scholarly journals Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Benjamin J. Evert ◽  
Shuxiong Chen ◽  
Robyn McConville ◽  
Ryan W. J. Steel ◽  
Julie Healer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Severe Disease ◽  
Cell Epitope ◽  
High Yield ◽  
T Cell Epitope ◽  
Peptide Epitopes ◽  
Malaria Vaccines ◽  
Efficacious Vaccine

AbstractThe current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria. Here we developed a particulate malaria vaccine based on the same CSP epitopes but using biopolymer particles (BPs) as an antigen carrier system. Specific B- and T-cell epitope-coated BPs were assembled in vivo inside an engineered endotoxin-free mutant of Escherichia coli. A high-yield production process leading to ~27% BP vaccine weight over biomass was established. The epitope-coated BPs were purified and their composition, i.e., the polymer core and epitope identity, was confirmed. Epitope-coated BPs were used alongside soluble peptide epitopes and empty BPs to vaccinate sheep. Epitope-coated BPs showed enhanced immunogenicity by inducing anti-NANP antibody titre of EC50 > 150,000 that were at least 20 times higher than induced by the soluble peptides. We concluded that the additional T-cell epitope was not required as it did not enhance immunogenicity when compared with the B-cell epitope-coated BPs. Antibodies specifically bound to the surface of Plasmodium falciparum sporozoites and efficiently inhibited sporozoite motility and traversal of human hepatocytes. This study demonstrated the utility of biologically self-assembled epitope-coated BPs as an epitope carrier for inclusion in next-generation malaria vaccines.

scholarly journals Interleukin 10–Mediated Immunosuppression by a Variant CD4 T Cell Epitope of Plasmodium falciparum

Immunity ◽  
1999 ◽  
Vol 10 (6) ◽  
pp. 651-660 ◽  
Author(s):  
Magdalena Plebanski ◽  
Katie L Flanagan ◽  
Edwin A.M Lee ◽  
William H.H Reece ◽  
Keith Hart ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Cell Epitope ◽  
Interleukin 10 ◽  
Cd4 T Cell ◽  
T Cell Epitope

scholarly journals Induction of Polyomavirus-Specific CD8+T Lymphocytes by Distinct Dendritic Cell Subpopulations

2001 ◽  
Vol 75 (1) ◽  
pp. 544-547 ◽  
Author(s):  
Donald R. Drake ◽  
Mandy L. Shawver ◽  
Annette Hadley ◽  
Eric Butz ◽  
Charles Maliszewski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Cd8 T Lymphocytes ◽  
Cell Subpopulations ◽  
Antigen Presenting

ABSTRACT Dendritic cells are pivotal antigen-presenting cells for generating adaptive T-cell responses. Here, we show that dendritic cells belonging to either the myeloid-related or lymphoid-related subset are permissive for infection by mouse polyomavirus and, when loaded with a peptide corresponding to the immunodominant anti-polyomavirus CD8+T-cell epitope or infected by polyomavirus, are each capable of driving expansion of primary polyomavirus-specific CD8+ T-cell responses in vivo.

High-throughput sequence typing of T-cell epitope polymorphisms in Plasmodium falciparum circumsporozoite protein

2000 ◽  
Vol 106 (2) ◽  
pp. 273-282 ◽  
Author(s):  
Ali Alloueche ◽  
Henrique Silveira ◽  
David J. Conway ◽  
Kalifa Bojang ◽  
Tom Doherty ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
High Throughput ◽  
Cell Epitope ◽  
Circumsporozoite Protein ◽  
T Cell Epitope

Peptides containing a dominant T-cell epitope from red cell band 3 have in vivo immunomodulatory properties in NZB mice with autoimmune hemolytic anemia

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3800-3806 ◽  
Author(s):  
Chia-Rui Shen ◽  
Abdel-Rahman Youssef ◽  
Anne Devine ◽  
Laura Bowie ◽  
Andrew M. Hall ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Cell Epitope ◽  
Band 3 ◽  
T Cell Epitope ◽  
Helper Epitope

Abstract The major target of the pathogenic red blood cell (RBC) autoantibodies in New Zealand black (NZB) mice is the anion channel protein band 3, and CD4+ T cells from NZB mice respond to band 3. Here, we demonstrate that a band 3 peptide 861-875, which is the predominant sequence recognized by NZB T cells in vitro, bears a dominant helper epitope able to modulate the autoimmune hemolyic anemia in vivo. The development of RBC-bound autoantibodies and anemia was accelerated in NZB mice injected with peptide 861-874, which is relatively insoluble, and inhalation of the peptide primed T cells for both peptide 861-874 and band 3 responses. By contrast, inhalation of a soluble analog (Glu861, Lys875) of peptide 861-874 deviated the autoimmune response toward a T helper-2 (Th2) profile, with marked increases in the ratio of interleukin-4 to interferon-γ produced by splenic T cells responding in vitro to either peptide 861-874 or band 3. Moreover, in mice that had received such treatment, the proportion of RBC-bound immunoglobulin G (IgG) molecules that were of the Th2-associated IgG1 isotype was also increased, and anemia was less severe. It is concluded that NZB autoimmune hemolytic anemia is helper dependent and that nasal administration of different peptides containing the dominant T-cell epitope can have potentially detrimental or beneficial effects on the disease. (Blood. 2003; 102:3800-3806)

RESTRICTED T-CELL EPITOPE DIVERSITY IN THE CIRCUMSPOROZOITE PROTEIN FROM PLASMODIUM FALCIPARUM POPULATIONS PREVALENT IN IRAN

2007 ◽  
Vol 76 (6) ◽  
pp. 1046-1051 ◽  
Author(s):  
SEDIGHEH ZAKERI ◽  
GEORGES SNOUNOU ◽  
MEHDI AVAZALIPOOR ◽  
AKRAM ABOUEI MEHRIZI ◽  
NAVID DINPARAST DJADID
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Cell Epitope ◽  
Circumsporozoite Protein ◽  
T Cell Epitope

Initial Identification of a Mouse Human Factor IX-Specific CD8+ T-Cell Epitope.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5490-5490
Author(s):  
Brad E. Hoffman ◽  
Roland W. Herzog
Keyword(s):  
T Cells ◽  
T Cell ◽  
Catalytic Domain ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
Factor Ix ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Ifn Γ

Abstract A significant complication associated with treatment of inherited protein deficiencies, such as hemophilia B, by gene replacement therapy is the potential for the activation of transgene specific B and T cells to the therapeutic protein, coagulation factor IX (F.IX). In addition to the potential for inhibitor formation as a result of MHC class II antigen presentation (CD4+ T cell-dependent activation of B cells, which may also be observed in conventional protein-based therapy), gene expression may lead to MHC class I presentation of F.IX-derived peptides to CD8+ T cells. Upon in vivo gene transfer, such immune responses to may elicit a cytotoxic T lymphocyte (CTL) response capable of destroying target cells that express the F.IX transgene product. Therefore, to better understand the role of F.IX-specific CD8+ T-cell responses, it is essential that MHC I-restricted CD8 T-cell epitopes be identified. Here, we used a peptide library consisting of 82 individual 15-mer peptides overlapping by ten residues that spans the complete human F.IX (hF.IX) protein to preliminarily identify a specific immunodominate CD8+ T-cell epitope. The peptides were pooled into groups, each containing 8–11 peptides to create a matrix of 18 pools, with each peptide represented in two pools. C3H/HeJ were immunized with 5×1010 vector genomes of E1/E3-deleted adenovirus expressing hF.IX (Ad-hF.IX) via intramuscular injection into the quadriceps. Nine days later, the harvested spleen and popliteal lymph node cells were pooled and evaluated for CD8+ T-cell responses by intracellular cytokine staining for IFN-γ after being stimulated for 5h with peptides or controls. The frequency of IFN-γ producing hF.IX-specific CD8+ T-cells was determined by flow cytometry. While 16 pools from Ad-hF.IX immunized C3H/HeJ mice showed no response above the frequency of mock-stimulated cells, lymphocytes from two overlapping pools demonstrated a ~2.5-fold increase in frequency of CD8+ IFN-γ+ cells. From these results we can conclude that peptide 74 (SGGPHVTEVEGTSFL) contains a CD8+ T cell epitope for C3H/HeJ mice (H-2k haplotype). Furthermore, splenocytes from naive mice failed to respond to any of the peptide pools. The amino acid sequence corresponding to peptide 74 is located within the catalytic domain of hF.IX. This finding is of particular interest, in that, we previously reported a peptide containing the immunodominate CD4+ T-cell epitope in C3H/HeJ is also located within the catalytic domain of hF.IX (Blood 108:408). The definitive identification of hF.IX-specific CD8+ epitopes will facilitate the evaluation of experimental gene therapy strategies in murine models by providing a reagent for in vitro stimulation of F.IX specific CD8+ lymphocytes. For example, we can now determine the efficiency of CD8+ T cell activation as a function of vector, route, and dose following in vivo gene transfer.

Sign in / Sign up

Export Citation Format

Share Document