Safety, efficacy and cross-protectivity of a live intranasal aerosol haemorrhagic septicaemia vaccine

The safety, efficacy and cross-protectivity of a live intranasal aerosol haemorrhagic septicaemia vaccine containing Pasteurella multocida serotype B:3,4 were tested in young cattle and buffaloes in Myanmar, where more than 1.5 million animals had been inoculated with this vaccine between 1989 and 1999. A recommended dose of 2 x 10(7) viable organisms was used for the efficacy test. The administration of 100 times the recommended dose to 50 cattle and 39 buffalo calves was innocuous. Seven months after they were vaccinated, three of three buffaloes were protected and 12 months after they were vaccinated, three of four buffaloes were protected against a subcutaneous challenge with serotype B:2 which killed three of three unvaccinated buffaloes. Twelve months after they were vaccinated, eight of eight cattle survived a serotype B:2 challenge, which killed four of four unvaccinated controls. The vaccinated cattle had developed serum antibodies detectable by the passive mouse protection test. Indirect haemagglutination tests on sera taken from cattle 10 days and five weeks after they were vaccinated showed high titres of antibodies. The serum of vaccinated cattle cross-protected passively immunised mice against infection with P. multocida serotypes E:2, F:3,4 and A:3,4.     

Safety and efficacy of an oil-adjuvant vaccine against haemorrhagic septicaemia in buffalo calves: cross-protection between the serotypes B:2,5 and E:2,5.

The safety, efficacy and duration of immunity of an improved oil-adjuvant vaccine against haemorrhagic septicaemia, containing inactivated cells of Pasteurella multocida serotype B:2,5, were tested in young buffalo calves in Pakistan. For safety testing, five buffalo calves were vaccinated intramuscularly with twice the normal dose, and six weeks later with a normal dose. Except for a transient rise in rectal temperature at six hours after the vaccinations, no systemic reactions were observed. The buffaloes remained in good condition and had a normal appetite. No local reactions were observed at the injection site. For efficacy testing two trials were carried out. In the first, buffalo calves were vaccinated intramuscularly either with two doses two-and-a-half months apart, or with a single dose, or left unvaccinated. They were challenged subcutaneously with virulent P multocida after eight, 13 or 15 months. After challenge at eight months the four buffaloes given two doses and the buffalo given one dose were protected, whereas the control animal developed the typical signs of the disease. After the challenges at 13 and 15 months, the vaccinated animals were still protected whereas the control animals died. In the second trial, buffalo calves were vaccinated intramuscularly either with two doses two months apart, or with a single dose at two months or left unvaccinated. The buffaloes were challenged after eight or 14 months. After challenge at eight months the four control animals died, whereas three of the four buffaloes given a single dose were protected. After challenge at 14 months, the three control animals died, whereas four of the five buffaloes given two doses and both the buffaloes given a single dose were protected. To test for cross-protection against the heterologous serotypes E:2,5 and B:3,4, groups of mice were vaccinated once or left unvaccinated. Four weeks later, the vaccinated and control groups were challenged with a dilution series of the different challenge cultures. The vaccine appeared to induce protection against challenge with different strains of serotypes B:2,5 and E:2,5 but not against strains of serotype B:3,4.     

Immunity to leptospirosis: renal changes in vaccinated cattle given challenge inoculum.

Resistance to renal leptospirosis was demonstrated in cattle vaccinated with Leptospira interrogans serotype pomona bacterin. Fewer vaccinated cattle given challenge inoculum of virulent serotype pomona leptospires 12 months after vaccination had kidneys with gross focal lesions in the cortex than did nonvaccinated controls. Histopathologic changes characteristically associated with renal leptospirosis occurred less frequently and renal tissue damage was less severe in vaccinated cattle than in nonvaccinated controls. The isolation of serotype pomona from only 1 of 29 vaccinated cattle, compared to 7 isolations from 11 nonvaccinated cattle, at 26 days after challenge inoculum was given, indicated that mild renal infection occurred only infrequently in vaccinated cattle. It appeared that challenge inoculation of vaccinated cattle with virulent serotype pomona leptospires stimulated an accelerated secondary immune response in which immunity limited the multiplication of leptospires in the kidney.     

Prevention of experimental haemorrhagic septicaemia with a live vaccine

Pasteurella multocida serotype B:3,4 isolated from a fallow deer in England was used as a vaccine to prevent haemorrhagic septicaemia. The deer strain was less virulent for calves than typical serotype B:2 of haemorrhagic septicaemia strains. It elicited antibodies in cattle that protected mice against serotype B:2 infection. The live deer vaccine containing 2 X 10(7) viable organisms per dose was used to immunise calves. Six months after vaccination, five of six calves were protected against serotype B:2 challenge. Two calves challenged nine months after vaccination survived the same challenge. The live vaccine was more efficacious than an alum precipitated vaccine in protecting calves against B:2 challenge.     

Use of a toxoid vaccine to protect goats against intradermal challenge exposure to Corynebacterium pseudotuberculosis

Two groups of male, 9-week-old goats (5 goats/group) were vaccinated subcutaneously with formalized exotoxin of Corynebacterium pseudotuberculosis, with Freund's incomplete adjuvant. Each goat was given 2 vaccinations, 2 weeks apart. At each vaccination, each group 1 goat was given 0.5 ml of toxoid, and each group 2 goat was given 1 ml of toxoid. Twenty days after the 2nd vaccination, vaccinated goats and 5 nonvaccinated 12-week-old goats (controls) were inoculated intradermally (challenge exposed) with live C pseudotuberculosis, monitored for 13 weeks, and euthanatized. At necropsy, 5 of the 10 vaccinated goats did not have C pseudotuberculosis lesions, 3 had abscesses limited to the inoculation site and draining lymph node, and 2 had disseminated bacterial lesions. Of the 5 nonvaccinated controls, 4 had disseminated abscesses and 1 had a single abscess in an internal node. Serologically, 9 of the 10 vaccinated goats developed positive (greater than or equal to 1:8) antibody titers against the exotoxin within 1 week after inoculation; the 10th goat seroconverted 2 weeks after inoculation, whereas control goats required 3 weeks to develop a positive antibody response. Therefore, early during an infection with C pseudotuberculosis, antibodies against the exotoxin may protect a goat against spread of the organism. All goats were injected intradermally before challenge exposure, 10 days after challenge exposure, and at 4, 8, and 12 weeks after challenge exposure with a skin-test reagent composed of fragmented bacterial cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Persistence of the protective immunity to Schistosoma japonicum in Chinese yellow cattle induced by recombinant 26kDa glutathione-S-transferase (reSjc26GST)

To observe the long lasting effect of the recombinant Sj26GST sub-unit vaccine against Schistosoma japonicum in cattle, animals aged from 5 to 12 months were vaccinated with reSjc26GST, and were challenged by natural infection 6 months or 12 months after vaccination. Worm burdens per cattle and egg burden in tissue (per gram) of cattle with or without vaccination were compared. The results showed that anti-reSjc26GST antibodies were produced in vaccinated cattle. Following natural infection, the vaccinated and the control non-vaccinated cattle were all found to be infected with S. japonicum. A 30% reduction in worm number was observed in the vaccinated cattle when compared with the control cattle. The anti-fecundity effect was characterized by an average of 60% decrease in eggs deposited in the liver of vaccinated cattle; such a decrease is obviously very significant. In addition to the anti-fecundity effect induced in the vaccinated cattle, the number of miracidum hatched per 50 g faeces and the number of eggs released in intestinal tissues per gram were reduced or decreased. Results suggested that the immune responses induced by reSjc26GST in cattle were similar to that in buffaloes and in pigs. In addition, our result demonstrated that the lasting effect of immunity to S. japonicum induced in cattle after vaccination with reSjc 26 GST could persist at least 12 months.     

FAILURE OF A SINGLE DOSE OF BRUCELLA ABORTUS STRAIN 19 VACCINE TO PROTECT CATTLE WHEN GIVEN EARLY IN CALFHOOD

SUMMARY Groups of heifer calves were vaccinated subcutaneously with the standard dose of strain 19 at the age of 3 to 5 weeks or 5 months. Twelve months after primary vaccination a group of the younger vaccinates were revaccinated with a small dose of strain 19 via the conjunctival sac. The effectiveness of vaccination was assessed by challenge with virulent B. abortus after 5 to 6 months of pregnancy. Animals vaccinated at 3 to 5 weeks, but given no intraconjunctival boost, were not effectively protected, but the group receiving the boost were at least as resistant as those which received the subcutaneous dose at 5 months. The intraconjunctival boost caused only slight and transient serological responses in a few animals.     

Efficacy of intranasal vaccination of field buffaloes against haemorrhagic septicaemia with a live gdhA derivative Pasteurella multocida B:2

The efficacy of an intranasal haemorrhagic septicaemia vaccine containing live gdhA derivative Pasteurella multocida B:2 was tested in buffaloes in Sabah. Sixty buffaloes, kept grazing in the field with minimal human intervention were devided into three groups of 20 buffaloes per group. Buffaloes of group 1 were exposed intranasal to 5 ml vaccine containing 10(6) CFU/ml of live gdhA derivative P multocida B:2. Buffaloes of group 2 were not exposed to the vaccine but exposed to PBS and were allowed to commingle and graze in the same field as the buffaloes of group 1 while buffaloes of group 3 were similarly exposed to PBS and were grazing separately. Booster was on group 1, two weeks later. Twelve months after the first vaccination, three buffaloes from each group were brought into the experimental house and challenged subcutaneously with 10(9) CFU/ml of live wild-type P multocida B:2. All challenged buffaloes of groups 1 and 2 survived with only mild, transient signs while all control unvaccinated buffaloes developed severe signs of haemorrhagic septicaemia and were euthanased between 28 hours and 38 hours postchallenge with signs and lesions typical of haemorrhagic septicaemia. These data showed that the gdhA mutant strain, given intranasally as two doses two weeks apart, successfully induced systemic immunity in exposed buffaloes and also led to spread of vaccine strain to the in-contact animals, where it acted as an effective live vaccine to protect both exposed buffaloes and in-contact buffaloes against challenge with the virulent parent strain.     

Immune responses of cattle following vaccination with living and non-living Babesia bovis antigens

Twenty-four yearling Hereford (Bos taurus) cattle were vaccinated against Babesia bovis using either live parasites or non-living antigens obtained from the supernatant of in vitro cultures. A single dose of live parasites was given subcutaneously, while the non-living supernatant antigen (NLSA) was combined with saponin and 2 doses given, 2 weeks apart. Following vaccination with live parasites, serum antibodies remained at high levels for 6 months, but the lymphocyte transformation response was low and lasted only 10-18 days. In contrast, NLSA vaccination was followed, after 21-28 days, by a peak of serum antibodies which then slowly declined. The lymphocyte transformation response in these animals was much higher and persisted for 6 months. Following heterologous challenge all unvaccinated cattle had severe reactions and required treatment to prevent death. Cattle vaccinated with live parasites had mild reactions with only 1 of the 12 requiring treatment. Cattle vaccinated with NLSA were only partially protected and 6 of the 12 required treatment.     

Protection of cattle against heartwater in Botswana: comparative efficacy of different methods against natural and blood-derived challenges

Five groups of Tswana-cross castrated male cattle between 20 and 30 months of age (a total of 158 animals) were transported from a ranch in a heartwater-free area of south Botswana to a feedlot near Gaborone in the east of Botswana where heartwater is endemic. On arrival, one group was vaccinated intravenously with the Onderstepoort sheep blood heartwater vaccine, one group was vaccinated intravenously with the new Onderstepoort tick-derived heartwater vaccine and a third group was vaccinated subcutaneously with this tick-derived vaccine. Vaccine reactions were blocked with long acting oxytetracycline on the first day of fever. A fourth group had a series of injections of long acting oxytetracycline on days 0, 7, 14 and 21 after arrival, and a fifth served as untreated controls. The animals remained at the feedlot for 65 days during which time they faced a low level of challenge by Amblyomma hebraeum ticks. None contracted heartwater and so they were then challenged, together with a further group of control cattle, with a dose of the sheep blood vaccine. Some animals in all groups had severe heartwater reactions and died despite therapy, but 76.7 per cent, 64.5 per cent and 74.3 per cent of the cattle in the blood vaccine, intravenous tick vaccine and long acting oxytetracycline groups respectively were resistant to challenge, compared with 48.3 per cent of the subcutaneous tick vaccine group and 36.4 per cent of the controls. It was concluded that intravenous vaccination of susceptible adult cattle with either the blood or the tick-derived vaccine needs careful monitoring in the month after vaccination and does not necessarily result in immune animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

An enzyme-linked immunosorbent assay for detection of Brucella abortus in cattle using monoclonal antibodies

One group of 24 cattle was vaccinated with the usual calfhood dose of B. abortus strain 19 and a further 27 cattle were similarly vaccinated but as adults. Twenty-four cattle (12 from each group) and a control group of 12 cattle were subsequently challenged with B. abortus strain 544. Two monoclonal antibodies (MA (A) and MA (B) ) conjugated to horseradish peroxidase were used independently in a competitive enzyme-linked immunosorbent assay (ELISA) to test the serums. After vaccination with B. abortus strain 19, the performance of the monoclonal antibodies was in general agreement with the CFT as fewer calfhood vaccinates were positive 12 weeks after vaccination to the ELISA with MA (A) and MA (B) than adult vaccinates. After challenge, MA (A) and MA (B) ELISA tests detected the infected cattle earlier than the CFT, but more positive reactions occurred in the cattle that proved uninfected at slaughter.     

Brucella abortus-specific immunoglobulin in isotypes in serum and vaginal mucus from cattle vaccinated with strain 19 and challenge exposed with virulent strain 2308

The immunoglobulins (IgG1, IgG2, IgM, and IgA) of the Brucella-specific antibody response of 69 crossbred beef heifers were studied after Brucella abortus strain 19 vaccination and strain 2308 challenge exposure. The immunoglobulin isotype responses in serum and vaginal mucus were measured by use of fluorescent immunoassay. Serum antibody responses were detected also by 3 standard serologic tests (complement fixation [CF], Rivanol precipitation, and the CARD test] and 2 primary bindings assays that detect IgG antibodies. One month after vaccination, mean antibody titers for all immunoglobulin isotypes were higher for vaccinated cattle (n = 46) than for nonvaccinated controls (n = 23). After vaccination, IgA antibody responses in vaccinated cattle were only 2-fold higher than those for controls, whereas IgG1, IgG2, and IgM antibody responses were 3- to 90-fold greater than those for controls. Measurement of IgA antibody responses classified 21 of 39 vaccinates as seropositive after vaccination, whereas the other isotypes classified 28 or 34 cattle as seropositive. Three months after challenge exposure, the mean antibody responses for each isotype were higher in cattle that aborted or were culture positive than in cattle that did not abort and were culture negative. Although IgG1, IgG2, and IgM antibody titers were each of benefit in identifying B abortus-infected cattle, it did not appear that the magnitude of the antibody responses provided sufficient discrimination between S19-vaccinated cattle and S2308 challenge-exposed cattle. Serum IgA antibody responses were 10-fold higher after challenge exposure than after vaccination and may be a response to mucosal infection with the virulent organism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response of cattle persistently infected with noncytopathic bovine viral diarrhea virus to vaccination for bovine viral diarrhea and to subsequent challenge exposure with cytopathic bovine viral diarrhea virus

Nine steers persistently infected with noncytopathic bovine viral diarrhea (BVD) virus were allotted into 3 groups (3 cattle/group). Cattle in group A were vaccinated with a modified-live BVD virus vaccine of porcine cell origin, cattle in group B with a modified-live BVD virus vaccine of bovine cell origin, and cattle in group C with a killed BVD virus vaccine of bovine cell origin. Detrimental effects due to vaccination were not seen. Six weeks after vaccination, the steers were challenge exposed with a cytopathic BVD virus. All steers developed mucosal disease after challenge exposure, produced antibodies that neutralized various isolates of BVD virus, and remained persistently infected until death. Steers given killed virus vaccine had a minimal neutralizing-antibody response and developed mucosal disease as quickly as reported for challenge-exposed, nonvaccinated, persistently infected cattle. Steers given modified-live virus vaccines had higher neutralizing-antibody response and longer intervals from challenge exposure to development of mucosal disease. The specificity of the neutralizing-antibody response differed between groups of vaccinated cattle.     

Transmission of foot-and-mouth disease by vaccinated cattle following natural challenge

Cattle vaccinated with a conventional monovalent type O1 foot-and-mouth disease (FMD) vaccine were challenged between four and 21 days after vaccination by short-term exposure to homologous airborne virus produced by pigs. Transmission was then assessed by housing susceptible cattle with the vaccinated animals and testing and observing all the animals for signs of infection and clinical disease. All 18 cattle vaccinated three weeks before challenge resisted clinical disease and although four contracted subclinical infection, there was no transmission to susceptible cattle in contact. One of the two groups of cattle vaccinated two weeks previously transmitted subclinical infection, but not disease, to susceptible animals housed with them from day 0 after challenge. Subclinical infection was manifested by a transient viraemia which was not followed by a detectable circulating antibody response. Shorter periods (seven or four days) from vaccination to challenge resulted in transmission of disease from clinically normal vaccinated to in-contact animals in one of two experiments. The severe challenge presented by the diseased in-contact animals than overwhelmed the immunity of the vaccinated animals. The results indicate that during emergency vaccination programmes it is advisable to vaccinate all FMD-susceptible animals within the vaccination zone and that at the outer boundary of the zone vaccinated animals should be kept separated from unvaccinated animals for at least three weeks.     

Endurance of immunity against foot-and-mouth disease in cattle after three consecutive annual vaccinations

Protection against foot-and-mouth disease (FMD) and ability to transmit FMD virus to susceptible contact animals were studied in cattle vaccinated three times in annual field campaigns with the Dutch trivalent vaccine. Eighty vaccinated cattle and 16 susceptible controls were intranasally exposed to an aerosol containing a homologous FMD challenge virus (O1 BFS, A10 Holland or C1 Detmold) or a heterologous virus (A5 Modena or C1 Modena). The day after exposure, vaccinated cattle were stabled individually with an FMD-susceptible contact. All cattle challenged with an homologous virus strain at one year (20 head), at two years (10 head) and at three years (30 head) after the last vaccination were protected against the development of clinical signs of disease; one, zero and five cattle of these groups, respectively, transmitted virus to their contacts. In each group, approximately two out of three exposed cattle had virus-positive oropharyngeal fluid samples and seroconverted. The amount of virus recovered from probang samples increased with the time since the last vaccination. Mean antibody titres of cattle that had not been vaccinated for three consecutive years did not change significantly over the last two-year period. All 10 cattle challenged with the vaccine strain-related C1 Modena virus were protected against clinical disease, whereas three out of 10 challenged with the heterologous A5 Modena strain virus one year after the last vaccination contracted FMD and transmitted the virus. Five others (four in the C1 group and one in the A5 group) spread the virus to their contacts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of experimental bovine pneumonic pasteurellosis with an extract of Pasteurella haemolytica.

A total of 36 calves were used in three experiments to test the efficacy of a potassium thiocyanate extract of Pasteurella haemolytica in protecting against experimental pneumonia. In each of experiments A and B, 12 calves were divided into three equal groups. The first group was vaccinated with an aerosol of a potassium thiocyanate extract twice, two weeks apart; the second group was vaccinated subcutaneously once only with the same extract. The third group of calves in both experiments remained as unvaccinated controls. In experiment C, six calves were vaccinated intramuscularly and six were left as controls. Approximately one month after vaccination all calves were challenged with an aerosol of bovine herpesvirus 1 (isolate 108) followed in 4 d by an aerosol of P. haemolytica type A1 (the same strain from which the potassium thiocyanate extract had been made). Varying degrees of protection against subsequent development of experimental pneumonic pasteurellosis in cattle were seen in vaccinated calves as compared to control calves in these experiments. The results indicate that protection of cattle against pneumonic pasteurellosis may prove possible with a sub-cellular extract of P. haemolytica.     

An inactivated vaccine for the control of bluetongue virus serotype 16 infection in sheep in Italy

Because no suitable products are at the moment available to safely control the spread of BTV-16 in Europe, an inactivated vaccine was produced from the reference field isolate of bluetongue virus serotype 16. One group of six sheep was vaccinated subcutaneously with the inactivated vaccine twice, on days 0 and 28, whereas a second group of eight sheep was inoculated with saline solution and used as mock-vaccinated control animals. Seventy-eight days after the first vaccination, all sheep were inoculated subcutaneously with a suspension containing 10(6.3) TCID(50) of a virulent reference BTV-16 isolate. Apart from a transient inflammatory reaction at the injection site, no adverse effects were reported following vaccination. All vaccinated animals developed high titres (7.3-9.3log(2)(ED50%/50 microl)) of virus-specific neutralising antibodies and were resistant to challenge with BTV-16. Conversely, following challenge, control animals developed hyperthermia and long lasting high-titre viraemia.     

Canine infectious tracheobronchitis: effects of an intranasal live canine parainfluenza-Bordetella bronchiseptica vaccine on viral shedding and clinical tracheobronchitis (kennel cough)

A modified-live intranasal (IN) canine parainfluenza (CPI)-virus Bordetella bronchiseptica vaccine was evaluated in dogs for efficacy against laboratory-induced canine infectious tracheobronchitis. The comparative efficacies of IN and parenteral administrations of the CPI virus fraction were also evaluated. The frequency and duration of clinical tracheobronchitis, blood serum agglutination titer, humoral antibody response, and duration of CPI virus and B bronchiseptica shedding were measured. Group A dogs were vaccinated subcutaneously or IM with an experimental CPI vaccine and challenge exposed with CPI virus. Group B dogs were vaccinated IN with avirulent CPI virus-B bronchiseptica live antigens and challenge exposed with virulent CPI virus and virulent B bronchiseptica. The IN vaccination (group B) significantly reduced (P less than or equal to 0.001) the occurrence of clinical tracheobronchitis by 96%. The combined challenge exposure of virulent CPI and virulent B bronchiseptica produced a synergistic enhancement of the clinical signs of kennel cough. The percentage of days after challenge exposure that virus shedding was detected for controls equaled 70% as compared with 50% and only 1% for parenterally and IN vaccinated dogs, respectively. Isolation of virulent B bronchiseptica microorganisms was reduced 89% in dogs vaccinated IN compared to controls. The geometric mean humoral antibody titers to CPI virus after 2 parenteral vaccinations and 1 IN vaccination were 1:43 and 1:34, respectively.     

Immunoglobulins in cattle vaccinated with leptospiral bacterins.

The growth-inhibition test was used to detect specific antibodies against Leptospira interrogans serotype hardjo in isolated immunoglobulin (IgG and IgM) fractions of serums from cattle vaccinated with leptospiral bacterins. The growth-inhibiting antibodies were detected mainly in the IgG class. Agglutinated clumps also occurred with the IgM fraction. The serums collected from cattle 4 months after vaccination were negative in the microscopic agglutination test.     

Comparison of the efficacy of three commercial bacterins in preventing canine leptospirosis

Twenty-four specific pathogen-free beagles were randomly allocated into four groups (three vaccinated groups and one control group) and inoculated at nine and 12 weeks of age with one of three commercial inactivated Leptospira vaccines: A (Vanguard 7; Pfizer Santé Animale), B (Dohyvac 7L; Fort Dodge), and C (Nobivac DHPPi + Lepto; Intervet International); the control group received Nobivac DHPPi (Intervet International). Seven weeks after the second vaccination all the dogs were challenged with Leptospira interrogans serogroup canicola. All the vaccinated dogs developed a mild serological response (microscopic agglutination titres) after the booster vaccination. A significant serological response after the challenge was observed, particularly in the controls. The challenge induced fever and clinical disorders in the control group, whereas in the vaccinated groups the clinical signs were mild. Blood cultures became positive in all control dogs, and in one of six dogs vaccinated with vaccine A and two of four dogs vaccinated with vaccine B; none of the six dogs vaccinated with vaccine C was leptospiraemic at any stage of the experiment. Urine cultures were positive in all the control dogs two weeks after the challenge. One of six dogs vaccinated with vaccine A and two of four dogs vaccinated with vaccine B shed bacteria in their urine after the challenge, but none of the dogs vaccinated with vaccine C shed bacteria in their urine at any time during the experiment.