Artículos de revistas
Immunization With The Maebl M2 Domain Protects Against Lethal Plasmodium Yoelii Infection
Registro en:
Immunization With The Maebl M2 Domain Protects Against Lethal Plasmodium Yoelii Infection. Amer Soc Microbiology, v. 83, p. 3781-3792 OCT-2015.
0019-9567
WOS:000362492600003
10.1128/IAI.00262-15
Autor
Leite
Juliana A.; Bargieri
Daniel Y.; Carvalho
Bruna O.; Albrecht
Letusa; Lopes
Stefanie C. P.; Kayano
Ana Carolina A. V.; Farias
Alessandro S.; Chia
Wan Ni; Claser
Carla; Malleret
Benoit; Russell
Bruce; Castineiras
Catarina; Santos
Leonilda M. B.; Brocchi
Marcelo; Wunderlich
Gerhard; Soares
Irene S.; Rodrigues
Mauricio M.; Renia
Laurent; Costa
Fabio T. M.
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. 83 10
3781 3792 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Instituto Nacional de Ciencia e Tecnologia de Vacinas (INCTV) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) SIgN under the Agency for Science, Technology and Research (A*STAR, Singapore) Yong Loo Lin School of Medicine, National University of Singapore Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)