T-cell activation and cytokine production via a bispecific single-chain antibody fragment targeted to blood-stage malaria parasites

Yoshida, Shigeto; Kobayashi, Tominari; Matsuoka, Hiroyuki; Seki, Chisato; Gosnell, William L.; Chang, Sandra P.; Ishii, Akira

doi:10.1182/blood-2002-03-0831

Cited by 20 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A novel bispecific Ab has recently been developed for the treatment of P falciparum. 45 This reagent targeted the CD3 antigen of human T cells to MSP1 19 . In cooperation with T cells, the bispecific Ab induced a significant increase in merozoite phagocytosis and growth inhibition of P falciparum in vitro.…”

Section: Discussionmentioning

confidence: 99%

Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection

Pleass

Ogun

McGuinness

et al. 2003

Blood

View full text Add to dashboard Cite

Parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. The success of passive immunization suggests that immunoglobulin (Ig)-based therapies are effective. To further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric IgG1 IntroductionMalaria continues to kill approximately 2 million people each year. 1 The success of passive immunization in humans and animals suggests that immunoglobulin (Ig)-based therapies could be effective. 2,3 Manipulating antibody (Ab) genes allows the design of Ig with defined class and specificity, targeting protective epitopes on the parasite surface. An appropriate target is the 19-kDa C-terminal region of merozoite surface protein 1 (MSP1 19 ). This polypeptide displays limited sequence polymorphism, 4 is expressed by all vertebrate life-cycle stages, 5 and acts as a major target of the erythrocyte invasion-inhibitory Ab response in individuals immune to Plasmodium falciparum malaria. 6 The mechanisms whereby Ig mediates protective immunity in malaria remain unclear. 7 A primary role of Ab appears to involve blocking of merozoite invasion of erythrocytes. 8 However, studies using human Ab suggest that the protective effects are mediated through interaction with specific receptors for the Ig Fc region (FcR) expressed on various effector cells. 9,10 Using Plasmodium yoelii in a murine model to address these possibilities, we generated human chimeric IgG1 and IgA1 Abs recognizing an epitope on P yoelii MSP1 19 . We have investigated the potential of these intact Abs, and a novel diabody with specificity for both MSP1 19 and a human receptor for IgG Fc, Fc␥RI, as novel malaria therapeutics. Materials and methods Construction of expression vectorsVariable heavy (VH) and light (VL) complementary DNAs (cDNAs) were cloned from mouse hybridomas B10 (anti-MSP1 19 ) and M22 (anti-human Fc␥RI) by reverse transcriptase-polymerase chain reaction (RT-PCR) using degenerate primers (5Ј-SARGTNMARCTGCAGSAGTC-3Ј and 5Ј-TGAGGAGACGGTGACCGTGGTYCCTTGGCCCC-3Ј for VH and 5Ј-GAYATTGAGCTCACMCARWCTMCA-3Ј and 5Ј-CCGTTTBAKCTC-GAGCTTKGTSCC-3Ј for VL). 11,12 An alternative primer incorporating a BssHII restriction enzyme site was used to reamplify B10 VH to facilitate subcloning. The IgA1 heavy-chain constant region was subcloned as a BamHI-SalI fragment from an ␣ chain gene-containing plasmid 13 into pAD-Gal4-2.1 (Stratagene, La Jolla, CA) and then as a BamHI-XbaI fragment into pVHExpress (a kind gift from Andrew Bradbury, Los Alamos National Laboratory, Los Alamos, NM), 14 replacing the ␥1 constant domains to yield pVHExpress ␣1H. The VH genes were inserted into pVHExpress and pVHExpress ␣1H, upstream of the ␥1 or ␣1 constant regions, respectively, and the VL genes into pVKExpress upstream of the human gene. 14 To generate the Fc␥RI x MSP1 19 diabody, an overlapping PCR-based strategy was used. First, the VH and VL regions of B10 and M22 were amplified. The 5Ј VH primers inco...

show abstract

Section: Discussionmentioning

confidence: 99%

Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection

Pleass

Ogun

McGuinness

et al. 2003

Blood

View full text Add to dashboard Cite

show abstract

“…rAAPP and rTrx were produced and solubilized under denaturing conditions using 6 M guanidine-HCl, and then purified by affinity chromatography on a Ni-NTA column (Qiagen, Valencia, CA) followed by dialysis against PBS as described previously. 17 The purity of the recombinant proteins was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the protein yield was estimated by comparison with BSA standards. …”

mentioning

confidence: 99%

Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito

Yoshida

Sudo

Niimi

et al. 2008

Blood

Self Cite

View full text Add to dashboard Cite

During blood feeding, mosquitoes inject saliva containing a mixture of molecules that inactivate or inhibit various components of the hemostatic response to the bite injury as well as the inflammatory reactions produced by the bite, to facilitate the ingestion of blood. However, the molecular functions of the individual saliva components remain largely unknown. Here, we describe anopheline antiplatelet protein (AAPP) isolated from the saliva of Anopheles stephensi, a human malaria vector mosquito. AAPP exhibited a strong and specific inhibitory activity toward collagen-induced platelet aggregation. The inhibitory mechanism involves direct binding of AAPP to collagen, which blocks platelet adhesion to collagen and inhibits the subsequent increase in intracellular Ca(2+) concentration ([Ca(2+)]i). The binding of AAPP to collagen effectively blocked platelet adhesion via glycoprotein VI (GPVI) and integrin alpha(2)beta(1). Cell adhesion assay showed that AAPP inhibited the binding of GPVI to collagen type I and III without direct effect on GPVI. Moreover, intravenously administered recombinant AAPP strongly inhibited collagen-induced platelet aggregation ex vivo in rats. In summary, AAPP is a malaria vector mosquito-derived specific antagonist of receptors that mediate the adhesion of platelets to collagen. Our study may provide important insights for elucidating the effects of mosquito blood feeding against host hemostasis.

show abstract

“…This includes bispecific antibodies (BsAbs) that were developed to recognise both P. yoelii MSP1 and human FcγR1 [9]. Another bispecific scFv combination, linked by a flexible peptide linker (Gly4-Ser)3, has been developed to target P. falciparum bloodstage malaria parasites, by linking CD3 antigen of human T-cells and MSP1 [123]. Even a trispecific antibody has been developed in the malaria field, as previously involved in cancer treatment development, to link two potential targets of malaria (merozoite surface protein 1 Previous studies have acknowledged the fact that upon exposure to a new malaria infection, parasite-specific antibody levels rise noticeably within 1-2 weeks [89,90].…”

Section: Anti-malarial Antibodiesmentioning

confidence: 99%

Control of Malaria by Bio-Therapeutics and Drug Delivery Systems

et al. 2017

View full text Add to dashboard Cite

T-cell activation and cytokine production via a bispecific single-chain antibody fragment targeted to blood-stage malaria parasites

Cited by 20 publications

References 29 publications

Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection

Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection

Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito

Control of Malaria by Bio-Therapeutics and Drug Delivery Systems

Contact Info

Product

Resources

About