Análise de polimorfismo de base única (SNV) em genes do inflamassoma de NLRP1, NLRP3 e citocinas IL- 1 Beta e IL-18 em indivíduos vacinados com a Coronavac

Abstract

More than 3 years since the start of the pandemic, the SARS-CoV-2 virus has recorded more than 700 million cumulative cases of infections with approximately 6 million deaths worldwide. In Brazil, there are 37 million, with more than 700 thousand deaths. Vaccination against COVID-19 is used as a prevention mechanism, providing the individual with protection against serious forms of the disease. In studies that evaluate the effectiveness of vaccines, the divergence of the immunological response profile among individuals vaccinated against COVID-19 is notable. Among the factors that may contribute to this difference in vaccine responses are genetic factors, which can contribute to different immunological responses to the virus by individuals. Single nucleotide polymorphisms in inflammasome genes are frequently described in the literature as associated with susceptibility, predisposition and protection to various diseases, and may be related to different immune responses to vaccination and immunogenetic studies that evaluate possible associations of genetic variants with vaccine efficacy are scarce. . For this reason, the present work analyzed single base polymorphisms (SNVs) in NLRP3 inflammasome genes (rs10754558, rs10802502, rs3803265), NLRP1 (rs12150220, rs35865013, rs2670660) by real-time quantitative PCR and IL-1beta cytokines (rs16944 ) and IL18 (rs187238), by polymerase chain-restriction fragment length polymorphism in individuals vaccinated with CoronaVac, in order to analyze possible associations with the humoral response profile presented by immunized individuals. Data and samples from 385 participants were analyzed, including 193 professionals from the HEMOAM Foundation vaccinated with two doses of the CoronaVac vaccine and 192 healthy controls. Samples from vaccinated individuals were collected at three times, at time 0 (pre-vaccine T0 n= 193), 30 days (T1 n=193) and 90 days (T2 n=193) after the second dose, for genotyping and quantification. of neutralizing antibodies. The results demonstrated differences in the humoral immune response profile presented by vaccinated individuals, with a decline in the production of neutralizing antibodies 90 days after administration of the second dose. We observed statistical differences related to the increase and maintenance of neutralizing antibody production at the three times, associated with the polymorphism for IL1Brs16944 T/T genotype (T0, T/T vs. C/T p=0.039; T1, T/T vs. . C/T p=0.001; T2, T/T vs. C/T p=0.021), NLRP1 rs12150220 T/T genotype (T1, T/T vs. A/A, p= 0.007), NLRP3 rs10802502 C genotype /C (T1, T/T vs. C/C, p=0.016; T2, T/T vs. C/C, p= 0.032, NLRP3 rs3806265 genotype C/T and T/T (T1 C/C vs. C/ T p=0.031; T/T vs. C/C p= 0.045; T2 C/C vs. C/T p= 0.009; T/T vs. C/C, p=0.020, while the C/T IL- genotypes 1β rs16944, A/A NLRP1 12150220, T/T NLRP3 10802502 and C/C 3806265 seem to influence a decreased production of antibodies, which may be related to low antibody titers in individuals immunized with CoronaVac.