Immunization with the MAEBL M2 domain protects against lethal Plasmodium yoelii infection
| Autor: | Ana Carolina A. V. Kayano, Fabio T. M. Costa, Catarina Castiñeiras, Irene da Silva Soares, Juliana A. Leite, Carla Claser, Benoit Malleret, Stefanie C. P. Lopes, Bruce Russell, Gerhard Wunderlich, Bruna O. Carvalho, Marcelo Brocchi, Alessandro S. Farias, Leonilda M.B. Santos, Daniel Y. Bargieri, Letusa Albrecht, Mauricio M. Rodrigues, Wan Ni Chia, Laurent Rénia |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Erythrocytes Immunology Protozoan Proteins Antibodies Protozoan Parasitemia Microbiology Mice Antigen parasitic diseases Malaria Vaccines medicine Animals Humans Apical membrane antigen 1 MALÁRIA Antiserum biology Merozoites Plasmodium yoelii biology.organism_classification medicine.disease Virology Malaria Protein Structure Tertiary Mice Inbred C57BL Infectious Diseases Ectodomain Sporozoites Microbial Immunity and Vaccines biology.protein Female Immunization Parasitology Antibody CD8 |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. MAEBL is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the Duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (AMA1) antigens. Although MAEBL does not appear to be essential for the survival of blood-stage forms, ectodomains M1 and M2, homologous to AMA1, seem to be involved in parasite attachment to erythrocytes, especially M2. MAEBL is necessary for sporozoite infection of mosquito salivary glands and is expressed in liver stages. Here, the Plasmodium yoelii MAEBL-M2 domain was expressed in a prokaryotic vector. C57BL/6J mice were immunized with doses of P. yoelii recombinant protein rPyM2-MAEBL. High levels of antibodies, with balanced IgG1 and IgG2c subclasses, were achieved. rPyM2-MAEBL antisera were capable of recognizing the native antigen. Anti-MAEBL antibodies recognized different MAEBL fragments expressed in CHO cells, showing stronger IgM and IgG responses to the M2 domain and repeat region, respectively. After a challenge with P. yoelii YM (lethal strain)-infected erythrocytes (IE), up to 90% of the immunized animals survived and a reduction of parasitemia was observed. Moreover, splenocytes harvested from immunized animals proliferated in a dose-dependent manner in the presence of rPyM2-MAEBL. Protection was highly dependent on CD4 + , but not CD8 + , T cells toward Th1. rPyM2-MAEBL antisera were also able to significantly inhibit parasite development, as observed in ex vivo P. yoelii erythrocyte invasion assays. Collectively, these findings support the use of MAEBL as a vaccine candidate and open perspectives to understand the mechanisms involved in protection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|