Linked Life Data

12213399

Source:http://linkedlifedata.com/resource/pubmed/id/12213399

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27-28
pubmed:dateCreated
2002-9-5
pubmed:abstractText
Three immunodominant leishmanial antigens (TSA, LmSTI1 and LeIF) previously identified in the context of host response to infection in infected donors and BALB/c mice, as well as their ability to elicit at least partial protection against Leishmania major infection in the BALB/c mouse model, were selected for inclusion into a subunit based vaccine. This is based on the premise that an effective vaccine against leishmaniasis (a complex parasitic infection) would require a multivalent cocktail of several antigens containing a broader range of protective epitopes that would cover a wide range of MHC types in a heterogeneous population. For practical considerations of vaccine development, we report on the generation of a single recombinant polyprotein comprising the sequences of all three open reading frames genetically linked in tandem. The resulting molecule, Leish-111f, comprises an open reading frame that codes for a 111kDa polypeptide. Evaluation of the immunogenicity and protective efficacy of Leish-111f formulated with IL-12 revealed that the immune responses to the individual components were maintained and as well, rLeish-111f protected BALB/c mice against L. major infection to a magnitude equal or superior to those seen with any of the individual components of the vaccine construct or SLA, a soluble Leishmania lysate. But because rIL-12 is expensive and difficult to manufacture and its efficacy and safety as an adjuvant for human use is questionable, we screened for other adjuvants that could potentially substitute for IL-12. We report that monophosphoryl lipid A (MPL) plus squalene (MPL-SE) formulated with rLeish-111f elicited protective immunity against L. major infection. The demonstrated feasibility to manufacture a single recombinant vaccine comprising multiple protective open reading frames and the potential use of MPL-SE as a substitute for IL-12, takes us closer to the realization of an affordable and safe Leishmania vaccine.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0264-410X
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3292-303
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12213399-Adjuvants, Immunologic, pubmed-meshheading:12213399-Amino Acid Sequence, pubmed-meshheading:12213399-Animals, pubmed-meshheading:12213399-Antibodies, Protozoan, pubmed-meshheading:12213399-Base Sequence, pubmed-meshheading:12213399-CD4-Positive T-Lymphocytes, pubmed-meshheading:12213399-DNA, Protozoan, pubmed-meshheading:12213399-Female, pubmed-meshheading:12213399-Humans, pubmed-meshheading:12213399-Leishmania major, pubmed-meshheading:12213399-Leishmaniasis, Cutaneous, pubmed-meshheading:12213399-Lipid A, pubmed-meshheading:12213399-Mice, pubmed-meshheading:12213399-Mice, Inbred BALB C, pubmed-meshheading:12213399-Molecular Sequence Data, pubmed-meshheading:12213399-Open Reading Frames, pubmed-meshheading:12213399-Protozoan Vaccines, pubmed-meshheading:12213399-Squalene, pubmed-meshheading:12213399-Vaccines, Synthetic
pubmed:year
2002
pubmed:articleTitle
Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant.
pubmed:affiliation
Corixa Corporation, 1124 Columbia Street, Suite 200, Seattle, WA 98104, USA. skeiky@corixa.com
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't