Protective activity of lipid A analogue GLA-60 against murine cytomegalovirus infection in mice.

Abstract

A chemically synthesized lipid A subunit analogue, GLA-60 (2-deoxy-4-O-phosphono-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R) - 3-tetradecanoyloxytetradecanoyl]-D-glucose), has many of the activities of endotoxins but little, if any, toxicity. We investigated the protective activity of GLA-60 against murine cytomegalovirus (MCMV) infection in NMRI mice. Intraperitoneal administration of GLA-60 at 1 day before MCMV infection at doses of 1, 10, or 100 micrograms per mouse significantly reduced mortality. GLA-60 stimulated peritoneal natural killer (NK) cell and macrophage activities, and these activities were abolished by in vitro treatment with anti-asialo GM1 antibody and anti-Mac1 antibody, respectively. GLA-60 proved also protective against MCMV infection in mice in which either NK cells or macrophages were depleted by in vivo treatment with anti-asialo GM1 or anti-Mac1 antibody. The anti-MCMV activity of GLA-60 can at least be partially attributed to activation of NK cells and macrophages.