The protective efficacy of immunization against anthrax with Bacillus anthracis protective antigen (PA) combined with different adjuvants was tested in Hartley guinea pigs and CBA/J and A/J mice. Adjuvant components derived from microbial products that were tested included threonyl-muramyl dipeptide (threonyl-MDP); monophosphoryl lipid A (MPL); trehalose dimycolate (TDM); and the delipidated, deproteinized, cell wall skeleton (CWS) from either Mycobacterium phlei or the BCG strain of Mycobacterium bovis. Nonmicrobially derived adjuvants tested included aluminum hydroxide and the lipid amine CP-20,961. In guinea pigs, all adjuvants and adjuvant mixtures enhanced antibody titers to PA as well as survival after a parenteral challenge of virulent B. anthracis Ames spores. In contrast, PA alone or combined with either aluminum hydroxide or CP-20,961 failed to protect mice. Vaccines containing PA combined with threonyl-MDP or MPL-TDM-CWS protected a majority of female CBA/J mice. Statistical analysis of survival data in the guinea pigs indicated that PA-MPL-CWS and PA-MPL-TDM-CWS were more efficacious than the currently licensed human anthrax vaccine.
The present studies demonstrate that antisera directed against Streptococcus pneumoniae type 14 is opsonic for group B streptococci type III in a neutrophile-mediated bactericidal assay. Specificity was demonstrated by the observations that group B streptococci type III and S. pneumoniae type 14 adsorbed the opsonic activity of anti-S. pneumoniae type 14 antisera. Group B streptococci strain 090R (devoid of type antigens) and S. pneumoniae type 3, did not remove the opsonic activity of anti-S. pneumoniae type 14 serum. In vivo studies using a suckling rat model of neonatal group B streptococcal type III sepsis demonstrated that antisera directed against S. pneumoniae type 14 was highly protective.
A micro-agglutination test for the antibodies to Brucella canis produced similar results to those obtained with the standard tube agglutination method in human and canine sera. The micromethod does provide an economical means of screening sera for the presence of antibodies.
Miconazole, a broad-spectrum antimycotic agent with some antibacterial activity, has recently become available for experimental parenteral use in the United States. Its efficacy as an anticandidal drug was tested in adult Wistar rats. A previously established infectious dose of 5 x 10' Candida albicans was intravenously injected into 250-to 300-g animals. This dose was fatal to 95% (20/21) of placebo-treated control animals within the 2-week postinfection observation period. Only 4% (2/53) of rats receiving intramuscular miconazole treatment died. Miconazole therapy in Candida-infected rats at a dosage of 50 mg/kg per day resulted in 85% survival, and, although 100 mg/kg per day was 100% efficacious, it was a relatively large volume to give intramuscularly to a rat. Therefore, 75 mg/kg per day was used as a therapeutic dose, and it gave favorable results in this study. Histological examination of all placebo-treated animals revealed C. albicans and a marked inflammatory response in the kidney, brain, and heart. C. albicans organisms were observed to be very prominent in these tissues by using the Gomori methenamine silver stain, and were cultured from these organs. Miconazole-treated rats that were killed after surviving the 2-week observation period had minimal histopathological changes, and the organisms present did not exhibit the same staining characteristics, nor were they isolated like those in the placebo-treated group
MATERIALS AND METHODSAnimals. Adult Wistar rats (250 to 300 g) were obtained from our noninbred production colony. Animals were housed in groups of five in stainless steel suspension cages. The photo period was automatically controlled, providing 12 h of light and 12 h of dark. Standard laboratory chow and water were provided ad libitum. The environmental temperature ranged from 20 to 250C.Organisms. The strain of C. albicans used in this study was a clinical isolate recovered before initiation of antibiotic therapy. Organisms for animal inoculation were cultured for 18 h in Sabouraud dextrose broth at 370C, harvested by centrifugation, and suspended in 0.01 M phosphate-buffered saline to pH 7.2. The cells were washed three times and resuspended to a concentration of 107 C. albicans per ml in phosphatebuffered saline. Organisms were injected within 30 min of preparation.Injection procedure. All rats were injected with 0.5 ml of the above suspension via the tail vein. Because preliminary studies indicated that rats injected with this dose would die of disseminated candidiasis within 10 days postinjection, the observation period for development of fatal systemic disease was set at 2 weeks. It was important that each animal received the full dose of C. albicans, since those receiving less 321 on May 9, 2018 by guest http://aac.asm.org/ Downloaded from
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