Immunogenicity of an engineered internal image antibody.

Abstract

We engineered an antibody expressing in the third complementarity-determining region of its heavy chain variable region a "foreign" epitope, the repetitive tetrapeptide Asn-Ala-Asn-Pro (NANP) of the circumsporozoite protein of Plasmodium falciparum parasite, one of the etiologic agents of malaria in humans. A monoclonal antibody to P. falciparum specific for the (NANP)n amino acid sequence bound to the engineered antibody, and a synthetic (NANP)3 peptide blocked this interaction. Immunization of rabbits and mice with the engineered antibody resulted in the elicitation of a humoral response to (NANP)3 synthetic peptide and P. falciparum parasite. In mice, in which immunity to the (NANP)n epitope is highly restricted by immune response genes, antibodies were induced in responder and nonresponder haplotypes of the major histocompatibility complex. Rabbit antibodies efficiently inhibited the in vitro invasion of cultured liver cells by P. falciparum parasite. Collectively, this study indicates that immunity to malaria in the absence of the parasite can be induced using antibody variable regions engineered to mimic the parasite's molecular structure. In general terms, the results suggest that antibody (idiotype) mimicry of an exogenous antigen is possible and may only require a discrete stretch of identity between the two molecules. The implication for the preparation of antibody-based vaccines and idiotype regulation of immunity are discussed.

• Authors: R Billetta, M R Hollingdale, M Zanetti
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 88 Issue 11 Pg. 4713-7 (Jun 01 1991) ISSN: 0027-8424 [Print] United States
• PMID: 1905014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antigens, Protozoan
• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region
• Oligonucleotide Probes
• Peptides
• Protozoan Proteins
• circumsporozoite protein, Protozoan

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Monoclonal (immunology)
• Antibody Formation
• Antigens, Protozoan (immunology)
• Base Sequence
• Genetic Engineering (methods)
• Immunoglobulin Heavy Chains (genetics, immunology)
• Immunoglobulin Variable Region (genetics, immunology)
• Malaria (immunology)
• Mice
• Mice, Inbred Strains
• Molecular Sequence Data
• Oligonucleotide Probes
• Peptides (chemical synthesis)
• Plasmodium falciparum (immunology)
• Protozoan Proteins