YERSINIA PESTIS F1 GENETIC VACCINE IN COMBINATION WITH RECOMBINANT F1 PROTEIN PROMOTES BOTH CELLULAR AND ANTIBODY-MEDIATED IMMUNITY

Abstract

Genetic or DNA vaccines which involve the introduction of non-infectious nucleic acids in plasmids have attracted significant attention for future use in humans. A genetic vaccine for the bacterial disease caused by Yersinia pestis was examined. For comparative purposes, studies were also done with Clostridium tetanii DNA immunizations. The role of cellular immunity in resistance to infection by Yersinia is not well established. The enteropathogenic bacteria Y. pseudotuberculosis and Y. enterocolitica actively deliver antigens to the cytosol of eucaryotic cells, suggesting that cytotoxic T-lymphocyte (CTL) immunity may be induced by these species. In contrast Y. pestis lacks the outer membrane protein invasin that is necessary for attachment to cells and translocation of virulence factors into the cytosol. A genetic vaccine was used to induce intracellular expression of the fraction 1 (F1) capsular protein of Y. pestis within host mammalian cells and the ensuing immune response was examined. The F1 genetic vaccine stimulated more vigorous CTL responses than recombinant F1 polypeptide in BALB/c mice, suggesting the importance of cytosolic delivery for T-cell immunity to Y. pest/s. In addition, dominant T-helper 1 (TH1)-like antibody responses to plasm id-expressed F1 were observed in inbred strains of mice tested, whereas no antibody response occurred in outbred mice. These results suggest that the noninvasive nature of Y. pestis may provide an advantage for escaping host immune responses during the primary phase of infection. A priming immunization with the F1 genetic vaccine followed by a boost with recombinant F1 polypeptide produced a vigorous T-helper 2 (TH2)-like antibody response that was equivalent to 3 injections of F1 polypeptide. An immunization strategy based on a combination of recombinant protein and genetic vaccine may optimally promote both cellular and antibody-mediated immunity against Y. pestis.