Avaliação da resposta imune celular multifuncional induzida pela SpiN-Tec MCTI/UFMG como reforço na vacinação heteróloga contra COVID–19

Abstract

The present study evaluates the multifunctional cellular immune response induced by SpiN-Tec MCTI UFMG, an innovative recombinant protein vaccine against SARS-CoV-2. Its antigen combines the virus’ Spike protein receptor-binding domain (RBD) to the complete sequence of the nucleocapsid protein (N). The vaccine was administered to volunteers with no history of COVID-19 and who had been previously immunized with two doses of CoronaVac and a booster dose of CoronaVac. Peripheral blood samples were collected on the day of vaccine administration, before the shot was given (time V0), and then after 14 (V14) and 28 days (V28). Mononuclear cells were isolated and cultivated in cell culture medium containing either the N or the S protein from SARS-CoV-2 and the SpiN antigenic protein itself. The frequency and phenotype of antigen-specific immune cells were assessed by flow cytometry. A robust functional response, mediated by the production of the cytokines IFN-γ, TNF and IL-2, confirmed the activation of CD4+ and CD8+ T cells. The induction of such Th1 profile response led to the expansion of central and effector memory T cells. Furthermore, the SpiN protein demonstrated to be a more potent cellular stimulus to cytokine production by CD4+ T cells than the N and S protein by themselves. Finally, a large population of double-negative T cells (CD3+CD4–CD8–) was induced. These cells responded to the viral antigens and also secreted cytokines, indicating a possible effector function. The phenotype of these cells should be explored further in future studies, since they appear as a potentially additional mechanism of protection provided by the vaccine. Given the need for annual administration of booster shots to recurrently stimulate the immune memory against SARS-CoV-2, especially effective through heterologous immunization, the development of a vaccine fully produced with national resources and capable of inducing a robust humoral and cellular immune response is a great advantage for the Brazilian public health. This study demonstrated that the SpiN-Tec MCTI UFMG is an immunogenic vaccine and it is capable of stimulating an effective immune response, with potential to be a candidate for vaccination against COVID-19.