Use of Double Aro Salmonella Mutants to Stably Express HPV16 E7 Protein Epitopes Carried by HBV Core Antigen
Attenuated Salmonella strains have been used as vectors for delivering antigens from other pathogens via the oral. route1. These organisms are particularly efficient in eliciting mucosal. responses as well as cellular and humoral. responses against the heterologous antigen. Among the characterised of these attenuated Salmonella strains are genetically engineered aro mutants which are defective in one more of the genes required for the synthesis of aromatic compounds, including para-aminobenzoic acid and aromatic amino acids2. S.typhimurium aroA, aroD double mutants have been used as carriers to deliver a variety of heterologous antigens to the mammalian immune system. Examples are the P.69 Pertactin antigen of Bordetella pertussis 3 and tetanus toxin fragment C. The nucleocapsid of the Hepatitis B Virus (HBV), also known as core antigen, is a complex polymer made up of approximately 180 copies of a single 21KDa polypeptide which spontaneously assemble together into 27 nm diameter particles5. In spite of being internal. viral. antigens, the particles are very powerful humoral. and cellular immunogens6. An important feature of the core particles is their ability to provide T helper determinants for B lymphocytes directed against epitopes of other molecules physically linked to them7,8. This carrier ability has been exploited for eliciting immune responses against peptide sequences from different viruses. Chimeric core particles with inserted heterologous epitopes from human rhino virus, HBV, HIV and murine cytomegalovirus have been successfully used to elicit B and T cell responses in mice (for a review see 9). The strongest antibody responses were obtained when insertions were made in an immunodominant region of the protein known as the el loop. This region is thought to be an exposed loop structure accessible to the immune system in the surface of the core particle10.
KeywordsBordetella Pertussis Core Antigen Human Rhino Virus Heterologous Antigen Immunodominant Region
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