A novel Gammaretrovirus, named Koala retrovirus (KoRV) was identified in koalas in 2000. Subsequent testing has shown that KoRV appears to be widespread throughout the wild koala population in Australia. KoRV is apparently unique in that it is the only known example of an exogenous retrovirus which is actively undergoing the process of endogenisation. While there is currently little direct evidence that KoRV causes overt disease in koalas, it is possible or even likely that KoRV infection plays a significant role in the pathogenesis of various neoplasms and a variety of immunosuppressive disorders which are commonly diagnosed in koalas. It appears that KoRV may have arisen through the cross species transmission of a closely related retrovirus in a native Australian rodent, the grassland melomys. Both of these viruses are closely related to a third retrovirus, Gibbon ape leukaemia virus (GALV). GALV was first isolated in the late 1960＇s from captive gibbons in Thailand that were suffering from leukaemia. To date, the source of GALV remains unknown.

-A new concept of slow "drip feeding" that enables activation of mucosal as well as systemic immunity following parenteral vaccination was demonstrated using Salmonella Dublin in a mouse model. The live vaccine candidate, N-RM25, generated from a wild S. Dublin strain utilising metabolic-drift (spontaneous chromosomal) mutations had a unique sensitivity to bile and restricted growth in the presence of a very low concentration of bile salts No. 3 (0.075% (w/v)) but also had the ability to survive in a high concentration (19.2%) of the substance. Following intraperitoneal administration with 10 7 cfu, N-RM25 colonised and survived (10 1 -10 3 cfu/g) in the liver and spleen of mice for over 24 days without causing disease. A small number of the mutant organisms also penetrated the gall bladder and gut, most likely via the enterohepatic circulation. N-RM25 induced significant levels of serum IgG, IgA and intestinal secretory IgA. A second metabolic-drift mutant (R-NM29) that was rapidly eliminated from the liver and spleen and highly unlikely to penetrate the gall bladder and gut, stimulated some systemic immunity, but induced no mucosal immunity because it did not reach the immune stimulation sites within the gut. In vaccine trials, N-RM25 was significantly more effective in eliminating the homologous challenge bacteria (S. Dublin wild strain FD436) from the internal organs and intestinal lumen when compared to R-NM29 and the negative control. N-RM25 prevented the development of systemic infection and produced 100% protection.Salmonella Dublin / bile / live attenuated vaccine / parenteral vaccination / mucosal immunity

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-In homologous and heterologous challenge trials using calves ≤ 6 weeks old, this comparative study investigated safety, in vivo behaviour and protective properties of oral and intramuscular vaccination with recently developed live attenuated Salmonella Dublin mutant N-RM25. Neither oral nor intramuscular vaccination produced unacceptable side effects. However, the vaccine strain was isolated for up to eight days from the faeces of orally vaccinated calves, but not intramuscularly vaccinated calves. Irrespective of the vaccination route, N-RM25 was isolated in low numbers (≤ 1 × 10 2 cfu/g) from the liver and spleen of calves euthanized at different time points post-vaccination. Vaccination by either route significantly reduced clinical signs and faecal shedding, prevented the development of systemic infection and protected calves from homologous lethal challenge conducted within 14 days post-immunisation. No challenge strain was isolated from major organs and the gut at 18 days post-challenge (except for a single mesenteric lymph node (MLN) specimen from the intramuscular group, but only following enrichment). Following heterologous challenge with a virulent Salmonella Typhimurium strain at 14 and 20 days post-immunisation, all vaccinated animals exhibited significantly fewer clinical signs and colonisation of the intestinal tract than non-vaccinated controls. When compared to oral vaccination, intramuscular vaccination significantly reduced the frequency of faecal shedding of S. Typhimurium (p = 0.0023) and markedly reduced colonisation of MLN. The findings indicate that intramuscular administration of N-RM25 was safer in terms of environmental contamination by the vaccine and provided better early onset protection in young calves following both homologous and heterologous challenge.Salmonella Dublin / metabolic-drift mutant / live attenuated vaccine / early onset protection / calf

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