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

¹ Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium
² School of Pharmaceutical Sciences, Kitasato University, Tokyo 108,
³ Jichi Medical School, Yakushiji, Minamikawachi, Tochigi 329-04
and⁴ Faculty of Agriculture, University of Gifu, Gifu 501-11, Japan

The immunomodulating and murine cytomegalovirus (MCMV)-inhibiting effects of the synthetic lipid A subunit analogue GLA-60 were investigated in different strains of immunodeficient mice. Peritoneal natural killer (NK) cells obtained from nude (nu/nu) C57BL/6 mice or normal NMRI mice, which had been treated intraperitoneally with 10 µg of GLA-60 1 day earlier, exhibited a greater cytolytic activity than those from untreated mice. GLA-60 also stimulated NK cell activity in SCID (severe combined immune deficiency) mice (which are T and B cell-defective), but not in NK cell-defective beige (C57BL/6 bg/bg) mice. GLA-60 also enhanced the phagocytic activity of peritoneal macrophages in beige, nude and NMRI mice, but not in SCID mice. GLA-60, when administered as a single 150 µg dose 1 day before infection, completely protected beige mice against MCMV-associated mortality. It also caused a significant increase in the life-span of MCMV-infected nude and SCID mice.

Received 14 January 1993; accepted 18 February 1993.

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