Immunological properties of foreign peptides in multiple display on a filamentous bacteriophage.
The genome of bacteriophage fd has been engineered to permit construction of hybrid virus particles in which the wild-type major coat protein (gpVIII) subunits were interspersed with coat proteins displaying one or other of two foreign peptides (fdMAL1, sequence NANPNANPNANP or fdMAL2, sequence NDDSYIPSAEKI) in the exposed N-terminal segments [Greenwood et al., J. Mol. Biol. 220 (1991) 821-827]. These sequences represent major antigenic determinants of the circumsporozoite protein of the malaria parasite, Plasmodium falciparum. The peptide epitopes in the hybrid bacteriophages were found to be strongly immunogenic in four different strains of mice without the use of external adjuvants, and the antibodies (Ab) were highly specific to the individual epitopes in ELISA assays. When tested in nude (nu/nu) and heterozygote (nu +/-) BALB/c mice, the immune response was found to be T-cell dependent and to undergo class-switching from IgM to IgG. Proliferation assays of T-cells taken from lymph nodes of BALB/c mice injected with bacteriophage particles in the presence or absence of Freund's complete adjuvant indicated no difference in the immune response. This way of generating Ab against peptide epitopes is simpler and much less expensive than the conventional method of peptide synthesis and coupling to a carrier protein for injection. The specificity of the immune response, the ability to recruit helper T-cells and the lack of need for external adjuvants suggest that it will also be an inexpensive and simple route to the production of effective vaccines.
Willis
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AE
Department of Biochemistry, University of Cambridge, UK.
Perham
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RN
Wraith
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D
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D002213:Capsid / Q000096:biosynthesis; D003001:Cloning, Molecular / Q000379:methods; D003090:Coliphages / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000906:Antibodies; D000939:Epitopes; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan