Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune response associated with HLA-A and -B supertypes in Chagasic chronic patients from Mexico

被引：29

作者：

Villanueva-Lizama, Liliana E. ^{[1
,2
,3
]}

Cruz-Chan, Julio V. ^{[1
,2
,3
]}

Aguilar-Cetina, Amaru del C. ^{[1
]}

Herrera-Sanchez, Luis F. ^{[4
]}

Rodriguez-Perez, Jose M. ^{[5
]}

Rosado-Vallado, Miguel E. ^{[1
]}

Ramirez-Sierra, Maria J. ^{[1
]}

Ortega-Lopez, Jaime ^{[6
]}

Jones, Kathryn ^{[2
,3
]}

Hotez, Peter ^{[2
,3
,7
,8
]}

Bottazzi, Maria Elena ^{[2
,3
,8
]}

Dumonteil, Eric ^{[1
,9
]}

机构：

[1] Univ Autonoma Yucatan, Ctr Invest Reg Dr Hideyo Noguchi, Lab Parasitol, Merida, Yucatan, Mexico

[2] Baylor Coll Med, Dept Pediat, Texas Childrens Hosp, Ctr Vaccine Dev, Houston, TX 77030 USA

[3] Baylor Coll Med, Natl Sch Trop Med, Houston, TX 77030 USA

[4] Univ Autonoma Yucatan, Fac Med, Unidad Cardiometab, Merida, Yucatan, Mexico

[5] Inst Nacl Cardiol Ignacio Chavez, Dept Biol Mol, Mexico City, DF, Mexico

[6] Inst Politecn Nacl, Dept Biotecnol & Bioingn, Ctr Invest & Estudios Avanzados, Mexico City, DF, Mexico

[7] Rice Univ, James A Baker Inst Publ Policy 3, Houston, TX USA

[8] Baylor Univ, Dept Biol, Waco, TX 76798 USA

[9] Tulane Univ, Dept Trop Med, Sch Publ Hlth & Trop Med, Vector Borne Infect Dis Res Ctr, New Orleans, LA 70118 USA

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2018年 / 12卷 / 01期

关键词：

THERAPEUTIC DNA VACCINE; CD8(+) T-CELLS; DISEASE PATIENTS; HUMAN INFECTION; CLASS-I; CARDIOMYOPATHY; MICE; CD4(+); IDENTIFICATION; MANAGEMENT;

D O I：

10.1371/journal.pntd.0006240

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immuno-phenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA(-)CCR7(-)). These cells also produced IFN-gamma and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-gamma production by CD4(+) and CD8(+) T cells and CD8(+) proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic vaccine against Chagas disease.

引用

页数：21