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

Josué C Lima-Junior,Mary R Galinski,Maurício M Rodrigues,Jianlin Jiang,Balwan Singh,Esmeralda V S Meyer,Gustavo M Fabrício-Silva,John W Barnwell,Alberto Moreno,Joseli De Oliveira-Ferreira,Rodrigo N Rodrigues-Da-Silva,Luís C S Porto,Dalma M Banic

doi:10.1371/journal.pone.0036419

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.

Highlights

Malaria is one of the most prevalent parasitic diseases in tropical and subtropical countries
Human Leukocyte Antigens (HLA)-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil
During asexual stage development merozoite surface proteins and proteins released from the apical organelles are responsible for the cascade of events involved in the parasite invasion of red blood cells (RBCs) [5]

Summary

Introduction

Malaria is one of the most prevalent parasitic diseases in tropical and subtropical countries. During asexual stage development merozoite surface proteins and proteins released from the apical organelles (rhoptries, micronemes, and dense granules) are responsible for the cascade of events involved in the parasite invasion of red blood cells (RBCs) [5]. In this context, the family of merozoite surface proteins (MSPs) seems to be important for the first contact between merozoites and RBCs and they have become important targets for vaccine development [6,7,8,9]. 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

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Conclusion