Protein engineering to create biologically active peptides: recombinant human rhinoviruses that display peptide sequences.
This paper describes the use of human rhinovirus to display peptides corresponding to biologically active sequences. While this system can be used to reconstruct essentially any biologically active sequence for which there is a corresponding ligand that can be used for its selection, we have focused on using this system to display immunogens from dangerous pathogens as a means to develop vaccines. Five mutagenesis approaches are illustrated as ways to generate functionally active moieties. The mutagenesis approaches illustrated can be employed with any of a large number of possible display vectors; however, human rhinovirus might be especially useful in cases where it will be important to derive the benefits of delivery by a live-virus approach. Examples are shown in which reconstruction of immunogens corresponding to the V3 loop of the gp120 glycoprotein of the human immunodeficiency virus type 1 (HIV-1) on the surface of rhinovirus has yielded apparently effective mimics of the HIV-1 immunogens (as measured by their ability to be neutralized by anti-HIV-1 antibodies as well as their ability to elicit the production of antibodies capable of neutralizing HIV-1 in cell culture). This system offers the opportunity to reconstruct functionally important moieties that derive from proteins or pathogens that are either too dangerous or difficult to isolate for use as vaccine preparations themselves.
Smith
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Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA.
Arnold
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E
Arnold
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D000595:Amino Acid Sequence; D000917:Antibody Formation; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D003062:Codon; D005822:Genetic Vectors; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D015202:Protein Engineering; D012229:Rhinovirus / Q000276:immunology*; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
D000956:Antigens, Viral; D003062:Codon; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic; D014765:Viral Vaccines