SUPERIOR EFFICACY OF SECRETED OVER SOMATIC ANTIGEN DISPLAY IN RECOMBINANT SALMONELLA VACCINE-INDUCED PROTECTION AGAINST LISTERIOSIS

Vaccination provides the most potent measure against infectious diseas e, and recombinant (r) viable vaccines expressing defined pathogen-der ived antigens represent powerful candidates for future vaccination str ategies. In a new approach we constructed r-aroA(-) Salmonella typhimu rium displaying p60 or listeriolysin (Hly) antigen of listeria monocyt ogenes in secreted or somatic form in the host cell. Vaccination of mi ce with r-aroA(-) S. typhimurium induced protection against the intrac ellular pathogen L. monocytogenes only with secreted and not with soma tic antigen, Secreted Hly was slightly more potent in inducing protect ive immunity than secreted p60, Both r-aroA(-) S. typhimurium secretin g p60 in the endosome and r-aroA(-) S. typhimurium secreting Hly in th e cytosol induced protective CD4(+) and CD8(+) T-cells suggesting CD8( +) T-cell stimulation independent from intracellular residence of r-ar oA(-) S. typhimurium carriers. Hence, not only the type of antigen but also its display by the r-carrier within the host cell critically inf luences vaccine efficacy.