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.

• Authors: S Ikeda, J Neyts, M Matsuura, M Kiso, A Hasegawa, C Nishimura, E De Clercq
• Journal: Journal of medical virology (J Med Virol) Vol. 40 Issue 3 Pg. 222-7 (Jul 1993) ISSN: 0146-6615 [Print] United States
• PMID: 8394873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Lipid A
• Macrophage-1 Antigen
• GLA 60
• G(M1) Ganglioside
• asialo GM1 ganglioside

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Cytomegalovirus Infections (prevention & control)
• Female
• G(M1) Ganglioside (antagonists & inhibitors)
• Injections, Intraperitoneal
• Killer Cells, Natural (drug effects, immunology)
• Lipid A (administration & dosage, analogs & derivatives, pharmacology)
• Macrophage Activation (drug effects)
• Macrophage-1 Antigen
• Mice
• Phagocytosis (drug effects)