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

• Type of Material: Article
• Authors: Josue C. Lima-Junior, Instituto Oswaldo Cruz; Rodrigo N. Rodrigues-da-Silva, Oswaldo Cruz Foundation (Fiocruz); Dalma M. Banic, Instituto Oswaldo Cruz; Jianlin Jiang, Emory University; Balwan Singh, Emory University; Gustavo M. Fabricio-Silva, Rio de Janeiro State University; Luis C. S. Porto, Rio de Janeiro State University; Esmerelda V. S. Meyer, Instituto Oswaldo Cruz; C. Moreno, Emory University; Mauricio M. Rodrigues, Universidade Federal de São Paulo; John W. Barnwell, CDC/National Center for Infectious Diseases; Mary Galinski, Emory University; Joseli de Oliveira-Ferreira, Instituto Oswaldo Cruz
• Language: English
• Date: 2012-05-23
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Lima-Junior et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0036419
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 5
• Start Page: e36419
• End Page: e36419
• Grant/Funding Information: This work was supported by Brazilian National Research Council – CNPq/PAPES, (Conselho Nacional de Desenvolvimento Científico e Tecnológico/Programa de Apoio Pesquisa Estratégica em Sade) Fiocruz, FAPESP (Foundation for Research Support of the State of São Paulo) 2009/15132-4 and INCTV-CNPq, (The National Institute for Vaccine Technology) National Institute of Health, the Yerkes National Primate Research Center Base Grant # RR00165 awarded by the National Center for Research Resources of the National Institutes of Health, and NIH Grants #RO1 AI0555994. Josué da Costa Lima Junior was the recipient of a CAPES/Fiocruz Fellowship.
• Keywords: IMMUNE-RESPONSES; MEROZOITE SURFACE PROTEIN-1; FALCIPARUM; MULTIDISCIPLINARY SCIENCES; HLA CLASS-II; MALARIA PARASITES; Science & Technology - Other Topics; IMMUNOGENIC PROPERTIES; Science & Technology; VACCINE; Multidisciplinary Sciences; C-TERMINAL REGIONS; PLASMODIUM-VIVAX; CIRCUMSPOROZOITE PROTEIN
• Research Categories: Health Sciences, Immunology; Health Sciences, Epidemiology

Abstract

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-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.