RESUMO
Malaria remains a public health challenge. Since many control strategies have proven ineffective in eradicating this disease, new strategies are required, among which the design of a multivalent vaccine stands out. However, the effectiveness of this strategy has been hindered, among other reasons, by the genetic diversity observed in parasite antigens. In Plasmodium vivax, the Erythrocyte Binding Protein (PvEBP, also known as DBP2) is an alternate ligand to Duffy Binding Protein (DBP); given its structural resemblance to DBP, EBP/DBP2 is proposed as a promising antigen for inclusion in vaccine design. However, the extent of genetic diversity within the locus encoding this protein has not been comprehensively assessed. Thus, this study aimed to characterize the genetic diversity of the locus encoding the P. vivax EBP/DBP2 protein and to determine the evolutionary mechanisms modulating this diversity. Several intrapopulation genetic variation parameters were estimated using 36 gene sequences of PvEBP/DBP2 from Colombian P. vivax clinical isolates and 186 sequences available in databases. The study then evaluated the worldwide genetic structure and the evolutionary forces that may influence the observed patterns of genetic variation. It was found that the PvEBP/DBP2 gene exhibits one of the lowest levels of genetic diversity compared to other vaccine-candidate antigens. Four major haplotypes were shared worldwide. Analysis of the protein's 3D structure and epitope prediction identified five regions with potential antigenic properties. The results suggest that the PvEBP/DBP2 protein possesses ideal characteristics to be considered when designing a multivalent effective antimalarial vaccine against P. vivax.
Assuntos
Antígenos de Protozoários , Variação Genética , Vacinas Antimaláricas , Malária Vivax , Plasmodium vivax , Proteínas de Protozoários , Plasmodium vivax/genética , Plasmodium vivax/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Humanos , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/genética , Malária Vivax/prevenção & controle , Malária Vivax/parasitologia , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Colômbia , Filogenia , Receptores de Superfície CelularRESUMO
Immunoglobulin G (IgG) is an essential antibody in adaptive immunity; a differential expansion of the gene encoding the Fc region (IGHG) of this antibody has been observed in mammals. Like humans, animal biomedical models, such as mice and macaques, have four functional genes encoding 4 IgG subclasses; however, the data for New World monkeys (NWM) seems contentious. Some publications argue for the existence of a single-copy gene for IgG Fc; however, a recent paper has suggested the presence of IgG subclasses in some NWM species. Here, we evaluated the genetic distances and phylogenetic relationships in NWM to assess the presence of IgG subclasses using the sequences of IGHG genes from 13 NWM species recovered from genomic data and lab PCR and cloning-based procedures available in GenBank. The results show that several sequences do not cluster into the expected taxon, probably due to cross-contamination during laboratory procedures, and consequently, they appear to be wrongly assigned. Additionally, several sequences reported as subclasses were shown to be 100% identical in the CH domains. The data presented here suggests that there is not enough evidence to establish the presence of IgG subclasses in NWM.
