Effects of monoclonal antibody combined with ganciclovir or (S)-1-[3-hydroxy-(2-phosphonylmethoxy)-propyl]cytosine against murine cytomegalovirus infections in cell culture and in severe combined immunodeficient mice.
The effects of monoclonal antibody used in combination with ganciclovir (GCV) or (S)-1-[3-hydroxy-(2-phosphonylmethoxy)propyl]cytosine (HPMPC) against murine cytomegalovirus (MCMV) were determined in vitro and in vivo, in mice. The antibody and drug were added to cell cultures 24 h after MCMV adsorption so as not to affect the initial infection rate. The antibody (at 1.25-20 micrograms/ml) combined with GCV (0.3-5 microM) or HPMPC (0.008-0.125 microM) caused synergistic inhibition of virus yield in C127I cells. No toxic effect on cell growth in culture was observed at these antibody/drug combinations. The effects of antibody and GCV treatments were studied in MCMV-infected severe combined immunodeficient (SCID) mice. Antibody treatments (2.5 mg/kg/day) given by intraperitoneal injection every 3 days starting 24 h after virus inoculation extended survival time by 1 day relative to placebo-treated animals. Once daily, intraperitoneal treatments with GCV (25 and 50 mg/kg/day) for 7 days starting at 24 h after virus inoculation extended survival time 9-11 days. The combination of antibody plus GCV was only slightly better than GCV alone, indicating an additive interaction.
Smee
D F
DF
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322-5600, USA.
Sugiyama
S T
ST
Sidwell
R W
RW
Barnett
B B
BB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000077404:Cidofovir; D003131:Combined Modality Therapy; D003470:Culture Media; D003586:Cytomegalovirus Infections / Q000628:therapy* / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D016867:Immunocompromised Host / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D003470:Culture Media; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir