Linked Life Data

11812154

Source:http://linkedlifedata.com/resource/pubmed/id/11812154

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-1-28
pubmed:abstractText
The yellow fever 17D virus (YF17D) has several characteristics that are desirable for the development of new, live attenuated vaccines. We approached its development as a vector for heterologous antigens by studying the expression of a humoral epitope at the surface of the E protein based on the results of modelling its three-dimensional structure. This model indicated that the most promising insertion site is between beta-strands f and g, a site that is exposed at the external surface of the virus. The large deletion of six residues from the fg loop of the E protein from yellow fever virus, compared to tick-born encephalitis virus, leaves space at the dimer interface for a large insertion without creating steric hindrance. We have tested this hypothesis by inserting a model humoral epitope from the circumsporozoite protein of Plasmodium falciparum consisting of triple NANP repeats. Recombinant virus (17D/8) expressing this insertion flanked by two glycine residues at each end, is specifically neutralized by a monoclonal antibody to the model epitope. Furthermore, mouse antibodies raised to the recombinant virus recognize the parasite protein in an ELISA assay. Serial passage analysis confirmed the genetic stability of the insertion made in the viral genome and the resulting 17D/8 virus is significantly more attenuated in mouse neurovirulence tests than the 17DD vaccine. The fg loop belongs to the dimerization domain of the E protein and lies at the interface between monomers. This domain undergoes a low pH transition, which is related to the fusion of the viral envelope to the endosome membrane. It is conceivable that a slower rate of fusion, resulting from the insertion close to the dimer interface, may delay the onset of virus production and thereby lead to a milder infection of the host. This would account for the more attenuated phenotype of the recombinant virus in the mouse model and lower extent of replication in cultured cells. The vectorial capacity of the yellow fever virus is being further explored for the expression and presentation of other epitopes, including those mediating T-cell responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Academic Press.
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
315
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
873-85
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11812154-Amino Acid Sequence, pubmed-meshheading:11812154-Animals, pubmed-meshheading:11812154-Antibodies, Monoclonal, pubmed-meshheading:11812154-Antigens, Protozoan, pubmed-meshheading:11812154-Cell Line, pubmed-meshheading:11812154-Epitopes, B-Lymphocyte, pubmed-meshheading:11812154-Gene Expression, pubmed-meshheading:11812154-Genome, Viral, pubmed-meshheading:11812154-Hydrogen-Ion Concentration, pubmed-meshheading:11812154-Immunodominant Epitopes, pubmed-meshheading:11812154-Malaria, pubmed-meshheading:11812154-Malaria Vaccines, pubmed-meshheading:11812154-Mice, pubmed-meshheading:11812154-Models, Molecular, pubmed-meshheading:11812154-Molecular Sequence Data, pubmed-meshheading:11812154-Neutralization Tests, pubmed-meshheading:11812154-Plasmodium falciparum, pubmed-meshheading:11812154-Protein Structure, Tertiary, pubmed-meshheading:11812154-Sequence Alignment, pubmed-meshheading:11812154-Serial Passage, pubmed-meshheading:11812154-Survival Rate, pubmed-meshheading:11812154-Vaccines, Attenuated, pubmed-meshheading:11812154-Vaccines, Synthetic, pubmed-meshheading:11812154-Viral Envelope Proteins, pubmed-meshheading:11812154-Yellow fever virus
pubmed:year
2002
pubmed:articleTitle
Surface expression of an immunodominant malaria protein B cell epitope by yellow fever virus.
pubmed:affiliation
Departamento de Bioquímica e Biologia Molecular, Fundação Oswaldo Cruz Instituto Oswaldo Cruz, Rio de Janeiro, RJ 21045-900, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't