Pertussis is a disease of global significance, particularly affecting infants in the first year of life. Currently licensed pertussis vaccines are highly efficacious, but questions regarding their safety have led to public fears of vaccine related injuries. The proposed investigations examine the possibility of producing a subunit vaccine composed of pertussis antigens expressed in heterologous hosts by virtue of recombinant DNA methodology. In preliminary experiments, specific antigenic components of the bacterium believed capable of eliciting or augmenting protective immune responses against disease will be isolated. These components are: the S-1 subunit of the pertussis toxin, the 58,000-dalton subunit of the filamentous hemagglutinin, and each of three serotype-specific fimbrial agglutinogens. N-terminal amino acid sequences will be obtained for each polypeptide with a gas-phase microsequenator. A series of oligonucleotide probes representing predicted nucleotide sequences encoding each antigen will be synthesized and used as hybridization probes to isolate the genes for these proteins from B. pertussis genomic libraries. In later investigations, these genes will be installed in host-vector systems capable of high-level expression of heterologous proteins. The recombinant-derived proteins subsequently produced will be assessed for immunopotency in experimental animals.
| Burnette, W N; Cieplak, W; Mar, V L et al. (1988) Pertussis toxin S1 mutant with reduced enzyme activity and a conserved protective epitope. Science 242:72-4 |
| Cieplak, W; Burnette, W N; Mar, V L et al. (1988) Identification of a region in the S1 subunit of pertussis toxin that is required for enzymatic activity and that contributes to the formation of a neutralizing antigenic determinant. Proc Natl Acad Sci U S A 85:4667-71 |
