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Evaluation of the humoral and cellular protective potentials of vaccines against SARS-CoV-2 different lineages

Grant number: 19/13552-8
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): November 01, 2019
Effective date (End): July 31, 2023
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Alessandro dos Santos Farias
Grantee:Natália Brunetti Silva
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was discovered in December 2019 in Wuhan, China, and quickly spread across the globe due to its ability to transmit before symptoms manifest, causing the pandemic as Coronavirus 2019 disease (COVID-19). Until October 7, 2021, the virus was able to infect around 236 million individuals and causes the death of 4.8 million. Brazil is the third country with the highest number of cases and the second with the highest number of deaths. SARS-CoV-2 is known to primarily infect the respiratory tract. However, little is known about the immune response to this pathogen and which factors influence the severity and evolution of the disease. The proven lack of prophylactic and direct eradication drugs of the new Coronavirus and the need to contain COVID-19 made it necessary to create effective vaccines. The concentration of global financial resources, as well as the technological and scientific advances in the area in recent decades, have made it possible for the development and testing times of vaccines against SARS-CoV-2 to be reduced from about 10 years to just a few months, with 318 vaccines developed so far. Previous studies combating zoonotic epidemics, such as those caused by the SARS-CoV and MERS-CoV Coronaviruses, enabled the identification of the antigenic target, a viral Spike surface protein, specifically its receptor-binding domain (RBD). It is a highly variable region that can undergo mutations due to selective pressure mediated by antibodies, which can affect infectivity, viral load, and virus transmissibility. The emergence of SARS-CoV-2 variants with mutations in the RBD domain is a concern for the scientific community regarding the control of the pandemic, as it may compromise the humoral immune response, via antibody neutralization and the success of programs of vaccination around the world. Despite having proven effective in combating COVID-19 and reducing the number of severe cases, little is known about the humoral and cellular protective potential of these vaccines applied with the virus and its variant lineages. In a study published in a selective editorial policy journal, our research group, in collaboration with other researchers, observed that the P.1 lineage of the new Coronavirus can escape the neutralization of antibodies from convalescent patients and individuals previously immunized with the CoronaVac and that this neutralization capacity is six times smaller when compared to the original lineage of SARS-CoV-2. Cellular responses mediated by CD4+ and CD8+ T lymphocytes are believed to play an important role in modulating disease severity. Thus, the antigen-specific immune response mustn't be compromised by mutations originating in variant lineages of SARS-CoV-2, ensuring the effectiveness of immunization programs. Given the above, it is our objective to evaluate the neutralizing potential of antibodies generated by vaccines against different lineages of SARS-CoV-2 circulating in Brazil and other aspects of the humoral immune response. As well as the generation of memory cells and the reactivity of antigen-specific T lymphocytes. (AU)

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