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Paper Information

Title: 

NEW APPROACHES FOR VACCINE DEVELOPMENT BASED ON GENETICALLY MODIFIED PARASITES AND VIRAL PEPTIDES: BIOSAFETY CONSIDERATIONS

Type: PAPER
Author(s): HAGHPARAST A.R.*,HENSEN E.J.,JANSE C.J.,WATERS A.P.
 
 *IMMUNOLOGY SECTION, DEPARTMENT OF PATHOBIOLOGY, FACULTY OF VETERINARY MEDICINE, FERDOWSI UNIVERSITY OF MASHHAD, IRAN
 
Name of Seminar: NATIONAL CONGRESS OF BIOTECHNOLOGY OF IRAN
Type of Seminar:  CONGRESS
Sponsor:  IRANIAN BIOTECHNOLOGY ASSOCIATION
Date:  2005Volume 4
 
 
Abstract: 

Infectious diseases continue to be a global health problem and are the cause of tremendous morbidity and mortality every year. Attempts to create an effective and protective vaccine have been a high global health priority. New generation of vaccines using modern cellular and molecular technology has helped to create the valuable tools to combat such health problems. However such a development in knowledge and technology has created numerous concerns and criticism over their biosafety aspects. This paper is based on the studies that were conducted in two different models of vaccine developments; the generation of genetically engineered plasmodium that are growth impaired as a means to create live attenuated parasites and evaluation of peptide vaccine against foot and mouth disease virus (FMDV).
Identification of elements and components that are necessary for virulence and try to eliminate them from the genome is a step towards developing attenuated live parasite as vaccine. Cell division and proliferation during parasite invasion are prerequisites factors for virulence. Eukaryotic elongation factor 1A (eEF1A) plays a central role in protein synthesis, cell growth and morphology. Malaria parasite possesses two identical genes encoding eEF1A (eef1aa and eef1ab). Using pbeef1
`a Plasmodium berghei mutants that lack an eEF1a gene, we demonstrate that the level of eEF1A production affects the proliferation of blood stages and parasite fitness. Pbeef1`a parasites can complete the vertebrate and mosquito phases of the life cycle, but the growth phase of the asexual blood stages is extended by up to 20%. Insight into protein synthesis and its influence on cell proliferation in malaria parasites might be used for drug discovery as well as generating slow growing parasites to study immunological intervention strategies involved in host-parasite interactions. Further attenuation of parasites through elongation of the cell cycle by affecting protein synthesis machinery might be used for testing the feasibility of the creation of attenuated live parasites as vaccine.
Antigenic peptides play a crucial role in the initiation of cell-mediated immune responses and may therefore be successfully used in antiviral vaccination strategies. The ability to elicit T and B cell responses after immunisation with peptide vaccine has considerable interest in developing viral vaccines intended to induce protective immunity. Foot and mouth disease virus (FMDV) is the cause of a highly contagious and economically devastating disease of cloven-hoofed livestock. Synthetic peptides derived from the major antigenic B cell site of VP1 of the virus have been shown to induce neutralising antibodies in a variety of species. Although guinea pigs can be readily protected against homotypic virus challenge after immunisation with VP1 [141-160], similar studies in outbreed population like cattle have not been successful and have directed research towards the identifications of T-cell epitopes and the restrictions imposed by MHC polymorphism. We used two different peptide vaccine compounds in a vaccination-challenge experiment in cattle. The protective capacity of a carrier coupled B cell epitope of FMDV, namely VP1 [141-156] was compared; when a defined T cell epitope like VP4 [20-34] was added as free peptide to this strong B cell epitope. The cellular and humoral immune responses of the animals were monitored during the experiment and the mechanisms behind the protection were speculated.

 
Keyword(s): PEPTIDE VACCINE, FOOT AND MOUTH DISEASE VIRUS, GENETICALLY MODIFIED PARASITES, PLASMODIUM BERGHEI
 
 
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