Dados do Trabalho

Título

Evaluation of the influence of IL-2 -330 G/T (rs2069762) polymorphism on naturally acquired antibodies against components of the malaria vaccine candidate GMZ2.6c (GLURP, MSP-3 and Pfs48/45)

Introdução

Genetic variants such as functional polymorphisms in cytokine encoding genes and its possible influence on a specific immune response buildup poses a great challenge on the development of an effective antimalarial vaccine.

Objetivo(s)

Here we investigated the SNP -330 G/T (rs2069762) located in the Interleukin 2 (IL-2) gene and its influence on naturally acquired antibody levels against Plasmodium falciparum antimalarial vaccine GMZ2.6c components (GLURP, MSP-3 and Pfs48/45).

Material e Métodos

This study was conducted in the malaria endemic areas of Cruzeiro do Sul and Mâncio Lima (Acre state), and Guajará (Amazonas state). A total of 301 samples were genotyped through qPCR using TaqMan® Genotyping Assay kit. The allelic and genotypic frequencies were performed through the TaqMan® Genotyper Software suite. The protein-specific antibodies search assessing the R0 region of GLURP, C-terminal region of MSP-3 and 6c fragment of Pfs48/45 was conducted through ELISA. Statistical evaluation of the SNP influence on total IgG (plus subclasses) and IgM levels was conducted on GraphPad Prism 9.4.

Resultados e Conclusão

Our data shows that (TT) was the most dominant genotype with a frequency of 56.6% (170). The frequency of (GT) and (GG) genotypes was 38.1% (115) and 5.3% (15), respectively. The frequency of the (T) and (G) alleles was 75.7% and 24.3%, respectively. The SNP met the Hardy–Weinberg equilibrium principle (x² 0.348). IgG and IgM against GLURP, MSP-3 and Pfs48/45 were observed in 51.5%, 38% and 26% of the subjects, respectively. Among IgG positive individuals, the IgG1, IgG2, IgG3 and IgG4 frequencies were 31%, 8.5%, 19% and 8.5% for GLURP, 14%, 2%, 8% and 3% for MSP-3 and 9%, 4%, 8% and 4% for Pfs48/45, respectively. Early analysis showed that (GG) genotype bearers presented higher total IgG and IgM levels against GLURP. Increased IgG levels against MSP-3 were also observed in (GG) bearers but no IgM difference was presented. No significant association between genotypes and antibody levels against Pfs48/45 was found.
Early analysis leads to a possible influence of the rs2069762 (GG) genotype against GLURP and MSP-3 antibody response levels. Further analysis will be conducted to evaluate possible individual alleles associations.

Palavras-chave

GLURP; MSP-3; Pfs48/45; Cytokine; Polymorphism; Genotyping; Antibodies; Malaria; Plasmodium falciparum.