Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil
Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil.
The study was carried out in Paragominas, Pará State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-119) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-γ and IL-10 were measured by enzyme-linked immunosorbent assay.
The prevalence of activated CD4+ was greater than CD8+ T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-119 and PSS1 antigen. A low proliferative response against PvMSP-119 and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-γ and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-119 stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient’s cells while low levels of IFN-γ and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-119 was evidenced, regardless class or IgG subclass.PvMSP-119-induced antibodies were predominantly on non-cytophilic subclasses.
The results presented here shows that PvMSP-119 was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-119 in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate.
- WHO: World Malaria Report 2012. Geneva: World Health Organization; 2012. http://www.who.int/malaria/publications/world_malaria_report_2012/en/
- Barcus MJ, Basri H, Picarima H, Manyakori C, Sekartuti , Elyazar I, Bangs MJ, Maguire JD, Baird JK: Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in northeastern Indonesian Papua. Am J Trop Med Hyg 2007, 77:984–991.
- Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, Lampah DA, Price RN: Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med 2008, 5:e128. CrossRef
- Genton B, D’Acremont V, Rare L, Baea K, Reeder JC, Alpers MP, Muller I: Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea. PLoS Med 2008, 5:e127. CrossRef
- Kochar DK, Das A, Kochar SK, Saxena V, Sirohi P, Garg S, Kochar A, Khatri MP, Gupta V: Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India. Am J Trop Med Hyg 2009, 80:194–198.
- Anstey NM, Russell B, Yeo TW, Price RN: The pathophysiology of vivax malaria. Trends Parasitol 2009, 25:220–227. CrossRef
- Alexandre MA, Ferreira CO, Siqueira AM, Magalhães BL, Mourão MP, Lacerda MV, Alecrim MG: Severe Plasmodium vivax malaria, Brazilian Amazon. Emerg Infect Dis 2010, 16:1611–1614. CrossRef
- Manning L, Laman M, Law I, Bona C, Aipit S, Teine D, Warrell J, Rosanas-Urgell A, Lin E, Kiniboro B, Vince J, Hwaiwhanje I, Karunajeewa H, Michon P, Siba P, Mueller I, Davis TM: Features and prognosis of severe malaria caused by Plasmodium falciparum Plasmodium vivax and mixed Plasmodium species in Papua New Guinean children. PLoS One 2011, 6:e29203. CrossRef
- Yadav D, Chandra J, Aneja S, Kumar V, Kumar P, Dutta AK: Changing profile of severe malaria in north Indian children. Indian J Pediatr 2012, 79:483–487. CrossRef
- Lacerda MV, Mourão MP, Alexandre MA, Siqueira AM, Magalhães BM, Martinez-Espinosa FE, Filho FS, Brasil P, Ventura AM, Tada MS, Couto VS, Silva AR, Silva RS, Alecrim MG: Understanding the clinical spectrum of complicated Plasmodium vivax malaria: a systematic review on the contributions of the Brazilian literature. Malar J 2012, 11:12. CrossRef
- SVS: Boletim Epidemiológico da Malária. 2012. http://portal.saude.gov.br/portal/arquivos/pdf/boletim_malaria_2010_2011.pdf
- Cruz-Gallardo I, Diaz-Moreno I, Diaz-Quintana A, Donaire A, Velazquez-Campoy A, Curd RD, Rangachari K, Birdsall B, Ramos A, Holder AA, De la Rosa MA: Antimalarial activity of cupredoxins: the interaction of Plasmodium merozoite surface protein 1 19 (MSP-1 19 ) and Rusticyanin. J Biol Chem 2013, 288:20896–20907. CrossRef
- Blackman MJ, Heidrich HG, Donachie S, McBride JS, Holder AA: A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. J Exp Med 1990, 172:379–382. CrossRef
- Holder AA, Blackman MJ, Burghaus PA, Chappel JA, Ling IT, McCallum-Deighton N, Shai S: A malaria merozoite surface protein (MSP1)-structure, processing and function. Mem Inst Oswaldo Cruz 1992, 87:37–42. CrossRef
- Gerold P, Schofield L, Blackman MJ, Holder AA, Schwarz RT: Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the merozoite surface proteins-1 and -2 of Plasmodium falciparum . Mol Biochem Parasitol 1996, 75:131–143. CrossRef
- Soares IS, Levitus G, Souza JM, Del Portillo HA, Rodrigues MM: Acquired immune responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1 in individuals exposed to malaria. Infect Immun 1997, 65:1606–1614.
- Soares IS, Oliveira SG, Souza JM, Rodrigues MM: Antibody response to the N and C-terminal regions of the Plasmodium vivax merozoite surface protein 1 in individuals living in an area of exclusive transmission of P. vivax malaria in the north of Brazil. Acta Trop 1999, 72:13–24. CrossRef
- Park JW, Moon SH, Yeom JS, Lim KJ, Sohn MJ, Jung WC, Cho YJ, Jeon KW, Ju W, Ki CS, Oh MD, Choe K: Naturally acquired antibody responses to the C-terminal region of merozoite surface protein 1 of Plasmodium vivax in Korea. Clin Diagn Lab Immunol 2001, 8:14–20.
- Rodrigues MH, Cunha MG, Machado RL, Ferreira OC Jr, Rodrigues MM, Soares IS: Serological detection of Plasmodium vivax malaria using recombinant proteins corresponding to the 19-kDa C-terminal region of the merozoite surface protein-1. Malar J 2003, 2:39. CrossRef
- Morais CG, Soares IS, Carvalho LH, Fontes CJ, Krettli AU, Braga EM: IgG isotype to C-terminal 19 kDa of Plasmodium vivax merozoite surface protein 1 among subjects with different levels of exposure to malaria in Brazil. Parasitol Res 2005, 95:420–426. CrossRef
- Wickramarachchi T, Illeperuma RJ, Perera L, Bandara S, Holm I, Longacre S, Handunnetti SM, Udagama-Randeniya PV: Comparison of naturally acquired antibody responses against the C-terminal processing products of Plasmodium vivax merozoite surface protein-1 under low transmission and unstable malaria conditions in Sri Lanka. Int J Parasitol 2007, 37:199–208. CrossRef
- Barbedo MB, Ricci R, Jimenez MC, Cunha MG, Yazdani SS, Chitnis CE, Rodrigues MM, Soares IS: Comparative recognition by human IgG antibodies of recombinant proteins representing three asexual erythrocytic stage vaccine candidates of Plasmodium vivax . Mem Inst Oswaldo Cruz 2007, 102:335–339. CrossRef
- Mourão LC, Morais CG, Bueno LL, Jimenez MC, Soares IS, Fontes CJ, Guimarães Lacerda MV, Xavier MS, Barnwell JW, Galinski MR, Braga EM: Naturally acquired antibodies to Plasmodium vivax blood-stage vaccine candidates (PvMSP-1 19 and PvMSP-3α 359–798 and their relationship with hematological features in malaria patients from the Brazilian Amazon. Microbes Infect 2012, 14:730–739. CrossRef
- Lima-Junior JC, Rodrigues-da-Silva RN, Banic DM, Jiang J, Singh B, Fabrício-Silva GM, Porto LC, Meyer EV, Moreno A, Rodrigues MM, Barnwell JW, Galinski MR, de Oliveira-Ferreira J: 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. PLoS One 2012, 7:e36419. CrossRef
- Yang C, Collins WE, Sullivan JS, Kaslow DC, Xiao L, Lal AA: Partial protection against Plasmodium vivax blood-stage infection in Saimiri monkeys by immunization with a recombinant C-terminal fragment of merozoite surface protein 1 in block copolymer adjuvant. Infect Immun 1999, 67:342–349.
- Ling IT, Ogun SA, Holder AA: Immunization against malaria with a recombinant protein. Parasite Immunol 1994, 16:63–67. CrossRef
- Daly TM, Long CA: Humoral response to a carboxyl-terminal region of the merozoite surface protein-1 plays a predominant role in controlling blood-stage infection in rodent malaria. J Immunol 1995, 155:236–243.
- Holder AA, Guevara Patiño JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, Blackman MJ: Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia 1999, 41:409–414.
- Hirunpetcharat C, Tian JH, Kaslow DC, van Rooijen N, Kumar S, Berzofsky JA, Miller LH, Good MF: Complete protective immunity induced in mice by immunization with the 19-kilodalton carboxyl-terminal fragment of the merozoite surface protein-1 (MSP-1 19 ) of Plasmodium yoelii expressed in Saccharomyces cerevisiae: correlation of protection with antigen-specific antibody titer, but not with effector CD4+ T cells. J Immunol 1997, 159:3400–3411.
- Hirunpetcharat C, Stanisic D, Liu XQ, Vadolas J, Strugnell RA, Lee R, Miller LH, Kaslow DC, Good MF: Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP-1 19 ) induces protective immunity to blood stage malaria infection in mice. Parasite Immunol 1998, 20:413–420. CrossRef
- Ichino Y, Ishikawa T: Effects of cryopreservation on human lymphocyte functions: comparison of programmed freezing method by a direct control system with a mechanical freezing method. J Immunol Methods 1985, 77:283–290. CrossRef
- Schmid I, Uittenbogaart CH, Keld B, Giorgi JV: A rapid method for measuring apoptosis and dual-color immunofluorescence by single laser flow cytometry. J Immunol Methods 1994, 170:145–157. CrossRef
- Trager W, Jensen JB: Human malaria parasites in continuous culture. Science 1976, 193:673–675. CrossRef
- Riccio EKP, Neves-Júnior I, Riccio LRP, Banic DM, Daniel-Ribeiro CT, Ferreira-da-Cuz MF: Cryopreservation of peripheral blood mononuclear cells does not affect the levels of spontaneous apoptosis after 24h culture. Cryobiology 2002, 45:127–134. CrossRef
- Weinberg A, Song LY, Wilkening C, Sevin A, Blais B, Louzao R, Stein D, Defechereux P, Durand D, Riedel E, Raftery N, Jesser R, Brown B, Keller MF, Dickover R, McFarland E, Fenton T: Optimization and limitations of use of cryopreserved peripheral blood mononuclear cells for functional and phenotypic T-cell characterization. Clin Vaccine Immunol 2009, 16:1176–1186. CrossRef
- Torre D, Speranza F, Giola M, Matteelli A, Tambini R, Biondi G: Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria. Clin Diagn Lab Immunol 2002, 9:348–351.
- Quin SJ, Seixas EM, Cross CA, Berg M, Lindo V, Stockinger B, Langhorne J: Low CD4(+) T cell responses to the C-terminal region of the malaria merozoite surface protein-1 may be attributed to processing within distinct MHC class II pathways. Eur J Immunol 2001, 31:72–81. CrossRef
- Mukherjee P, Devi YS, Chauhan VS: Blood stage malaria antigens induce different activation-induced cell death programs in splenic CD4 + T cells. Parasite Immunol 2008, 30:497–514. CrossRef
- Green DR, Droin N, Pinkoski M: Activation-induced cell death in T cells. Immunol Rev 2003, 193:70–81. CrossRef
- Ho M, Schollaardt T, Snape S, Looareesuwan S, Suntharasamai P, White NJ: Endogenous interleukin-10 modulates proinflammatory response in Plasmodium falciparum malaria. J Infect Dis 1998, 178:520–525. CrossRef
- Day NP, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TT, Mai NT, Phu NH, Sinh DX, White NJ, Ho M: The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J Infect Dis 1999, 180:1288–1297. CrossRef
- Walther M, Woodruff J, Edele F, Jeffries D, Tongren JE, King E, Andrews L, Bejon P, Gilbert SC, De Souza JB, Sinden R, Hill AV, Riley EM: Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes. J Immunol 2006, 177:5736–5745.
- Li C, Sanni LA, Omer F, Riley E, Langhorne J: Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10-deficient mice are ameliorated by anti-tumor necrosis factor alpha and exacerbated by anti-transforming growth factor beta antibodies. Infect Immun 2003, 71:4850–4856. CrossRef
- Couper KN, Blount DG, Riley EM: IL-10: the master regulator of immunity to infection. J Immunol 2008, 180:5771–5777.
- Rosario AP F d, Langhorne J: T cell-derived IL-10 and its impact on the regulation of host responses during malaria. Int J Parasitol 2012, 42:549–555. CrossRef
- O’Donnell RA, Saul A, Cowman AF, Crabb BS: Functional conservation of the malaria vaccine antigen MSP-119across distantly related Plasmodium species. Nat Med 2000, 6:91–95. CrossRef
- Putaporntip C, Jongwutiwes S, Sakihama N, Ferreira MU, Kho WG, Kaneko A, Kanbara H, Hattori T, Tanabe K: Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus. Proc Natl Acad Sci USA 2002, 99:16348–16353. CrossRef
- Gowda DC: TLR-mediated cell signaling by malaria GPIs. Trends Parasitol 2007, 23:596–604. CrossRef
- McGregor IA, Barr M: Antibody response to tetanus toxoide inoculation in malarious and non-malarious Gambian children. Trans R Soc Trop Med Hyg 1962, 56:364–367. CrossRef
- Ho M, Webster HK, Looareesuwan S, Supanaranond W, Phillips RE, Chanthavanich P, Warrell DA: Antigen-specific immunosuppression in human malaria due to Plasmodium falciparum . J Infect Dis 1986, 3:763–771. CrossRef
- Oliveira-Ferreira J, Pratt-Riccio LR, Arruda M, Santos F, Ribeiro CT, Goldberg AC, Banic DM: HLA class II and antibody responses to circumsporozoite protein repeats of P. vivax (VK210, VK247 and P. vivax -like) in individuals naturally exposed to malaria. Acta Trop 2004, 92:63–69. CrossRef
- Pratt-Riccio LR, Lima-Junior JC, Carvalho LJ, Theisen M, Espindola-Mendes EC, Santos F, Oliveira-Ferreira J, Goldberg AC, Daniel-Ribeiro CT, Banic DM: Antibody response profiles induced by Plasmodium falciparum glutamate-rich protein in naturally exposed individuals from a brazilian area endemic for malaria. Am J Trop Med Hyg 2005, 73:1096–1103.
- Carpenter D, Abushama H, Bereczky S, Färnert A, Rooth I, Troye-Blomberg M, Quinnell RJ, Shaw MA: Immunogenetic control of antibody responsiveness in a malaria endemic area. Hum Immunol 2007, 68:165–169. CrossRef
- Storti-Melo LM, da Costa DR, Souza-Neiras WC, Cassiano GC, Couto VS, Póvoa MM, Soares Ida S, de Carvalho LH, Arevalo-Herrera M, Herrera S, Rossit AR, Cordeiro JA, de Mattos LC, Machado RL: Influence of HLA-DRB-1 alleles on the production of antibody against CSP, MSP-1, AMA-1, and DBP in Brazilian individuals naturally infected with Plasmodium vivax . Acta Trop 2012, 121:152–155. CrossRef
- Sabbagh A, Courtin D, Milet J, Massaro JD, Castelli EC, Migot-Nabias F, Favier B, Rouas-Freiss N, Moreau P, Garcia A, Donadi EA: Association of HLA-G 3′ untranslated region polymorphisms with antibody response against Plasmodium falciparum antigens: preliminary results. Tissue Antigens 2013, 82:53–58. CrossRef
- Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY: IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 1998, 160:3555–3561.
- Fernandes AA, Carvalho LJ, Zanini GM, Ventura AM, Souza JM, Cotias PM, Silva-Filho IL, Daniel-Ribeiro CT: Similar cytokine responses and degrees of anemia in patients with Plasmodium falciparum and Plasmodium vivax infections in the Brazilian Amazon region. Clin Vaccine Immunol 2008, 15:650–658. CrossRef
- Cerávolo IP, Bruña-Romero O, Braga EM, Fontes CJ, Brito CF, Souza JM, Krettli AU, Adams JH, Carvalho LH: Anti- Plasmodium vivax duffy binding protein antibodies measure exposure to malaria in the Brazilian Amazon. Am J Trop Med Hyg 2005, 72:675–681.
- Tran TM, Oliveira-Ferreira J, Moreno A, Santos F, Yazdani SS, Chitnis CE, Altman JD, Meyer EV, Barnwell JW, Galinski MR: Comparison of IgG reactivities to Plasmodium vivax merozoite invasion antigens in a Brazilian Amazon population. Am J Trop Med Hyg 2005, 73:244–255.
- Bereczky S, Montgomery SM, Troye-Blomberg M, Rooth I, Shaw MA, Färnert A: Elevated anti-malarial IgE in asymptomatic individuals is associated with reduced risk for subsequent clinical malaria. Int J Parasitol 2004, 34:935–942. CrossRef
- Mehrizi AA, Zakeri S, Rafati S, Salmanian AH, Djadid ND: Immune responses elicited by co-immunization of Plasmodium vivax and P. falciparum MSP-1 using prime-boost immunization strategies. Parasite Immunol 2011, 33:594–608. CrossRef
- Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- September 2013
- Online ISSN
- BioMed Central
- Additional Links
- Plasmodium vivax
- Cellular response
- Author Affiliations
- 11. Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil, CEP: 21040-900
- 12. Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal), Fiocruz, Reference Center for Malaria in the Extra-Amazonian Region for the Secretary for Health Surveillance from the Ministry of Health, Rio de Janeiro, RJ, Brazil
- 13. Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil
- 14. Departamento de Análises Clínicas e Toxicológicas, Universidade de São Paulo, São Paulo, Brazil
- 15. Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil
- 16. Programa de Ensaios Clínicos em Malária - Instituto Evandro Chagas, SVS, Belém, Brazil