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Protection of OK-432, a Streptococcus pyogenes preparation, against lethal infection of mice with herpes simplex
1Research Laboratories, Chugai Pharmaceutical Co., Ltd., Tokyo.
Abstract:
We have studied the protective effect of OK-432, a biological response modifier (BRM) of Streptococcus pyogenes origin, on the lethal infection of mice with herpes simplex virus (HSV)-1. A single intraperitoneal (i.p.) injection of more than 10 micrograms of OK-432, when given at least two days before the infection, gave a marked effect yielding nearly 100% protection against ordinarily lethal infection. The protection was independent of the amount of infected virus inoculated. When given after the infection, the agent even at the maximal dose (100 micrograms), produced only a marginal effect. A single i.p. administration of OK-432 augmented the natural killer (NK) activity of peritoneal exudate cells and spleen mononuclear cells in mice 2 to 3 days after injection of OK-432, coinciding with the times when it induced a survival effect on HSV-infection. Treating OK-432-treated mice with a combination of an anti-macrophage agent, silica, and an anti-NK cell agent, anti-asialo GM1 serum, before infection diminished the antiviral effect of OK-432. The OK-432 protection against HSV infection was also markedly diminished in athymic nude mice. Thus, the protective effect of OK-432 on lethal HSV infection seems to be based on the activation of NK cells, macrophages, and T lymphocytes.
Insights
OK-432, a biological response modifier, provides nearly 100% protection against lethal herpes simplex virus (HSV) infection in mice when administered before exposure. This antiviral effect relies on activating natural killer (NK) cells, macrophages, and T lymphocytes.
Area of Science:
- Immunology
- Virology
- Microbiology
Background:
- Herpes simplex virus (HSV) causes lethal infections.
- Biological response modifiers (BRMs) can modulate the immune system.
- OK-432 is a BRM derived from Streptococcus pyogenes.
Purpose of the Study:
- To investigate the protective effect of OK-432 against lethal HSV-1 infection in mice.
- To elucidate the immunological mechanisms underlying OK-432's antiviral activity.
Main Methods:
- Mice were infected with HSV-1 and treated with varying doses of OK-432.
- Natural killer (NK) cell activity and macrophage function were assessed.
- The role of immune cells was evaluated using specific blocking agents (silica, anti-asialo GM1 serum) and athymic nude mice.
Main Results:
- A single intraperitoneal injection of OK-432 (≥10 µg) at least two days before HSV infection resulted in nearly 100% protection.
- The protective effect was observed regardless of the viral inoculum dose.
- OK-432 administration augmented NK cell activity and peritoneal exudate cells 2-3 days post-injection.
- Depletion of macrophages and NK cells, or the use of athymic nude mice, significantly reduced OK-432's protective effect.
Conclusions:
- OK-432 demonstrates significant protective efficacy against lethal HSV infection in mice.
- The antiviral effect of OK-432 is mediated by the activation of innate and adaptive immune cells, including NK cells, macrophages, and T lymphocytes.