Cyclophosphamide and dimethyl dioctadecyl ammonium bromide immunopotentiate the delayed-type hypersensitivity response to inactivated enveloped viruses.

Immunization of BALB/c mice with measles virus inactivated with beta-propiolactone and mixed with 100 micrograms of the cationic surface-active lipid dimethyl dioctadecyl ammonium bromide (DDA) primes for a strong virus-specific delayed-type hypersensitivity (DTH) response that peaks 1 week later. Optimal immunization and challenge doses were found to be 8 and 4 micrograms/mouse, respectively, and pretreatment with 200 mg of cyclophosphamide/kg 2 days prior to immunization significantly enhanced the DTH response. When compared to Freund's complete and incomplete adjuvants, DDA was superior for induction of DTH to inactivated purified measles virus. As DDA could be administered to animals at a site different from the measles virus antigens, or 1 day previously, and still significantly enhance the DTH response, DDA is probably acting more as an immune modulator than as a simple adjuvant. The conditions for an optimal DTH response to measles virus were also shown to be applicable to other enveloped viruses, for example, a strong DTH response was similarly generated to inactivated purified influenza PR8 virus and to herpes simplex virus type I antigens present in plasma membranes isolated from infected Vero cells.