Development of two monoclonal antibodies against Plasmodium falciparum sporozoite surface protein 2 and mapping of B-cell epitopes
| Autor: | Joao C. Aguiar, L F Yuan, R. A. Houghten, E Andersen, Yupin Charoenvit, A Oloo, Benjamin Wizel, Giampietro Corradin, Manjit Kaur, P. De La Vega, Stephen L. Hoffman, John B. Sacci, Victoria Fallarme, William O. Rogers |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.drug_class
Molecular Sequence Data Plasmodium falciparum Immunology Protozoan Proteins Antibodies Protozoan Monoclonal antibody Microbiology Epitope Mice Antigen Malaria Vaccines parasitic diseases medicine Animals Amino Acid Sequence B-Lymphocytes Mice Inbred BALB C Vaccines Synthetic biology Malaria vaccine Antibodies Monoclonal biology.organism_classification Virology Mice Inbred C57BL Infectious Diseases Epitope mapping Polyclonal antibodies biology.protein Female Immunization Parasitology Epitope Mapping Plasmodium yoelii Research Article |
| Zdroj: | Infection and Immunity. 65:3430-3437 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.65.8.3430-3437.1997 |
| Popis: | The Plasmodium yoelii sporozoite surface protein 2 (PySSP2) is the target of protective cellular immunity. Cytotoxic T cells specific for the Plasmodium falciparum analog PfSSP2, also known as thrombospondin-related anonymous protein (TRAP), are induced in human volunteers immunized with irradiated sporozoites. PfSSP2 is an important candidate antigen for a multicomponent malaria vaccine. We generated and characterized three monoclonal antibodies (MAbs) specific for PfSSP2/TRAP. The MAbs PfSSP2.1 (immunoglobulin G1 [IgG1]), PfSSP2.2 (IgG2a), and PfSSP2.3 (IgM) were species specific and identified three distinct B-cell epitopes containing sequences DRYI, CHPSDGKC, and TRPHGR, respectively. PfSSP2.1 partially inhibited P. falciparum liver-stage parasite development in human hepatocyte cultures (42 and 86% in two experiments at 100 microg/ml). Mice immunized with vaccinia virus expressing full-length PfSSP2 protein produced antibodies to (DRYIPYSP)3, and humans living in malaria-endemic areas (Indonesia and Kenya), who have lifelong exposure and partial clinical immunity to malaria, had antibodies to both (DRYIPYSP)3 and (CHPSDGKCN)2. Mice immunized with multiple antigen peptides MAP4 (DRYIPYSP)3P2P30 and MAP4 (CHPSDGKCN)3P2P30 in TiterMax developed antibodies to sporozoites that partially inhibited sporozoite invasion of human hepatoma cells (39 to 71% at a serum dilution of 1:50 in three different experiments). The modest inhibitory activities of the MAbs and the polyclonal antibodies to PfSSP2/TRAP epitopes do not suggest that a single-component vaccine designed to induce antibodies against PfSSP2/TRAP will be protective. Nonetheless, the MAbs directed against PfSSP2, and the peptides recognized by these MAbs, will be essential reagents in the development of PfSSP2/TRAP as a component of a multivalent P. falciparum human malaria vaccine. |
| Databáze: | OpenAIRE |
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