NDLI: Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection

Content Provider	PubMed Central
Author	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 Castiñeiras, Catarina Santos, Leonilda M. B. Brocchi, Marcelo Wunderlich, Gerhard Soares, Irene S. Rodrigues, Mauricio M. Rénia, Laurent Costa, Fabio T. M.
Editor	Adams, J. H.
Copyright Year	2015
Abstract	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.
Related Links	http://dx.doi.org/10.1128/iai.00262-15
Ending Page	3792
Page Count	12
Starting Page	3781
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	10
Volume Number	83
Language	English
Publisher	American Society for Microbiology
Publisher Date	2015-10-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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