Plasmodium vivax recombinant vaccine candidate AMA-1 plays an important role in adaptive immune response eliciting differentiation of dendritic cells


Autoria(s): BUENO, Lilian Lacerda; MORAIS, Cristiane Guimaraes; SOARES, Irene da Silva; BOUILLET, Leoneide Erica Maduro; BRUNA-ROMERO, Oscar; FONTES, Cor Jesus; FUJIWARA, Ricardo Toshio; BRAGA, Erika Martins
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2009

Resumo

The Apical Membrane Antigen-1 (AMA-1) is a well-characterized and functionally important merozoite protein and is currently considered a major candidate antigen for a malaria vaccine. Previously, we showed that AMA-1 has an influence on cellular immune responses of malaria-naive subjects, resulting in an alternative activation of monocyte-derived dendritic cells and induction of a pro-inflammatory response by stimulated PBMCs. Although there is evidence, from human and animal malaria model systems that cell-mediated immunity may contribute to both protection and pathogenesis, the knowledge on cellular immune responses in vivax malaria and the factors that may regulate this immunity are poorly understood. In the current work, we describe the maturation of monocyte-derived dendritic cells of P. vivax naturally infected individuals and the effect of P. vivax vaccine candidate Pv-AMA-1 on the immune responses of the same donors. We show that malaria-infected subjects present modulation of DC maturation, demonstrated by a significant decrease in expression of antigen-presenting molecules (CD1a, HLA-ABC and HLA-DR), accessory molecules (CD40, CD80 and CD86) and Fc gamma RI (CD64) receptor (P <= 0.05). Furthermore, Pv-AMA-1 elicits an upregulation of CD1a and HLA-DR molecules on the surface of monocyte-derived dendritic cells (P=0.0356 and P=0.0196, respectively), and it is presented by AMA-1-stimulated DCs. A significant pro-inflammatory response elicited by Pv-AMA-1-pulsed PBMCs is also demonstrated, as determined by significant production of TNF-alpha, IL-12p40 and IFN-gamma (P <= 0.05). Our results suggest that Pv-AMA-1 may partially revert DC down-modulation observed in infected subjects, and exert an important role in the initiation of pro-inflammatory immunity that might contribute substantially to protection. (c) 2009 Elsevier Ltd. All rights reserved.

Fundacao de Amparo a Pesquisa do Estado de Minas Gerais/FAPEMIG[CBB APQ-0997-4.01/07]

CAPES/Brazil

Brazilian National Research Council (CNPq)

Identificador

VACCINE, v.27, n.41, p.5581-5588, 2009

0264-410X

http://producao.usp.br/handle/BDPI/19604

10.1016/j.vaccine.2009.07.031

http://dx.doi.org/10.1016/j.vaccine.2009.07.031

Idioma(s)

eng

Publicador

ELSEVIER SCI LTD

Relação

Vaccine

Direitos

restrictedAccess

Copyright ELSEVIER SCI LTD

Palavras-Chave #Plasmodium vivax #AMA-1 #Dendritic cells #Pro-inflammatory response #Recombinant protein #Modulation #APICAL MEMBRANE ANTIGEN #FALCIPARUM-INFECTED ERYTHROCYTES #NECROSIS-FACTOR-ALPHA #BLOOD-STAGE MALARIA #IFN-GAMMA #IN-VITRO #ESCHERICHIA-COLI #RED-CELLS #MATURATION #ANTIBODIES #Immunology #Medicine, Research & Experimental
Tipo

article

original article

publishedVersion