Daniella Dvilanski veterinary student final year Glazgo UK, E.M.S at Dr Neri veterinary surgeon
Vaccine delivery to wildlife: Assessment of efficacyIntroductionVaccination of wildlife populations is important in the control of many infectious diseases that have both economic and public health implications. It can also be valuable in the management of the overabundance of certain wildlife species through immunocontraception. Vaccination of wildlife can be costly, difficult and even dangerous in its implementation, but it has been effective in many areas of the world. Immunisation schemes can aid the conservation of wildlife, especially if it is an endangered species; important examples include the control of plague (Yersinia pestis infection) in the black-footed ferret and control of anthrax (Bacillus anthracis) in Roan antelope and black rhinoceroses. Wildlife species are also an important reservoir for many zoonotic diseases, so vaccination of these species against zoonotic infections is of major public health concern. The highest risk of transmission of diseases from wildlife to humans is through domestic species, such as cattle in the case of badgers infected with tuberculosis or cats and dogs in the case of wild canids such as foxes infected with rabies. This essay will discuss the formulations, modes of delivery, and assessment of efficacy of vaccines against infectious diseases and for immunocontraception in wildlife.
Broadcast vaccination of wildlife is currently an important research area. Scientists are trying to determine the benefits, efficacy and problems of vaccination compared to other methods used, in order to offer the best approach for disease control. The goal of immunization is to increase the individual’s ability to fight disease, and to slow disease transmission (1). In order for a vaccine to offer a valid alternative to other means of disease control, it should provide long-term protection, be safe, stable and cost-effective, and feasible for administration in the wild.
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Later that year, a following study of the BCG efficacy in captive possums was held in New Zealand (8). New Zealand's possums (Trichosurus vulpecula) are a main TB wildlife reservoir, highly susceptible to M. bovis. Previous finding verified wild possums responsiveness to mucosal BCG vaccination, administrated intra- nasally or intra-conjunctively (9). In captivity, lipid based BCG vaccination provided protection, both when given as intra-tracheal instillation of liquid suspension, and when given via inhaled microdroplets (10,11,12,13). This study explored the resilience and the capability of the specific vaccine formulation to protect from M.bovis challenge in the wild, as well as in captivity.
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In the field study, mature possums were captured, marked, and assigned for control and vaccine groups. Following oral BCG vaccination, possums were released and recaptures three months later. Blood lymphocytes levels and lymphocytes proliferation response were higher in the vaccinated group at that point in time. Captures animals were challenged with intra-tracheal installation of M. bovis, after which they were released, bearing a mortality sensing radio-collar. The relative death risk of vaccinated animals was 2.4 times lower than that of the control group. Moreover, the survival probability was higher for the vaccinated group, as shown in the diagram taken from the study (8).
The vaccine has achieved a 60% fall in the relative mortality risk, both in possums with poor body condition as in those with good body conditions in the wintertime, showing stability and efficacy under non-optimal fiend conditions. However, on average, challenged possums survived 2.5 months less than possums naturally infected with TB (4.7 months); stressing the problem of finding a true reflecting assay method that would accurately mimic wild TB disease infection.
Concurrently, a captivity study was held, using thirteen trapped possums. The vaccine group was given palatable oral vaccine formulation for two nights in a row, intended to increase intake chances. Possums were challenged eight weeks later with M.bovis- containing aerosolized microdroplets. The vaccinated group expressed reduced pulmonary pathology and bacterial counts, produced from infected organs, relatively to the control group. Furthermore, fewer animals in the vaccination group exhibited extra-pulmonary macroscopic TB lesions than the control group.
Efforts to find the best way for wildlife vaccine delivery are also markedly seen in the elaborate studies evolving the Rabies disease, a zoonotic viral neuroinvasive disease. In order to find the best vaccination for wild mongoose, a chief wildlife Rabies reservoir, efficacy of two vaccines was tested (17); the common recombinant V-RG vaccine (based on Rabies glycoprotein) and the new SPBNGA-S vaccine.
When efficacy of the V-RG vaccine was tested using a rapid fluorescent focus inhibition test for antibody detection, (RFFIT), no virus neutralizing antibodies (VNA) were detected in either vaccinated or control groups. Subsequently to challenge, all experiment animals were affected from the virus, including the vaccinated group, developing the disease.
Next, the SPBNGA-S recombinant virus vaccine was tested for its efficacy, and the entire vaccinated mongoose were VNA positive. In contrast to the non-vaccinated group, showing Rabies clinical signs, none were seen in the vaccinated group, and no viral antigens were detected in a direct fluorescent antibody test. This study successfully showed the superiority of the newly developed SPBNGA-S recombinant vaccine over the V-RG one.
In light of the SPBNGA vaccine success, further developments took place, generating the SPBNGAS-GAS vaccine, containing an additional copy of Rabies virus glycoprotein gene (18). Efficacy was tested in wild raccoons (Procyon lotor), the most reported rabies reservoir in the North America. SPBNGAS-GAS was found to be better than both original V-RG and the SPBNGA vaccines, both in efficacy and safety, having quicker VNA production with less morbidity and mortality (18,19).
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An especially large-scale research was held in Estonia, where raccoon dogs (Nyctereutes procyonoides) and the red fox (Vulpues vulus) consist of the major rabies wildlife reservoirs (20). As part of the EU rabies control program, the study was devised in order to measure the efficacy of the oral SAG2 vaccine: modified live attenuated vaccine, by looking at rabies epidemiology status before and after vaccination in 2005-06 covering 25,000km 2 of forest.
In 2004 the vaccination program feasibility was tested in a small island with two oral vaccination rounds, spring and fall. In 2005 a bigger trial covering 25,540 km2 was performed in the north of Estonia, applying 505,600 baits, dropped from airplanes.
During the spring and fall of 2006 the whole of Estonia was vaccinated for rabies, using 850,000 baits over 42,992 km2. For the efficacy testing, Fluorescent antibody test (FAT), culture virus isolation and PCR were used, and animals were tested for the presence of Tetracycline in the mandible: biomarker for oral bait uptake. Tetracycline was detected by using inverse microscopy under ultraviolet light, looking at teeth (canine and surrounding alveolar bone) and jawbones.
Finally, Rabies antibodies titres were detected using indirect ELISA.
In the pilot 2004 trial, no rabies was found in the area, based on a sample of 11 animals- raccoons and fox, in which bait intake was 82%. In 2005, out of 97 rabies cases reported in the country, only 16 cases stemmed from the vaccinated area. 73% of tested fox were positive for Tetracycline. In the 2006 cross country trail, only six cases out of the total low number of 17 rabies cases, originated in the vaccinated area. 85% animals were Tetracycline positive and 64% had significant rabies antibodies levels.
ConclusionManipulation of wildlife animals by vaccination, is a form of preventative means for disease management. Immunization creates a situation whereby population becomes resistant to disease, and disease transmission rate is reduced.However, suitable vaccination program is challenging to develop, taking into account the finding of a suitable vaccine, a proper means of delivery, cost and technical matters. Currently, the most effective method for wildlife mass vaccination is via oral baits. However, concerns such as safety to non targeted species still remain unsolved. Essentially, vaccination is suited for a fairly small numbers of pathogens, with low reproductive rate (Ro); in a low- turnover population; and where disease effects mature animals (1). Once a suitable vaccine formulation and delivery method has been chosen and applied, efficacy trials must be conducted in order to verify the effectiveness of the specific immunization program. Such studies were held worldwide covering different vaccination programs, aimed to protect from disease like Rabbis; Tuberculosis; Anthrax; Plague and Lyme, focusing on serology and pathology. Most of the studies covered in this report, have shown positive results of disease control following vaccination. However, factors such as sample size; sex of the animals; sampling and capturing techniques; environmental condition; climate; season and study duration, should all be considered when analyzing the results. The ultimate test for a vaccine efficacy is the population resistance throughout a long period of time, which cannot be reached during the course of standard scientific experiment. The Estonia Rabies study was an exception, covering a perios of three years, thus succeeding in being a reliable source for regarding the efficacy of the vaccine in use.It is interesting to note that little reference of epidemiology and disease breakout modeling has been incorporated in the studies. It could suggested that the use of mathematical modeling would contribute to the understanding and prediction of the disease behavior, thus overcoming some of the time limitation. The above mention models should consider factors such as population movement; climate changes; disease behavior; and population size. By using forecasting information, it might be possible to reach a more accurte vaccination programs, considering thatvaccination is a continuous process wich should be re-assessed, in terms of formulation and delivery.
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