A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4+ and CD8+ T Cell Responses

被引:36
|
作者
Rosa, Daniela Santoro [1 ,3 ,4 ]
Ribeiro, Susan Pereira [1 ,3 ]
Almeida, Rafael Ribeiro [1 ]
Mairena, Eliane Conti [2 ,3 ]
Postol, Edilberto [2 ,3 ]
Kalil, Jorge [1 ,2 ,3 ]
Cunha-Neto, Edecio [1 ,2 ,3 ]
机构
[1] Univ Sao Paulo, Sch Med, Div Clin Immunol & Allergy, Dept Med,Lab Clin Immunol & Allergy LIM60, Sao Paulo, Brazil
[2] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil
[3] Inst Invest Immunol INCT, Sao Paulo, Brazil
[4] Fed Univ Sao Paulo UNIFESP, Div Immunol, Sao Paulo, Brazil
来源
PLOS ONE | 2011年 / 6卷 / 02期
基金
巴西圣保罗研究基金会;
关键词
SIMIAN IMMUNODEFICIENCY VIRUS; PROTECTIVE IMMUNITY; ELITE CONTROLLERS; RHESUS-MONKEYS; CENTRAL MEMORY; INFECTION; CHALLENGE; STEP; PREDICTION; CORRELATE;
D O I
10.1371/journal.pone.0016921
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+) T cells are important for the generation and maintenance of functional CD8(+) cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4(+) T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+)/CD8(+) T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+) and CD8(+) T cells that proliferate and produce any two cytokines (IFN gamma/TNF alpha, IFN gamma/IL-2 or TNF alpha/IL-2) simultaneously in response to HIV-1 peptides. For CD4(+) T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFN gamma/TNF alpha/IL-2). The vaccine also generated long-lived central and effector memory CD4(+) T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+) T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+) T cells and antibody responses-elicited by other HIV immunogens.
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页数:13
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