title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil CEP: 21040-900. mffcruz@ioc.fiocruz.br.
authors.forename: Evelyn K P
authors.initials: EK
authors.lastname: Riccio
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Totino
authors.forename: Lilian R
authors.initials: LR
authors.lastname: Pratt-Riccio
authors.forename: Vitor
authors.initials: V
authors.lastname: Ennes-Vidal
authors.forename: Irene S
authors.initials: IS
authors.lastname: Soares
authors.forename: Maurício Martins
authors.initials: MM
authors.lastname: Rodrigues
authors.forename: José Maria
authors.initials: JM
authors.lastname: de Souza
authors.forename: Cláudio Tadeu
authors.initials: CT
authors.lastname: Daniel-Ribeiro
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Ferreira-da-Cruz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000913:Antibodies, Protozoan / Q000097:blood*; D001938:Brazil / Q000453:epidemiology; D049109:Cell Proliferation; D002648:Child; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016780:Malaria, Vivax / Q000453:epidemiology*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D010966:Plasmodium vivax / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020066:Merozoite Surface Protein 1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma
references.citation: Am J Trop Med Hyg. 2005 Dec;73(6):1096-103
references.pmid: 16354819
references.citation: PLoS One. 2012;7(5):e36419
references.pmid: 22649493
references.citation: J Immunol. 2008 May 1;180(9):5771-7
references.pmid: 18424693
references.citation: Immunol Rev. 2003 Jun;193:70-81
references.pmid: 12752672
references.citation: Tissue Antigens. 2013 Jul;82(1):53-8
references.pmid: 23745572
references.citation: J Infect Dis. 1999 Oct;180(4):1288-97
references.pmid: 10479160
references.citation: Parasitol Res. 2005 Apr;95(6):420-6
references.pmid: 15759156
references.citation: Mem Inst Oswaldo Cruz. 1992;87 Suppl 3:37-42
references.pmid: 1343716
references.citation: Int J Parasitol. 2012 May 15;42(6):549-55
references.pmid: 22549022
references.citation: PLoS Med. 2008 Jun 17;5(6):e128
references.pmid: 18563962
references.citation: Clin Vaccine Immunol. 2009 Aug;16(8):1176-86
references.pmid: 19515870
references.citation: Am J Trop Med Hyg. 2005 Aug;73(2):244-55
references.pmid: 16103583
references.citation: Clin Diagn Lab Immunol. 2002 Mar;9(2):348-51
references.pmid: 11874876
references.citation: J Immunol. 2006 Oct 15;177(8):5736-45
references.pmid: 17015763
references.citation: Acta Trop. 1999 Jan 15;72(1):13-24
references.pmid: 9924957
references.citation: Clin Diagn Lab Immunol. 2001 Jan;8(1):14-20
references.pmid: 11139190
references.citation: Int J Parasitol. 2007 Feb;37(2):199-208
references.pmid: 17055511
references.citation: Mem Inst Oswaldo Cruz. 2007 Jun;102(3):335-9
references.pmid: 17568939
references.citation: Infect Immun. 1999 Jan;67(1):342-9
references.pmid: 9864235
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16348-53
references.pmid: 12466500
references.citation: Acta Trop. 2012 Feb;121(2):152-5
references.pmid: 22107686
references.citation: Am J Trop Med Hyg. 2009 Feb;80(2):194-8
references.pmid: 19190212
references.citation: Am J Trop Med Hyg. 2007 Nov;77(5):984-91
references.pmid: 17984364
references.citation: Acta Trop. 2004 Sep;92(1):63-9
references.pmid: 15301976
references.citation: Int J Parasitol. 2004 Jul;34(8):935-42
references.pmid: 15217732
references.citation: Microbes Infect. 2012 Aug;14(9):730-9
references.pmid: 22445906
references.citation: Malar J. 2003 Nov 14;2(1):39
references.pmid: 14617378
references.citation: Hum Immunol. 2007 Mar;68(3):165-9
references.pmid: 17349871
references.citation: Malar J. 2012 Jan 09;11:12
references.pmid: 22230294
references.citation: J Immunol. 1995 Jul 1;155(1):236-43
references.pmid: 7602100
references.citation: Am J Trop Med Hyg. 2005 Jun;72(6):675-81
references.pmid: 15964949
references.citation: PLoS One. 2011;6(12):e29203
references.pmid: 22216212
references.citation: Emerg Infect Dis. 2010 Oct;16(10):1611-4
references.pmid: 20875292
references.citation: Eur J Immunol. 2001 Jan;31(1):72-81
references.pmid: 11169440
references.citation: J Immunol Methods. 1994 Apr 15;170(2):145-57
references.pmid: 8157993
references.citation: J Immunol. 1998 Apr 1;160(7):3555-61
references.pmid: 9531318
references.citation: Trends Parasitol. 2007 Dec;23(12):596-604
references.pmid: 17980663
references.citation: J Immunol. 1997 Oct 1;159(7):3400-11
references.pmid: 9317139
references.citation: J Exp Med. 1990 Jul 1;172(1):379-82
references.pmid: 1694225
references.citation: Infect Immun. 1997 May;65(5):1606-14
references.pmid: 9125537
references.citation: J Infect Dis. 1986 Apr;153(4):763-71
references.pmid: 2936834
references.citation: J Immunol Methods. 1985 Mar 18;77(2):283-90
references.pmid: 3981006
references.citation: Infect Immun. 2003 Sep;71(9):4850-6
references.pmid: 12933825
references.citation: Cryobiology. 2002 Oct;45(2):127-34
references.pmid: 12482378
references.citation: Trends Parasitol. 2009 May;25(5):220-7
references.pmid: 19349210
references.citation: Parasite Immunol. 1994 Feb;16(2):63-7
references.pmid: 8015856
references.citation: Mol Biochem Parasitol. 1996 Jan;75(2):131-43
references.pmid: 8992312
references.citation: Parasite Immunol. 2008 Oct;30(10):497-514
references.pmid: 18643960
references.citation: PLoS Med. 2008 Jun 17;5(6):e127
references.pmid: 18563961
references.citation: Parasite Immunol. 2011 Nov;33(11):594-608
references.pmid: 21883290
references.citation: J Biol Chem. 2013 Jul 19;288(29):20896-20907
references.pmid: 23749994
references.citation: Indian J Pediatr. 2012 Apr;79(4):483-7
references.pmid: 22090254
references.citation: Clin Vaccine Immunol. 2008 Apr;15(4):650-8
references.pmid: 18256207
references.citation: J Infect Dis. 1998 Aug;178(2):520-5
references.pmid: 9697735
references.citation: Parassitologia. 1999 Sep;41(1-3):409-14
references.pmid: 10697894
references.citation: Science. 1976 Aug 20;193(4254):673-5
references.pmid: 781840
references.citation: Nat Med. 2000 Jan;6(1):91-5
references.pmid: 10613831
references.citation: Parasite Immunol. 1998 Sep;20(9):413-20
references.pmid: 9767608