In:
Infection and Immunity, American Society for Microbiology, Vol. 70, No. 8 ( 2002-08), p. 4471-4476
Abstract:
Apical membrane antigen 1 (AMA-1) is a highly promising malaria blood-stage vaccine candidate that has induced protection in rodent and nonhuman primate models of malaria. Authentic conformation of the protein appears to be essential for the induction of parasite-inhibitory antibody responses. Here we have developed a synthetic gene with adapted codon usage to allow expression of Plasmodium falciparum FVO strain AMA-1 (PfAMA-1) in Pichia pastoris . In addition, potential N-glycosylation sites were changed, exploiting the lack of conservation of these sites in Plasmodium , to obtain high-level secretion of a homogeneous product, suitable for scale-up according to current good manufacturing procedures. Purified PfAMA-1 displayed authentic antigenic properties, indicating that the amino acid changes had no deleterious effect on the conformation of the protein. High-titer antibodies, raised in rabbits, reacted strongly with homologous and heterologous P. falciparum by immunofluorescence. In addition, purified immunoglobulin G from immunized animals strongly inhibited invasion of red blood cells by homologous and, to a somewhat lesser extent, heterologous P. falciparum .
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.70.8.4471-4476.2002
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2002
detail.hit.zdb_id:
1483247-1
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