Influence of HLA-DRB1 and HLA-DQB1 Alleles on IgG Antibody Response to the P. vivax MSP-1, MSP-3α and MSP-9 in Individuals from Brazilian Endemic Area

Abstract

BackgroundThe antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials.Methods and FindingsIn this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3α and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. The proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1*01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein.ConclusionsHLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.

Immunological markers of Plasmodium vivax exposure and immunity: a systematic review and meta-analysis

“…The full texts of these 162 studies were examined to determine whether they complied with eligibility criteria: 114 did not meet the inclusion criteria (see Additional file 3), 7 fulfilled the inclusion and quality criteria (Figure 1), and 41 studies potentially met inclusion and quality criteria. The authors of the 41 studies that potentially met inclusion and quality criteria were contacted, yielding a further 11 studies that met inclusion and quality criteria, providing a total of 18 studies that were included in the review [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] (Figure 1). Details of these 18 studies are shown in Table 1.…”

“…The studies described by Lima-Junior in 2008 and 2012 [24,26] were conducted in the same area, but the participants were different.…”

“…A total of eight studies investigated responses to PvMSP-1 19 and P. vivax outcomes [22,23,26,27,32,34,39,40].…”

“…Four cross-sectional studies (providing five sets of data) investigated the association between IgG responders to PvMSP-1 19 and P. vivax infection (Figure 4) [22,23,26,39]. Meta-analysis revealed significant heterogeneity between studies (I 2 = 73.8%, P = 0.004), so a pooled estimate was not reported.…”

The role of Vitamin D in malaria

“…The HLA class II controls the immune response to p126-derived amino terminal peptide from P. falciparum [9]. The presence of HLA-DRB1 is associated with severe malaria [10][11][12] and is related to the high frequency of the IgG antibody response to the P. vivax circumsporozoite protein (CSP) and merozoite surface protein (MSP) [13][14][15]. The HLA-DQA alleles are associated with patients co-infected with circumsporozoite variants of P. falciparum in western Thailand [16], and the HLA-DQ1*0502 allele is associated with malaria in the Muong population in Vietnam [17].…”