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

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Lima-Junior, Josue C. ^{[1, 2]} ; Rodrigues-da-Silva, Rodrigo N. ^[2] ; Banic, Dalma M. ^[3] ; Jiang, Jianlin ^[4] ; Singh, Balwan ^[4] ; Fabricio-Silva, Gustavo M. ^[5] ; Porto, Luis C. S. ^[5] ; Meyer, Esmeralda V. S. ^{[4, 3]} ; Moreno, Alberto ^{[4, 6]} ; Rodrigues, Mauricio M. ^[7] ; Barnwell, John W. ^[8] ; Galinski, Mary R. ^{[4, 6]} ; de Oliveira-Ferreira, Joseli ^[1]

Afiliação do(s) autor(es)

^[1] Inst Oswaldo Cruz, Lab Immunoparasitol, BR-20001 Rio De Janeiro - Brazil

^[2] Oswaldo Cruz Fdn Fiocruz, Ctr Technol Dev Hlth CDTS, Rio De Janeiro - Brazil

^[3] Inst Oswaldo Cruz, Lab Simulideos & Oncocercose, BR-20001 Rio De Janeiro - Brazil

^[4] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 - USA

^[5] Univ Estado Rio De Janeiro, Histocompatibil & Cryopreservat Lab, Rio De Janeiro - Brazil

^[6] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA - USA

^[7] Univ Fed Sao Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, Sao Paulo - Brazil

^[8] CDC Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA - USA

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 7, n. 5 MAY 23 2012.
• Citações Web of Science: 32

Resumo

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. Methods and Findings: 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-3 alpha 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. (AU)

• Processo FAPESP: 09/15132-4 - Geração e análise da imunogenicidade de proteínas recombinantes baseadas nas diferentes formas do antígeno circumsporozoíta de Plasmodium vivax visando o desenvolvimento de uma vacina universal contra malária
• Beneficiário: Maurício Martins Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Temático