PubMed · 15818892
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Mohammed Sebaihia, Nicholas R Thomson, Lisa Crossman, Julian Parkhill. 2005. Livelihood hazards.. https://doi.org/10.1038/nrmicro1132
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Induction of immune responses against microbial antigens using DNA is an attractive strategy to mimic the immunity induced by live vaccines. Although DNA vaccines are efficacious in murine models, the requirement for multiple immunizations using high doses in outbred animals and humans has hindered deployment. This requirement is, in part, a result of poor vaccine spreading and suboptimal DC transfection efficiency. Incorporation of a signal that directs intercellular spreading of a DNA-encoded antigen is proposed to mimic live vaccine spreading and increase dendritic cell (DC) presentation. Bovine herpes virus 1 tegument protein, BVP22, is capable of trafficking to surrounding cells. To test the hypothesis that BVP22 enhances spreading and antigen presentation to CD4+ T cells, a DNA construct containing BVP22, fused in-frame to a sequence encoding a T cell epitope of Anaplasma marginale, was generated. A construct with reversed BVP22 sequence served as a negative control. Immunocytometric analysis of transfected primary keratinocytes, human embryonic kidney 293, COS-7, and Chinese hamster ovary cells showed that BVP22 enhanced intercellular spreading by > or = 150-fold. Flow cytometric analysis of antigen-presenting cells (APCs) positively selected from cocultures of transfected cells and APCs showed that 5% of test APCs were antigen-positive, compared with 0.6% of control APCs. Antigen-specific CD4+ T cell proliferation demonstrated that BVP22 enhanced DC antigen presentation by > or = 20-fold. This first report of the ability of BVP22 to increase DNA-encoded antigen acquisition by DCs and macrophages, with subsequent enhancement of major histocompatibility complex class II-restricted CD4+ T cell responses, supports incorporating a spreading motif in a DNA vaccine to target CD4+ T cell-dependent immunity in outbred animals.
Anaplasma marginale infection in Europe has been limited to the Mediterranean and eastern countries, to Austria and to very sporadic cases in Switzerland. There are no reports of its occurrence in the countries north of Switzerland. A severe outbreak of anaplasmosis in August 2002 in a cattle farm in the canton Grisons, Switzerland, north of the Alps, with more than 300 cattle that had to be culled, came unexpected and gave reason to hypothesize presence of an increased yet undetected prevalence of A. marginale in Switzerland. Randomly selected bovine serum samples collected in 1998 and 2003 were tested using a competitive inhibitory ELISA (cELISA) to test the hypothesis. Our validation of the diagnostic sensitivity and specificity of this test, done in the outbreak herd, yielded 99.2 and 83.3%, respectively, probably underestimating the true specificity. The true seroprevalence of anaplasmosis in Swiss cattle determined by cELISA was likely to be zero with upper 95% confidence limits of 2.49% in the canton Grisons and 1.17% in the rest of Switzerland, respectively, in 1998. For 2003, these estimates were even lower. There was no significant difference in apparent prevalences between 1998 and 2003. In search of a possible reservoir, three chamoises out of 46 free ranging wild ruminants from the Swiss National Park, Grisons, tested positive in the cELISA. This reaction is in accordance with A. marginale or a cross reacting agent such as Anaplasma ovis. From our results we conclude that the hypothesis of an increased prevalence of anaplasmosis in cattle in Switzerland must be rejected.
Anaplasmosis, caused by the tick-borne rickettsia, Anaplasma marginale, is an economically important disease of cattle in the United States and worldwide. Cattle that recover from acute infection become carriers in which low or microscopically undetectable A. marginale rickettsemia persists. Tetracycline antimicrobials are currently the only drug used in the US for treatment of acute anaplasmosis. There are currently no drugs specifically licensed for elimination of persistent infections. This study tested the efficacy of three oxytetracycline treatment regimens to clear A. marginale from cattle that were persistently infected. Forty Angus x Simmental steers, aged 6-12 months were experimentally infected with A. marginale. After the steers recovered from acute infection, seroconverted, and were confirmed infected using nested PCR followed by DNA hybridization, the carrier status of each animal was ascertained by sub-inoculation of blood into a separate, splenectomized Holstein calf. The steers were then blocked by bodyweight and randomly assigned as follows to four treatment groups: Treatment A, 300 mg/ml solution of oxytetracycline (Tetradure LA-300, Merial Canada Inc.) administered at 30 mg/kg, by intramuscular (i.m.) injection on day 0; Treatment B, the same 300 mg/ml solution of oxytetracycline administered at 30 mg/kg, i.m. on day 0 and again on day 5; Treatment C, a 200 mg/ml solution of oxytetracycline (Liquamycin LA-200, Pfizer Animal Health) administered at 22 mg/kg, intravenously (i.v.), q 24 h for 5 days (a treatment dose that corresponds with current Office International des Epizooties (OIE) recommendations for treatment prior to export). The fourth group consisted of untreated infected control cattle. All steers were still nested PCR and cELISA positive at 60 days after treatment. Infection was confirmed by subinoculation of blood into a splenectomized Holstein calf. These results demonstrated that the treatment regimens tested failed to clear A. marginale infections in carrier cattle.