Bovis Vaccine Research Articles

A new attenuated Mycobacterium bovis vaccine protects brushtail possums (Trichosurus vulpecula) against experimental tuberculosis infection

Vaccination of wildlife against bovine tuberculosis is being actively considered in countries that have wildlife reservoirs of Mycobacterium bovis infection. A newly attenuated strain of M. bovis (WAg533) was produced as part of a programme to develop a better vaccine than BCG to control tuberculosis in brushtail possums in New Zealand. The vaccine efficacy of WAg533 in possums was compared to BCG using three different methods of inoculation (conjunctival/intranasal, oral and sub-cutaneous) followed by aerosol challenge. Overall, WAg533 was a more potent vaccine than BCG and by two methods of inoculation gave more measures of protection that were significantly different from controls.

Efficacy of tulathromycin for treatment of cattle with acute ocular Moraxella bovis infections

To evaluate the clinical efficacy of a single injection of tulathromycin, compared with saline (0.9% NaCl) solution-treated control calves, for treatment of induced infectious bovine keratoconjunctivitis in calves. Clinical trial. 30 Holstein bull calves ranging from 5 to 6 months old and 75 to 200 kg (165 to 440 lb) with no history of Moraxella bovis infections, no history of M bovis vaccination, and negative results for M bovis on 3 consecutive ocular bacterial cultures. Both eyes of each calf were infected with 1 X 10(10) colony-forming units of piliated M bovis for 3 consecutive days prior to the trial. On day 0, ocular lesion scores were determined for each calf and the calves were weighed and assigned to a treatment (2.5 mg/kg [1.14 mg/lb] of body weight, SC) or control group according to a stratified random allocation based on weight and lesion score. Eyes were stained with fluorescein and photographed daily to record healing. Eyes were evaluated bacteriologically for M bovis on days 0 to 6 and at 3-day intervals thereafter. Median time to ulcer resolution in calves treated with tulathromycin was 9.1 days. More than 50% of control calves still had ulcers at the end of the trial (21 days). Moraxella sp was isolated less often from the eyes of treated calves than from the control calves. By day 10, the treated calves had lower ocular lesion scores than control calves. A single dose of tulathromycin (SC) was an effective treatment of calves with experimentally induced infectious bovine keratoconjunctivitis. The long serum half-life of tulathromycin, along with the results of this trial, suggests that tulathromycin may be a rational choice as a single-injection treatment for infectious bovine keratoconjunctivitis.

The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children

Objectives Bacille Calmette-Guerin (BCG), a live attenuated Mycobacterium bovis vaccine, poses a risk to human immunodeficiency virus (HIV)-infected children; this risk has not been well quantified. We estimate the risk of disseminated BCG disease in HIV-infected children in a setting highly endemic for tuberculosis and HIV. Design and methods We conducted a prospective hospital-based surveillance study in the Western Cape Province, South Africa. Clinical and laboratory-confirmed cases of disseminated BCG disease in children <1 year of age from January 2002 to December 2004 at a referral hospital were used as numerator data. Denominator data for calculations of disseminated BCG risk were obtained through estimating the total number of HIV-infected infants receiving BCG based on the known vaccination coverage in the study setting, combined with population data on the total number of children <1 year of age, the known HIV prevalence amongst women attending public antenatal care facilities and different scenarios (5–15%) for the rate of vertical HIV transmission. Results Nine cases of disseminated BCG disease were identified over the study period, seven of these were in HIV-infected infants. The estimated risk for HIV-infected infants to develop disseminated BCG disease, given a 95% BCG coverage and an HIV prevalence of 12.4–15.4% amongst women, were as follows for different scenarios of vertical HIV transmission: 329–417/100,000 vaccinees (assuming 5% vertical HIV transmission), 164–208/100,000 vaccinees (assuming 10% vertical HIV transmission) and 110–139/100,000 vaccinees (assuming 15% vertical HIV transmission). Conclusions The risk of disseminated BCG disease is increased several hundred fold in HIV-infected infants compared to the documented risk in HIV-uninfected infants. Data on the protective effect of BCG in HIV-exposed and infected children is lacking. Population- and hospital-based surveillance is vitally important to more accurately estimate the safety and benefits of BCG in HIV-exposed and infected infants.

Effect of diminazene block treatment on live redwater vaccine reactions.

One third of the manufacturer's prescribed dose of diminazene has long been used to block treat the South African unfrozen Babesia bigemina and Babesia bovis (redwater) vaccine reactions, with no known adverse effects. It is known that the inhibitory effect of antibabesial drugs is more pronounced in animals inoculated with the frozen vaccine than those with the unfrozen vaccine. Reports of vaccine failures in some animals in which diminazene was used for block treatment of the reactions following inoculation with frozen South African redwater vaccine led us to reinvestigate the required waiting period before treatment and the reduced dose necessary for successful treatment and development of immunity. Results from febrile reactions in cattle following vaccination indicated day 7 as the optimal day for administering block treatment. Treatment of B. bigemina vaccine reactions in cattle on day 7 at a level of 0.35 mg/kg (1/10, fraction of the normal dose) diminazene killed all the parasites while B. bovis vaccine parasites survived treatment using diminazene at levels between 0.35 mg/kg and 1.16 mg/kg. However, various other factors, such as the degree of natural resistance of different cattle breeds and individual animals, the accuracy of diminazene content according to the manufacturer's label claim and the accuracy of the drug dose administered, all influence the successful immunization of animals. Consequently block treating of Babesia vaccines with diminazene on day 7 after vaccination is not recommended.

A DNA prime-live vaccine boost strategy in mice can augment IFN-gamma responses to mycobacterial antigens but does not increase the protective efficacy of two attenuated strains of Mycobacterium bovis against bovine tuberculosis.

The Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine has variable efficacy for both human and bovine tuberculosis. There is a need for improved vaccines or vaccine strategies for control of these diseases. A recently developed prime-boost strategy was investigated for vaccination against M. bovis infection in mice. BALB/c and C57BL/6 mice were primed with a DNA vaccine, expressing two mycobacterial antigens, ESAT-6 and antigen 85 A and boosted with attenuated M. bovis strains, BCG or WAg520, a newly attenuated strain, prior to aerosol challenge. Before challenge, the antigen-specific production of interferon-gamma (IFN-gamma) was evaluated by ELISPOT and antibody responses were measured. The prime-boost stimulated an increase in the numbers of IFN-gamma producing cells compared with DNA or live vaccination alone, but this varied according to the attenuated vaccine strain, time of challenge and the strain of mouse used. Animals vaccinated with DNA alone generated the strongest antibody response to mycobacterial antigens, which was predominantly IgG1. BCG and WAg520 alone generally gave a 1-2 log10 reduction in bacterial load in lungs or spleen, compared to non-vaccinated or plasmid DNA only control groups. The prime-boost regimen was not more effective than BCG or WAg520 alone. These observations demonstrate the comparable efficacy of BCG and WAg520 in a mouse model of bovine tuberculosis. However, priming with the DNA vaccine and boosting with an attenuated M. bovis vaccine enhanced IFN-gamma immune responses compared to vaccinating with an attenuated M. bovis vaccine alone, but did not increase protection against a virulent M. bovis infection.

An experimental vaccine for calf pneumonia caused by Mycoplasma bovis: clinical, cultural, serological and pathological findings

A single dose of vaccine for Mycoplasma bovis pneumonia, inactivated with saponin, was inoculated subcutaneously into 3–4 week-old calves. The calves were challenged 3 weeks later with a virulent strain of M. bovis on two occasions within 24 h using the aerosol route. The calves were monitored for clinical signs and serological responses then post mortemed 3 weeks after challenge. The vaccine was shown to be highly immunogenic in calves and did not cause adverse effects. Vaccinated calves showed few clinical signs while all unvaccinated calves developed signs of pneumonia. There was a significant decrease in body weight gain in unvaccinated calves compared to vaccinates and a significant increase in lung lesions and rectal temperatures in unvaccinated calves. The vaccine also reduced the spread of M. bovis to internal organs. In conclusion the M. bovis vaccine produced a significant level of protection against a large virulent challenge.

New generation vaccines and delivery systems for control of bovine tuberculosis in cattle and wildlife

Advances in the understanding of protective immune responses to tuberculosis are providing opportunities for the rational development of improved vaccines for bovine tuberculosis. Protection requires activation of macrophages through stimulation of a Th 1 type immune response. Ideally, a vaccine for cattle should induce protection without causing animals to react in a tuberculin test when exposed to Mycobacterium bovis. A number of new tuberculosis vaccines including attenuated M. bovis strains, killed mycobacteria, protein and DNA vaccines have been developed and many of these are being assessed in cattle. The requirements for a tuberculosis vaccine for wildlife differ from those for cattle. The major goal of a wildlife vaccine is to prevent the transmission of M. bovis to cattle and other wildlife. Although there are a number of technical problems associated with the development of a vaccine delivery system for wildlife, attenuated M. bovis vaccines administered via oral baits or aerosol spray to possums have already been shown to reduce the severity of a subsequent M. bovis infection.

Genetic susceptibility to tuberculosis.

Tuberculosis, caused by the human pathogen Mycobacterium tuberculosis (M. tuberculosis), affects an estimated 8 million people annually, resulting in approximately 2 million deaths. Human genetic variability is an important modulator of tuberculosis susceptibility. This review will discuss candidate susceptibility genes that have been implicated in tuberculosis susceptibility across various ethnic groups and epidemiological settings. Evaluating the genetic variants of tuberculosis susceptibility genes will provide us with a better understanding of the disease mechanisms in tuberculosis. Ultimately, such genetic studies may lead to the development of effective alternative treatments to cope with the growing problem of tuberculosis infections due to the AIDS pandemic, the emergence of multidrug resistant M. tuberculosis, and the limited efficacy of Mycobacterium bovis (BCG) vaccination.

Vaccination of cattle against Mycobacterium bovis

Protection of cattle against bovine tuberculosis by vaccination could be an important control strategy in countries where there is persistence of Mycobacterium bovis infection in wildlife and in developing countries where it is not economical to implement a ‘test and slaughter’ control programme. Early field trials with Bacille Calmette Guerin (BCG) M. bovis vaccine in cattle produced disappointing results, with induction of tuberculin skin-test reactivity following vaccination and low levels of protection. However, recent studies using a low dose of BCG vaccine in cattle have produced more encouraging results and field trials should now be carried out in developing countries to determine whether this low dose BCG vaccination strategy will reduce the spread of infection. The options for new candidate tuberculosis vaccines have increased markedly in the last decade with the advent of new attenuated strains of M. bovis, and sub-unit protein and recombinant DNA vaccines. Some of these new types of vaccines have recently been tested in cattle. New attenuated M. bovis vaccines induced greater protection than BCG vaccine in cattle which had been sensitized to environmental mycobacteria prior to vaccination. In contrast, it has proved difficult to stimulate appropriate immune responses in cattle necessary for protection with sub-unit protein and recombinant DNA vaccines and better immunological adjuvants are required for these types of vaccines. Progress in the development of new tuberculosis vaccines has been very rapid in the past decade and the prospects for vaccination to control and eradicate bovine tuberculosis are encouraging.

Abstract

Immunisation against acidosis in sheep Shu, Q., Gill, H. S., Leng, R. A. & Rowe, J. B. (2000) Immunisation with a Streptococcus bovis vaccine administered by different routes against lactic...

Immunization with a Streptococcus bovis Vaccine Administered by Different Routes Against Lactic Acidosis in Sheep

Streptococcus bovis is an important lactic acid bacterium in the rumen, which contributes to the development of lactic acidosis. This study was designed to test the efficacy of immunization with S. bovis primed either intramuscularly (i.m.) or intraperitoneally (i.p.) against lactic acidosis. Forty-five wethers were allocated to three treatment groups. Two groups were injected with a S. bovis vaccine by either the i.m. or i.p. route for primary immunization; both groups were further immunized by the same route(s) (oral and/or i.m.) for boosters. The third group was not immunized (control).Antibody concentrations were measured in saliva prior to and following animals being fed a grain diet, and also in the rumen fluid, before the animals were suddenly introduced to a grain diet. The average antibody concentration in the animals of the i.m. group was higher than the i.p. group (P< 0.05). The antibody concentration in the rumen fluid of immunized sheep was higher than the control animals (P< 0.01). The difference in the rumen fluid antibody concentration between the i.m. and i.p. groups was not statistically significant (P> 0.05). In the i.m. group, there was a significantly greater feed intake, higher rumen pH, lower diarrhoea scores, and less increase in blood packed cell volume following grain feeding than in the animals of the control group. The severity of diarrhoea and the increase of blood packed cell volume in the animals of the i.p. group were also less than in the animals of the control group. The results suggest that the risk of lactic acidosis can be reduced by immunization against S. bovis, and that the immunization primed i.m. is more effective than the immunization primed i.p.

Effect of antibiotics and anti-inflammatory agents on the purified protein derivative response in the rat.

We investigated the effects of several antibiotics and anti-inflammatory agents on the purified protein derivative (PPD) response in the rat. Animals were immunized with Mycobacterium bovis vaccine BCG. Antibiotics and anti-inflammatory drugs were administered at therapeutic doses for 10 d. Chloramphenicol, erythromycin, aspirin and ibuprofen suppressed the PPD response, but penicillin and acetaminophen had no significant effects.

Immunohistological study of the cutaneous delayed type hypersensitivity reaction in sheep

The cutaneous delayed type hypersensitivity (DTH) reaction may be experimentally initiated both as an in-vivo technique for the study of the cell mediated arm of the immune system, and also as an accurate clinical test of the functional capacity of this part of the immune response. This study was performed to fully evaluate the immunohistological characteristics of the normal DTH reaction utilising an ovine model. Six clinically healthy sheep were inoculated with an intradermal Mycobacterium bovis vaccine. After 21 days, they were challenged with multiple intradermal injections of a purified protein derivative (PPD) of M. bovis in the hairless skin of the medial thigh. Simultaneous contralateral injections of sterile diluent were performed to provide control material. The resulting lesions were measured for increase in skin thickness and biopsied at 2, 7, 24, 48, 72, and 96 h post injection. The biopsies were divided, and stained both histochemically and with monoclonal antibodies directed against lymphocyte subsets, macrophages, and B cells. The DTH reaction was maximal at 72 hours post challenge, and was largely characterised by an initial influx of polymorphonuclear neutrophil (PMN) cells, after which there was an accumulation of αβ T cells. The number of macrophages within the lesion declined with the progression of the reaction. B cells and γδ T cells did not appear to play a major role in the response. Fibrin was a marked component of the reaction at later time points.

Studies on failure of T strain live Babesia bovis vaccine.

Field investigations of the protection afforded by the Australian live Babesia bovis vaccine used in the early 1990s (T strain) revealed inadequate vaccine-induced protection in certain herds. Vaccination/challenge trials using 207 experimental cattle were conducted to evaluate the protection afforded by T strain B bovis against field isolates from these herds. The trials investigated whether isolates that could 'break-through' T strain immunity were present in the field, the ability or inability of specific cattle to develop protective immunity after vaccination with T strain and the effect of attenuation and maintenance procedures on the immunogenicity of T strain. The results showed that B bovis parasites present early in the process of attenuation of T strain were more protective than those remaining late in the process. They also showed that cattle from properties experiencing vaccine failures were less protected by T strain vaccination than Bos taurus cattle randomly selected from the general population if vaccinated with highly attenuated T strain. A hypothesis is offered to explain these findings.

Efficacy of an Australian Babesia bovis vaccine strain in Malawi.

Three calves vaccinated with the Australian Ka strain of Babesia bovis were fully protected against experimental infection with an isolate from a farm on which four of 210 vaccinated cattle had died from B bovis infection. A degree of cross protection against the isolate was demonstrated in one calf which had been infected previously with Babesia bigemina.

Investigations of breakdowns in protection provided by living Babesia bovis vaccine

Field investigations of protection afforded by live Babesia bovis vaccine in Australia revealed that a ninefold increase in vaccine failures occured in the period from 1985 to 1990. Laboratory trials using 189 experimental cattle were conducted to evaluate the protection afforded by the Babesia bovis strain used in the commercial vaccine during this time. Four isolates from clinical cases of babesiosis in vaccinated cattle were assessed. The results showed that the strain used in the vaccine during the 5 year period was poorly protective against three isolates while a recently isolated and prepared vaccine strain was strongly protective. Circumstantial evidence is provided that indicates the vaccine failures were due to change in the field populations of Babesia bovis, rather than change in the strain used in the vaccine. Implications of the results for the future of Babesia bovis vaccines are discussed.

Bovine babesionsis: Failure to induce interferon gamma production in response to Babesia bovis antigens in cattle

The immune response to Babesia bovis infection or vaccination ws evaluated by measuring antibody and interferon gamma (IFN-γ) production to protective recombinant and crude native B. bovis antigens. Cells from vaccinated or infected cattle failed to produce detectable IFN-γ when stimulated with B. bovis antigens in vitro. In contrast, antibody was induced by protective recombinant B. bovis antigens. These findings are consistent with the argument that immunity to B. bovis infection is correlated most strongly with humoral rather than cell-mediated immune responses.

Successful vaccination against Boophilus microplus and Babesia bovis using recombinant antigens.

Current methods for the control of the cattle tick Boophilus microplus and the agent of bovine babesiosis, Babesia bovis are unsatisfactory. Effective immunological control of both parasites would have great advantages. However, naturally acquired immunity to the tick is generally unable to prevent serious production losses. A vaccine against the tick, based on a novel form of immunization, is being developed. A protective antigen has been isolated from the tick, characterized and produced as an effective, recombinant protein. A vaccine incorporating this antigen is currently undergoing field trials. In the Australian situation, improved tick control will probably increase endemic instability with respect to B. bovis. Fortunately, a trivalent, recombinant B. bovis vaccine has also been developed. This too is now undergoing pre-registration field trials.

Failure of a recombinant Babesia bovis antigen to protect cattle against heterologous strain challenge

Groups of cattle were inoculated subcutaneously with (i) a recombinant DNA-derived Babesia bovis protein (KaBbl-GZ) fused to beta-galactosidase and combined with adjuvants, or (ii) native beta-galactosidase (GZ) plus adjuvant, or (iii) adjuvant only or (iv) a live, attenuated B bovis vaccine. KaBbl-GZ was produced in the lambda gt11-amp3 system as a 5-10 kD babesial polypeptide linked to GZ. KaBbl has previously been shown to be an immunodominant antigen of B bovis, localised at the apex of the parasite, and present in a range of B bovis strains. High levels of GZ antibodies were observed in KaBbl-GZ and GZ inoculated cattle, but specific KaBbl antibodies could not be detected by ELISA. Five months after primary inoculation, all cattle were blood challenged with a virulent heterologous B bovis strain. Despite four inoculations with KaBbl-GZ, significant protection against the challenge was not observed.

Moraxella bovis vaccine containing M. bovis protease produced by fermentation

Moraxella bovis vaccine containing M. bovis protease produced by fermentation