Killed Listeria monocytogenes vaccine becomes protective on addition of polyanions

Abstract

IN the interaction between macrophages and intracellular parasites, microbial components which prevent phagosome–lysosome fusion^1,2 have a decisive role. The resistance to faculative intracellular parasite Listeria monocytogenes is a form of cell-mediated immunity³, as it can be passively transferred with viable lymphoid cells⁴. Resistance to listeria infection can be induced by sublethal numbers of viable listeria^5,6. Induction of resistance by non-viable listeria, however, is effective only after repeated injections of listeria preparations in combination with lipopolysaccharides⁷. Lipopolysaccharide is cytotoxic against macro-phages^8,9, suggesting that the difference in processing of viable and dead microorganisms by macrophages might explain the induction of resistance by vaccine of live and not of dead bacteria. Impairing macrophage activity might result in a processing of dead listeria advantageous for the induction of resistance. We show here that killed L. monocytogenes vaccine becomes protective when the polyanions dextran sulphate (DS 500, molecular weight 500,000, Serva) and suramin (Bayer) are added. These polyanions are known to inhibit phagosome–lysosome fusion in macrophages^2,10. Moreover, dextran sulphate is a potent adjuvant for both humoral¹¹ and cell-mediated responses¹². The latter might be particularly important in view of the requirement of cell-mediated immunity for resistance to listeria³.