in naive cells and an increase in memory cells, and the balance between these responses can affect the effectiveness of protection against infections. T lymphocyte-mediated immunity is not the only one affected. Humoral immunity also suffers from aging consequences being few characteristics with potential importance for the impairment of response, the decrease of responder B lymphocyte subtypes, lower antibody affinity/specificity, and decreased clonal expansion of antibody-producing plasma cells. These characteristics will be evaluated through: immunophenotyping of B lymphocytes (transitional, naive, memory, antibody and IgM secreting) and T lymphocytes (central memory, effector memory, naive, terminally differentiated), evaluation of the specific anti-SARS B cell response -Cov-2 using biotin-streptavidin labeling of the Spike Receptor Binding Domain (RBD) by flow cytometry, evaluation of subpopulations of B and T lymphocytes responding to stimulation in vitro with SARS-Cov-2 peptides, in addition to dosage IgG antibodies and neutralizing antibodies. A cohort of individuals aged 19 to 80 years will be studied. In times of a persistent pandemic, with new variants, in addition to the possibility of new anti-COVID-19 vaccines, given the worse vaccine response related to aging, it becomes crucial the better understand the differential response to the anti-COVID19 vaccine in the elderly, as well as whether the booster dose favors greater vaccine efficacy in this population.

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