Foot-and-mouth disease. Challenge of cattle after multiple vaccinations

Four groups of six cattle were vaccinated from two to five times at 6 month intervals with two different trivalent FMD vaccines licensed in the given year. The FMDV type A strains in the vaccines designated A5F and A5B were closely related. Three months after the last vaccination the cattle were challenged by contact with animals inoculated with the original field strain A5B. The inoculated animals developed typical FMD symptoms with vesicles in the mouth and on the feet. Those cattle which had received vaccines that did not contain strain A5B also became severely sick, even after five vaccinations. Animals vaccinated twice with type B containing vaccine were also not completely protected. A safe protection can obviously only be achieved for fairly short periods of time if vaccine and challenge strain are homologous. It is proposed to change the rules of licensing, to speed up the procedure to vaccinate in cases of outbreaks. The need for further research, especially into improving vaccines, is stressed.     

Efficacy of an oral live vaccine for veterinary use against pseudotuberculosis

Pseudotuberculosis, an infection caused by the ubiquitous enteropathogenic bacterium Yersinia pseudotuberculosis, is a recurrent veterinary problem in livestock and zoo animals. The only vaccine currently available in zoos is Pseudovac (a mixture of killed strains of various serotypes), but its efficacy is not well established. We show here that Pseudovac does not protect guinea pigs against a severe Y. pseudotuberculosis infection. We thus evaluated the possibility of using a live attenuated Y. pseudotuberculosis strain (IP32680) as an oral vaccine against animal pseudotuberculosis. We report that IP32680 is avirulent for guinea pigs and induces a strong IgG response against various serotypes of Y. pseudotuberculosis. One and two oral inoculations of IP32680 provided 50% and 83% protection, respectively against a severe infection with a highly pathogenic strain. The avirulent Y. pseudotuberculosis IP32680 is therefore much more protective than Pseudovac and may represent a valuable oral vaccine against pseudotuberculosis in zoo animals.     

Comparative safety and efficacy of attenuated single-strain and multi-strain vaccines for porcine reproductive and respiratory syndrome

The objective of this study was to compare the efficacy and safety of single-strain and multi-strain vaccines for the prevention of the respiratory facet of porcine reproductive and respiratory syndrome. The study comprised six groups of pigs (A through F, eight pigs per group). At the beginning of the study (Day 0) Groups C and D were vaccinated with a single-strain vaccine, and Groups E and F were vaccinated with a multi-strain vaccine. The multi-strain vaccine contained five attenuated strains of PRRSV including the strain used as the single-strain vaccine. On Day 28 Groups B (nonvaccinated/challenged control), D, and F were challenged with a highly virulent field strain of PRRSV that was unrelated to any of the strains used for vaccination. Group A was kept as a nonvaccinated/nonchallenged control. On Day 42 all pigs were necropsied. Their lungs and lymph nodes were examined for virus-induced changes. Serum samples obtained at weekly intervals during the study and lung lavage fluids obtained at necropsy were tested for the presence and titer of PRRSV. Serum samples were also tested for antibody. The presence and severity of clinical signs and lesions were the primary means by which vaccine efficacy and safety were evaluated. Both vaccines provided a high level of protective immunity to challenge. However, appreciable lymph node enlargement in pigs vaccinated with multi-strain vaccine, with or without subsequent challenge, raised a question as to its safety. Collectively these results indicate that both single-strain and multi-strain attenuated PRRSV vaccines can be effective immunogens, but additional studies in regard to safety are needed before multi-strain vaccines can be recommended for routine field use.     

Studies of infectious laryngotracheitis vaccines: immunity in broilers

Broiler chickens were vaccinated at 18 days of age against infectious laryngotracheitis (ILT) using chicken-embryo-origin (CEO) and tissue-culture-origin (TCO) vaccines, each vaccine given either by drinking water, spray, or eyedrop. Controls were not vaccinated. The broilers were challenged 3 weeks later with virulent ILT virus (USDA challenge strain). Serum samples taken before challenge were analyzed by a virus neutralization (VN) test to determine titers due to vaccination. Both vaccines, regardless of route of administration, produced low VN titers, geometric mean titer (GMT) being less than 4.0 in all vaccinated groups. When administered by the same route, the CEO vaccine produced higher titers than the TCO vaccine. Titers following drinking-water or eyedrop administration of vaccines were higher than titers following spray vaccination. There was an inverse relationship between pre-challenge VN titers of groups of birds and the percentage of birds in the groups dying from ILT virus challenge. The drinking-water route of vaccination provided the most protection, while the spray provided the least.     

DNA sequence analysis of glycoprotein G gene of bovine ephemeral fever virus and development of a double oil emulsion vaccine against bovine ephemeral fever

The surface glycoprotein G is considered as the major neutralizing and protective antigen of bovine ephemeral fever virus (BEFV). Comparison of the deduced amino acid sequence of G protein of BEFV isolates during the period 1984-2004 outbreaks in Taiwan showed amino acid substitutions in the neutralizing epitopes. All the isolates differ markedly in the neutralizing epitope at the same amino acid positions compared to the currently available killed vaccine strain (Tn73). Tn88128 strain isolated in 1999 showed the maximum variability of 12 amino acids, 5 amino acid in the neutralization epitope and 7 apart from, respectively. Combinations of both Tn88128 (1999) and commercially available vaccine strain (Tn73) were developed and its safety was evaluated in mice, guinea pigs, calves, and pregnant cows. None of the animals showed any adverse effect or clinical signs. Calves were immunized with commercial vaccine (Tn73) and, combined vaccine (Tn73 and Tn88128), respectively, with adjuvants such as Al-gel and water-in-oil-in-water (w/o/w) oil and PBS alone and challenged with Tn88128 strains. Except PBS administered animals, all the vaccinated animals showed protective immune response. However, animals immunized with combined vaccine plus w/o/w adjuvant elicited stronger neutralization antibodies and long lasting immunity compared to other vaccines.     

A serological and biochemical study of new field isolates of foot-and-mouth disease virus type A in Peru, 1975 to 1981

Three foot-and-mouth disease virus type A isolates recovered from field outbreaks in the Department of San Martin, Peru, during the period 1975 to 1981 were compared with each other, and the South American vaccine strains A24 and A27, by complement fixation (CF), virus neutralization (VN) and polyacrylamide gel electrophoresis (PAGE). Complement fixation and VN tests gave comparable results distinguishing the field isolates from each other and from the vaccine strains. Analysis of the structural polypeptides by PAGE also showed clear differences between all the viruses examined. Samples from tissue culture passaged and mouse adapted strains of one of the field isolates gave identical patterns in PAGE, but differences were observed in the polypeptide pattern of the A24/BRA/55 strain and the Peru vaccine strain, which were serologically indistinguishable. Results illustrate a continued antigenic variation in an endemic area where vaccination has been used; however, asymmetric serological reactions between the A24 vaccine strain and the most recent field isolate indicated that a vaccine incorporating A24 should still give adequate protection.     

Evaluation of different adjuvants for foot-and-mouth disease vaccine containing all the SAT serotypes

Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals that is primarily controlled by vaccination of susceptible animals and movement restrictions for animals and animal-derived products in South Africa. Vaccination using aluminium hydroxide gel-saponin (AS) adjuvanted vaccines containing the South African Territories (SAT) serotypes has been shown to be effective both in ensuring that disease does not spread from the endemic to the free zone and in controlling outbreaks in the free zone. Various vaccine formulations containing antigens derived from the SAT serotypes were tested in cattle that were challenged 1 year later. Both the AS and ISA 206B vaccines adjuvanted with saponin protected cattle against virulent virus challenge. The oil-based ISA 206B-adjuvanted vaccine with and without stimulators was evaluated in a field trial and both elicited antibody responses that lasted for 1 year. Furthermore, the ISA 206 adjuvanted FMD vaccine protected groups of cattle against homologous virus challenge at very low payloads, while pigs vaccinated with an emergency ISA 206B-based FMD vaccine containing the SAT 1 vaccine strains were protected against the heterologous SAT 1 outbreak strain.     

Preparation and use of an autogenous bacterin against infectious coryza in chickens

An experiment was conducted to determine the efficacy of an autogenous bacterin against infectious coryza from a local strain of Haemophilus paragallinarum in Morocco compared with a commercial vaccine. Hens were vaccinated with a single dose or two doses of the bacterin at 15 and 18 weeks of age. Both the autogenous and the commercial vaccine conferred significant protection against experimental challenge (94% and 88%, respectively). A single dose was less protective with both vaccines.     

Protective effects of clostridium sordellii LT and HT toxoids against challenge with spores in guinea pigs

The protective effects of Clostridium sordellii lethal toxin (LT) and hemorrhagic toxin (HT) toxoids against challenge with spores in guinea pigs were investigated. Purified LT and partially purified HT were obtained from the culture supernatant of C. sordellii strain 3703, and then were treated with formalin to make toxoids. LT. HT and combined LT and HT (LT/HT) toxoid vaccines were prepared by mixing each toxoid with an aluminum phosphate gel as adjuvant. Guinea pigs immunized twice with the respective toxoid vaccines were challenged with spores of strains 3703 or KZ1047. The latter strain does not produce HT. LT toxoid vaccine conferred protection against challenge with strain KZ1047, but not strain 3703, in guinea pigs. All guinea pigs immunized with HT toxoid vaccine died after challenge with spores of either strain. LT/HT toxoid vaccine gave complete protection against challenge with spores of strains 3703 and KZ1047 to guinea pigs. These results suggest that not only LT toxoid, but also HT toxoid, are essential protective antigens of C. sordellii.     

The protective efficacy of pili from different strains of Moraxella bovis within the same serogroup against infectious bovine keratoconjunctivitis.

Three groups of ten calves were each immunised with a total of 400 micrograms pili prepared from three separate strains of Moraxella bovis in Alhydrogel-oil adjuvant as two divided, equal doses 21 days apart. Groups 1 and 2 each received a monovalent vaccine made from strain 4L and S276R respectively, which belonged to pili serogroup A. Group 3 received vaccine made from pili of strain Maff1, belonging to serogroup F. A further group of ten calves served as non-vaccinated controls. Calves in groups 1 and 2 had developed serogroup A-specific antibody and those in group 3 developed serogroup F-specific antibody, and some evidence of cross-reacting antibody was also detected when measured by an agglutination test using formalin-killed piliated cells of serogroup A strain 4L. Although antibody titres measured against purified pili by ELISA were highest with homologous serogroup antigens, cross-reactive titres to shared epitopes of M. bovis pili were also detected by this method. Ocular challenge of the 40 calves with virulent M. bovis of serogroup A strain S276R was carried out 14 days after the second vaccine dose. All non-vaccinated calves developed infectious bovine keratoconjunctivitis (IBK). The percentage protection in groups 1 (strain 4L) and 2 (strain S276R) was 60% and 80% respectively (P less than 0.05), with mean lesion scores of 0.7 and 0.3 out of a possible 6.0. The percentage protection of calves in group 3 (strain Maff1) was only 30%, with a mean lesion score of 1.4 compared with 2.2 for non-vaccinated controls. The present findings, together with other evidence indicating that immunity to IBK is serogroup-specific, suggest that inclusion of pili from one representative strain from each of the seven Australian and British serogroups in a polyvalent, subunit vaccine should effectively protect the majority of cattle against IBK caused by most field strains of M. bovis encountered in Australia and the United Kingdom.     

Rapid methodology for antigenic profiling of FMDV field strains and for the control of identity, purity and viral integrity in commercial virus vaccines using monoclonal antibodies

Monoclonal antibodies (MAbs) developed against different foot-and-mouth disease virus (FMDV) vaccine strains were extensively used to study any possible antigenic variations during vaccine production in Argentine facilities. Additionally, a typing ELISA using strain specific MAbs was developed to detect potential cross contaminations among FMDV strains in master and working seeds with high specificity and sensitivity and to confirm strains identity in formulated vaccines. This assay was carried out for the South American strains currently in use in production facilities in Argentina (A24/Cruzeiro, A/Argentina/01, O1/Campos and C3/Indaial) and for the strain O/Taiwan, produced only for export to Asia. These non-cross reactive MAbs were also used to analyze the integrity of viral particles belonging to each one of the individual strains, following isolation of 140S virions by means of sucrose density gradients from the aqueous phase of commercial polyvalent vaccines. Antigenic profiles were defined for FMDV reference strains using panels of MAbs, and a coefficient of correlation of reactivity with these panels was calculated to establish consistent identity upon serial passages of master and production seeds. A comparison of vaccine and field strain antigenic profiles performed using coefficients of correlation allowed the rapid identification of two main groups of serotype A viruses collected during the last FMD epidemic in Argentina, whose reactivity matched closely to A/Argentina/2000 and A/Argentina/2001 strains.     

VACCINATION AGAINST EXPERIMENTAL STAPHYLOCOCCOSIS IN SHEEP - OBSERVATIONS ON BACTERIOLOGY AND PATHOLOGY FOLLOWING CHALLENGE

Sheep were vaccinated with a killed Staphylococcus aureus vaccine (2 doses) which had been cultured in vitro (Group 1), a killed S. aureus vaccine (2 doses) cultured in vivo (Group 2) or a single dose of a live vaccine (Group 3). Other sheep were used as non-vaccinated controls. All sheep were challenged by intravenous injection of 2.6 x 10(11) washed, viable S. aureus organisms, the vaccinated animals being given the challenge inoculum at various intervals after vaccination. The control sheep survived for 29h (mean) after challenge. Animals given killed vaccines survived longer, (particularly Group 2) if challenged less than 40 days post-vaccination, compared with those challenged more than 40 days post-vaccination. Animals in Group 3 survived longer if challenged after 40 days post-vaccination than those in Groups 1 or 2. There were no significant differences between the treatment groups for numbers of S. aureus recovered from blood in the 3h period following challenge. Histological and bacteriological evidence showed that the kidneys were more severely affected by the challenge inoculum than heart, spleen, liver or lungs. The kidneys showed both toxigenic and lymphoreticular reactions and large numbers of staphylococci were recovered more reliably from kidneys than other organs.     

Guinea pig protection test as indicator of potency of oil emulsion foot-and-mouth disease vaccines

A vaccine potency test is described involving virus challenge to six groups of 10 guinea pigs at five weeks after vaccination. Sixteen oil emulsion foot-and-mouth disease vaccines were so tested and nine retested after storage at 4 degrees C for up to 28.3 months. The results were compared with those of the routinely used oil emulsion vaccine potency test (protection afforded to eight pigs challenged 21 days after vaccination). When guinea pig estimates of 3 log2 PD50 or more were obtained, then, with one exception, the batches protected all or almost all pigs from challenge, but when the guinea pig estimates were less than 1 log2 PD50, the vaccines failed to protect five out of eight pigs. The sensitivity and reproducibility of the guinea pig method, established by repeated tests on two vaccine batches, seemed acceptable. The results suggested that guinea pig estimates might provide a suitable substitute for pig challenge potency tests because they reflected the potency of the vaccines, were likely to involve smaller standard errors and caused less discomfort to animals.     

Extensive antigenic and genetic variation among foot-and-mouth disease type A viruses isolated from the 1994 and 1995 foci in S?o Paulo, Brazil.

Nine foot-and-mouth disease virus (FMDV) type A isolates recovered from the field FMD foci in S?o Paulo State, Brazil, during 1994 and 1995 (a period preceding the last reported focus of FMD in 1996 in this state) were compared among themselves and with the reference vaccine strain A(24)Cruzeiro. The techniques used were sandwich ELISA, virus neutralization (VN), polyacrylamide gel electrophoresis (PAGE) of the structural polypeptides and direct sequencing of the VP1-coding region (1D gene). Results of VN were recorded as serological relationships "R" and those from ELISA were expressed as percentage of the homologous reaction "r". ELISA and VN gave comparable results (correlation coefficient, 0.936) allowing assignment of these field viruses to four groups which were distinct from the A(24)Cruzeiro strain. PAGE and 1D nucleotide sequencing were also able to distinguish between these viruses. The high level of genetic and antigenic variation found when comparing the A(24)Cruzeiro vaccine strain and type A strains recovered from the last identified foci of FMD came from a formerly endemic area where vaccination with polyvalent vaccines (O(1)Campos, A(24)Cruzeiro and C(3)Indaial) had been extensively applied. The similarity between the results of the serological and genetic analyses suggest that the antigenic differences found are mainly located in the 1D protein.     

Evaluation of three experimental bovine viral diarrhea virus killed vaccines adjuvanted with combinations of Quil A cholesterol and dimethyldioctadecylammonium (DDA) bromide

Bovine viral diarrhea virus (BVDV) infections cause respiratory, reproductive, and enteric disease in cattle. Vaccination raises herd resistance and limits the spread of BVDV among cattle. Both killed and modified live vaccines against BVDV are available. While modified live vaccines elicit an immune response with a broader range and a longer duration of immunity, killed vaccines are considered to be safer. One way to improve the performance of killed vaccines is to develop new adjuvants. The goal of this research was evaluate new adjuvants, consisting of combinations of Quil A cholesterol and dimethyldioctadecylammonium (DDA) bromide, for use in killed vaccines. Responses to three novel killed vaccines, using combinations of Quil A and DDA as adjuvants, were compared to responses to a commercial modified live and a commercial killed vaccine. Vaccination response was monitored by measuring viral neutralizing antibodies (VN) levels and by response to challenge. All three novel vaccines were efficacious based on reduction in virus isolation, pyrexia, and depression. Compared to a commercial killed vaccine, the three novel vaccines elicited higher VN levels and reduced injection site inflammation.     

Effects of challenge with a virulent genotype II strain of porcine reproductive and respiratory syndrome virus on piglets vaccinated with an attenuated genotype I strain vaccine

Porcine reproductive and respiratory syndrome virus (PRRSV) is endemic in most parts of Asia, where genotype I and II strains of diverse virulence may coexist. This study evaluated the outcome of infection with a highly virulent Asian genotype II PRRSV isolate in piglets vaccinated with a genotype I vaccine. Twenty-one 3-week-old piglets were divided in three groups: Pigs in group V (n=8) were vaccinated with an attenuated genotype I commercial PRRSV vaccine, while pigs in group U (n=8) and a control group (group C; n=5) were unvaccinated; 6 weeks later, pigs in groups V and U were challenged intranasally with a highly virulent strain of genotype II PRRSV (1×10(5) 50% tissue culture infectious doses/mL), while pigs in group C received a placebo. Over a period of 21 days after challenge, vaccinated pigs had significantly lower mortality (0/8 versus 2/8), fewer days of fever, a lower frequency of catarrhal bronchopneumonia, higher weight gains (13.4 versus 6.6 kg) and lower levels of viraemia compared to unvaccinated challenged pigs. Immunisation with a genotype I attenuated PRRSV vaccine provided partial protection against challenge with a highly virulent genotype II strain.     

Fundamental safety requirements in the use of live vaccine in food animals]

Live vaccines have a number of advantages over inactivated ones--above all in respect of the stimulation of cell-mediated immune reactions. Various live vaccines, based on viruses, bacteria, fungi or parasites, have been approved for use in Germany in animals used as a source of food. Safety requirements obviously play a more important role for live vaccines, both in vaccine development and in batch testing, than with inactivated vaccines. Vaccine strains isolated from tissue samples must be clearly distinguishable from field strains. The safety of overdoses and the spread of the vaccine strain in the immunized animals have to be investigated, as well as shedding of the vaccine strain and its safety in non-target species. Any impact of a live vaccine strain on humans and the environment must be assessed. Live vaccines will remain an important research field in the long term, with efforts focused on developing deletion mutants and vector vaccines.     

Feline leukaemia virus: a review of immunity and vaccination

The availability of feline leukaemia virus (FeLV) vaccines has added a new and important dimension to the control of this infectious agent. FeLV vaccination is a controversial issue, however, partly because of differences in the formulation between the current products, partly because of conflicting claims by vaccine manufacturers and partly because experimental trials have shown that none of the vaccines provides 100 per cent protection against infection. This paper reviews the role of the immune response in determining the outcome following exposure to FeLV and describes the importance of FeLV subgroups. The five commercial FeLV vaccines currently available in the USA and Europe are described and the published literature on efficacy studies is summarised. However, these efficacy studies are often difficult to interpret for various reasons, including the small numbers of animals used; differences in challenge methods, vaccine strains and vaccine dose employed; and differences in postchallenge monitoring protocols.     

Infectious bursal disease virus variant from commercial Leghorn pullets

An infectious bursal disease virus (IBDV) was isolated from 39-to-43-day-old commercial leghorn pullets suspected of having infectious bursal disease (IBD). These chickens had been vaccinated with a commercial live IBDV vaccine at 28 and 35 days of age. An isolate designated IN was recovered using specific-pathogen-free (SPF) chickens and the BGM-70 established cell line. Experimental studies using SPF chickens vaccinated with either inactivated vaccines made from the vaccine strain used in the problem flock or a standard-type vaccine indicated no protection against the IN isolate. However, two variants and another standard-type vaccine induced protection against the IN isolate. Cross-neutralization tests indicated that the IN isolate differed antigenically from commercial vaccine strains and was related to the variant IBDV strains recently isolated from broilers. To our knowledge, this is the first report of a variant IBDV recovered from commercial layer chickens in the United States.     

Reduction of economic losses caused by mycoplasmal pneumonia of pigs by vaccination with Respisure and by Tiamutin treatment

The possibilities and economic benefits of controlling mycoplasmal pneumonia of pigs caused by Mycoplasma hyopneumoniae by immunisation with Respisure and by Tiamutin treatment were studied. The experiment was carried out in a herd comprising 1000 sows which was free of PRRS, Aujeszky's disease, swine dysentery and leptospirosis, and the prevalence of mycoplasmal pneumonia was low because the farm had recently been restocked. Groups C1 and C2 served as untreated controls, while Groups R1 and R2 received a prestarter diet containing 100 ppm Tiamutin from the time of weaning. Piglets of Group R1 were vaccinated with Respisure vaccine once on day 69, while those of Group R2 twice, on days 65 and 80. Piglets of Groups ST1 and ST2 were fed 100 ppm Tiamutin in the diet for 7 days at the time of weaning and then at 4 months of age, while pigs of Group ST2 received such treatment also in the 6th month of life. The efficacy of treatment was analysed on the basis of the number of animals that died, were emergency slaughtered or were retarded in growth in the different groups, the body weight of animals at weaning, at 94 and 148 days of age and at the time of slaughter, their daily body weight gain, the lung lesions found in animals slaughtered from the different groups, the costs of medication and vaccination, and the cost-benefit calculations of the results. The mortality and emergency slaughter rate was 2.88% and 4.62% in Groups ST2 and ST1, respectively, 4.23% and 4.62% in Groups R2 and R1, respectively, and 8.39% and 9.44% in the control groups (C2 and C1, respectively). The rate of growth retardation was 0.48% and 2.12% in Groups R1 and R2, respectively, 1.59% and 3.46% in Groups ST1 and ST2, respectively, as compared to 8.03% and 6.55% in the control groups (C1 and C2, respectively). The severity score of lung lesions was 1.82 and 1.46 in Groups R1 and R2, 2.18 and 2.93 in Groups ST1 and ST2, and 3.83 and 4.02 in the control groups C1 and C2, respectively. The mean finishing weight of pigs was 102.4-107.8 kg and 95.2-106.6 kg in the treated groups and 94.5-98.6 kg in the control groups. The classification of pigs according to the EUROP categories showed a shift to the E and U categories in the treated groups. The average feed cost per one kg of liveweight was 77.89-82.64 Forints in the treated groups and 85.66 Forints in the control groups.