The presence of T cell epitopes is important for induction of antibody responses against antigens directed to DEC205+ dendritic cells

被引:22
作者
Amorim, Kelly N. S. [1 ]
Rampazo, Eline V. [1 ]
Antonialli, Renan [1 ]
Yamamoto, Marcio M. [1 ]
Rodrigues, Mauricio M. [2 ,3 ]
Soares, Irene S. [3 ,4 ]
Boscardin, Silvia B. [1 ,3 ]
机构
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Lab Antigen Targeting Dendrit Cells, BR-05508000 Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, CTCMol, BR-04044010 Sao Paulo, Brazil
[3] Natl Inst Sci & Technol Vaccines, BR-31270910 Belo Horizonte, MG, Brazil
[4] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
MEROZOITE SURFACE PROTEIN-1; VACCINE CANDIDATE MSP1(19); LCRV VIRULENCE PROTEIN; C-TERMINAL REGIONS; IMMUNE-RESPONSE; DENGUE VIRUS; IN-VIVO; TISSUE DISTRIBUTION; DEC-205; PROTEIN; FRAGMENT;
D O I
10.1038/srep39250
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
In vivo antigen targeting to dendritic cells (DCs) has been used as a way to improve immune responses. Targeting is accomplished with the use of monoclonal antibodies (mAbs) to receptors present on the DC surface fused with the antigen of interest. An anti-DEC205 mAb has been successfully used to target antigens to the DEC205(+) CD8 alpha(+) DC subset. The administration of low doses of the hybrid mAb together with DC maturation stimuli is able to activate specific T cells and induce production of high antibody titres for a number of different antigens. However, it is still not known if this approach would work with any fused protein. Here we genetically fused the alpha DEC205 mAb with two fragments (42-kDa and 19-kDa) derived from the similar to 200 kDa Plasmodium vivax merozoite surface protein 1 (MSP1), known as MSP1(42) and MSP1(19), respectively. The administration of two doses of alpha DEC-MSP1(42), but not of alpha DEC-MSP1(19) mAb, together with an adjuvant to two mouse strains induced high anti-MSP1(19) antibody titres that were dependent on CD4(+) T cells elicited by peptides present in the MSP1(33) sequence, indicating that the presence of T cell epitopes in antigens targeted to DEC205(+) DCs increases antibody responses.
引用
收藏
页数:15
相关论文
共 46 条
[1]   PROTEOLYTIC PROCESSING OF THE PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1 PRODUCES A MEMBRANE-BOUND FRAGMENT CONTAINING 2 EPIDERMAL GROWTH FACTOR-LIKE DOMAINS [J].
BLACKMAN, MJ ;
LING, IT ;
NICHOLLS, SC ;
HOLDER, AA .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1991, 49 (01) :29-34
[2]   USE OF A RECOMBINANT BACULOVIRUS PRODUCT TO MEASURE NATURALLY-ACQUIRED HUMAN-ANTIBODIES TO DISULFIDE-CONSTRAINED EPITOPES ON THE PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1 (MSP1) [J].
BLACKMAN, MJ ;
HOLDER, AA .
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 1993, 6 (04) :307-316
[3]   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].
BLACKMAN, MJ ;
HEIDRICH, HG ;
DONACHIE, S ;
MCBRIDE, JS ;
HOLDER, AA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (01) :379-382
[4]   Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance [J].
Bonifaz, L ;
Bonnyay, D ;
Mahnke, K ;
Rivera, M ;
Nussenzweig, MC ;
Steinman, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (12) :1627-1638
[5]   In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination [J].
Bonifaz, LC ;
Bonnyay, DP ;
Charalambous, A ;
Darguste, DI ;
Fujii, SI ;
Soares, H ;
Brimnes, MK ;
Moltedo, B ;
Moran, TM ;
Steinman, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (06) :815-824
[6]   Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses [J].
Boscardin, SB ;
Hafalla, JCR ;
Masilamani, RF ;
Kamphorst, AO ;
Zebroski, HA ;
Rai, U ;
Morrot, A ;
Zavala, F ;
Steinman, RM ;
Nussenzweig, RS ;
Nussenzweig, MC .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (03) :599-606
[7]   The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement [J].
Caminschi, Irina ;
Proietto, Anna I. ;
Ahmet, Fatma ;
Kitsoulis, Susie ;
Teh, Joo Shin ;
Lo, Jennifer C. Y. ;
Rizzitelli, Alexandra ;
Wu, Li ;
Vremec, David ;
van Dommelen, Serani L. H. ;
Campbell, Ian K. ;
Maraskovsky, Eugene ;
Braley, Hal ;
Davey, Gayle M. ;
Mottram, Patricia ;
De Velde, Nicholas van ;
Jensen, Kent ;
Lew, Andrew M. ;
Wright, Mark D. ;
Heath, William R. ;
Shortman, Ken ;
Lahoud, Mireille H. .
BLOOD, 2008, 112 (08) :3264-3273
[8]   Dendritic cell targeting of survivin protein in a xenogeneic form elicits strong CD4+ T cell immunity to mouse survivin [J].
Charalambous, Anna ;
Oks, Margarita ;
Nchinda, Godwin ;
Yamazaki, Sayuri ;
Steinman, Ralph M. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (12) :8410-8421
[9]   Comparison of the immunogenic properties of recombinant proteins representing the Plasmodium vivax vaccine candidate MSP119 expressed in distinct bacterial vectors [J].
Cunha, MG ;
Rodrigues, MM ;
Soares, IS .
VACCINE, 2001, 20 (3-4) :385-396
[10]  
DALY TM, 1995, J IMMUNOL, V155, P236