Vaccination against bovine herpes mammillitis virus infections in guinea pigs.

Bovine herpes mammillitis virus or bovine herpesvirus type 2 (BHV-2) causes ulcerative lesions on the teats and udders of infected cows. Since no commercial vaccine is available for this disease, we investigated certain experimental BHV-2 vaccines against this virus in infected guinea pigs. Vaginally infected guinea pigs get severe, self-limiting vaginal infections characterized by erythema and swelling and the production of measurable vaginal virus titers. Two vaccine approaches were investigated: vaccination with wild-type (WT) virus by the subcutaneous route, and vaccination either subcutaneously or intravaginally with a thymidine kinase (TK) deficient (TK-) virus. The TK- strain was prepared by passage of BHV-2 in the presence of the potent TK-dependent antiviral agent 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU). The antiviral activity of FMAU against the virus in plaque reduction assays changed from 0.05 to 2 microM at the same time that the TK activity of the mutant virus decrease to 7% of WT virus TK activity. Subcutaneous vaccination of guinea pigs with WT and TK- viruses did not induce vaginal infection. Primary vaginal infection (vaccination) with the TK- virus led to greatly reduced lesion severity compared to vaginal infection with the WT virus. However, the amount of vaginal virus titers recovered during these primary infections was similar for both TK- and WT viruses, indicating that both viruses had equal infecting potential. Thirty days after vaccination the animals were re-infected intravaginally with WT virus. The vaccinated animals showed dramatically reduced lesion severity and low recoverable virus titers compared to age-matched nonvaccinated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of lethal Pichinde virus infections in weanling LVG/Lak hamsters with ribavirin, ribamidine, selenazofurin, and ampligen.

A lethal Pichinde (An 4763 strain) virus infection was produced in 3-week-old random-bred Golden Syrian (LVG/Lak strain) hamsters inoculated intraperitoneally with virus, causing mortality in 6-9 days. High virus titers (> or = 10(7.5) cell culture infectious doses/g) were present in visceral organs, serum, brain and salivary glands near the time of death. Intraperitoneal treatments with ribavirin (10 and 32 mg/kg) and ribamidine (32, 100, and 320 mg/kg) for 10 days starting 24 h after virus challenge significantly decreased mortality and reduced virus titers by 100- to > 10,000-fold in liver, spleen, brain, and serum. Serum alanine aminotransferase (an indicator of liver damage) was also reduced in animals treated with the two compounds (ribavirin at 32 mg/kg; ribamidine at 100 and 320 mg/kg). Intraperitoneal selenazofurin (1-100 mg/kg per day for 10 days) and ampligen (0.5 and 5 mg/kg every other day for 5 injections) treatments provided neither protection from the lethal infection nor increased mean survival times. In fact, selenazofurin was overtly toxic, causing death of uninfected hamsters at 32 and 100 mg/kg. The random-bred LVG/Lak hamster appears to be a viable and cost-effective model for evaluating new therapies for arenavirus infections.

Treatment of murine cytomegalovirus infections in severe combined immunodeficient mice with ganciclovir, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine, interferon, and bropirimine.

Severe combined immunodeficient (SCID) mice were found to be highly susceptible to murine cytomegalovirus (MCMV) infection. Treatment of infected mice with ganciclovir (12.5, 25, and 50 mg/kg of body weight for 10 days) starting 24 h after virus challenge resulted in delays in death by 2 to 8 days, and no animals survived the infection. (S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) was much more potent, with doses of 1, 3.2, and 10 mg/kg/day (for 10 days) increasing the mean survival time by 15 to 30 days. Twenty-day treatments with HPMPC starting 5 days after virus inoculation increased the mean survival time by 24 to 32 days, with once-weekly (50-mg/kg) treatments being equivalent to daily (10-mg/kg) treatments. Delays in the development of liver, lung, and spleen virus titers in ganciclovir- and HPMPC-treated groups correlated with extensions in the mean survival times relative to the survival times of the placebo controls. The two compounds were approximately equally toxic to uninfected BALB/c mice treated for 10 days, causing 80 to 100% mortality after a dose of 150 mg/kg and 0% mortality after a dose of 75 mg/kg. Thus, the relative therapeutic index of HPMPC was 50-fold greater than that of ganciclovir. Recombinant alpha interferon delta 4 alpha 1/alpha 2 (1 x 10(4) and 5 x 10(4) units per mouse per day) and bropirimine (100 and 300 mg/kg/day) provided no protection from the lethal MCMV infection. The severe combined immunodeficient mouse MCMV infection is an important new model that will permit chemotherapy regimens to be studied over several months.