Listeria monocytogenes vectors have shown promise for delivery of viral and tumor antigens in animals. We used two mutant vector strains deleted for actA/plcB (BMB72) and actA/inlB (BMB54), and engineered both strains to secrete a heterologous nucleoprotein antigen from the Influenza A virus. Strains were evaluated in vitro and in mice. Twenty-two healthy volunteers received single oral doses of either strain in a physiological study of safety, shedding, and immunogenicity. Volunteers were observed in the hospital for seven days and had daily blood cultures, routine safety blood tests (complete blood count with differential; hepatic and renal function), and fecal cultures; none had fever, positive blood cultures, prolonged shedding, or serious or unexpected events. Live attenuated bacteria expressing foreign antigens present a promising approach in the development of human immunotherapies and vaccines. Favorable attributes of Listeria monocytogenes include its innate immunostimulatory properties, efficient cytosolic entry of antigen presenting cells, and its ability to stimulate vigorous CD4 and CD8 T cell responses. L. monocytogenes antigen processing †Present address:
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