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.
BACKGROUND
The 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.


RESULTS
In 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.


CONCLUSIONS
HLA-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.
Laboratory of Immunoparasitology, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Josué C
JC
Lima-Junior
Rodrigo N
RN
Rodrigues-da-Silva
Dalma M
DM
Banic
Jianlin
J
Jiang
Balwan
B
Singh
Gustavo M
GM
Fabrício-Silva
Luís C S
LC
Porto
Esmeralda V S
EV
Meyer
Alberto
A
Moreno
Maurício M
MM
Rodrigues
John W
JW
Barnwell
Mary R
MR
Galinski
Joseli
J
de Oliveira-Ferreira
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000953:Antigens, Protozoan / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D002648:Child; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007407:Interviews as Topic; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D008875:Middle Aged; D015995:Prevalence; D015800:Protozoan Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D000953:Antigens, Protozoan; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D007074:Immunoglobulin G; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C089133:merozoite surface protein 3, Plasmodium; C455300:merozoite surface protein 9, Plasmodium