Vaccination against infectious bovine keratoconjunctivitis: protective efficacy and antibody response induced by pili of homologous and heterologous strains of Moraxella bovis

The protective effect of 2 Moraxella bovis pili vaccines against infectious bovine keratoconjunctivitis (IBK) experimentally induced by homologous or heterologous strain challenge with virulent, haemolytic M. bovis strain, Dal 2d, was measured in trials using weaned calves aged 3 to 7 months. Purified pili vaccines were prepared from haemolytic strain Dal 2d, (pilus serogroup IV), and haemolytic strain Epp 63, (pilus serogroup III). Calves were challenged by conjunctival instillation of 1 x 10(9) colony forming units of virulent M. bovis strain Dal 2d 14 days after the second of 2 subcutaneous doses of vaccine. Each consisted of 200 micrograms of pili in alum-oil adjuvant administered at an interval of 21 days. In trial 1 the level of protection against challenge with the homologous strain was 46.7% (p less than 0.01). Small, rapidly resolving lesions of IBK occurred in some vaccinates compared with a larger proportion of severe lesions that required treatment in non-vaccinated calves (p less than 0.025). In trial 2, the level of protection against IBK after exposure of vaccinates to the homologous Dal 2d strain was 72.7%, but no significant level of protection or reduction in the size and duration of lesions was apparent in similarly challenged calves vaccinated with Epp 63 pili when contrasted with susceptible, non-vaccinated controls. No marked reduction in the duration of infection with M. bovis Dal 2d following challenge resulted from vaccination with pili of either of the serogroups III or IV. Rising homologous serum IgG antibody titres to serogroups III and IV pili were recorded in response to vaccination with each antigen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental production of infectious bovine keratoconjunctivitis: comparison of serological and immunological responses using pili fractions of Moraxella bovis.

The effect of vaccinating cattle and mice on the development of keratoconjunctivitis was studied. Cattle were vaccinated with whole cells, disrupted cells and pili fractions of three strains of Moraxella bovis. Mice were vaccinated with pili fractions of three strains. The resistance of all vaccinated animals was challenged with virulent cultures of M. bovis. In an attempt to correlate the response seen after vaccination and challenge with a pili fraction of M. bovis, vaccinated cattle and mice were grouped on the basis of signs of disease manifested and compared on the basis of serological responses. Serum samples were tested for antibodies by a gel diffusion precipitin test. A greater number of the sera of resistant cattle had antibodies to the homologous pili antigen than those of vaccinated nonresistant cattle. Cattle vaccinated with disrupted cells were not resistant to infectious bovine kerato-conjuctivitis and their sera lacked antibodies against the pili antigens. Vaccinated mice were more resistant to infectious bovine kerato-conjuctivitis and their sera lacked antibodies against the pili antigens. Vaccinated mice were more resistant to challenge exposure by homologous than heterologous cultures. A greater number of the sera of resistant mice had antibodies to pili antigens than nonresistant mice.     

Effectiveness of two commercial infectious bovine keratoconjunctivitis vaccines

Two commercially available infectious bovine keratoconjunctivitis (IBK) vaccines were evaluated for their effectiveness in protecting cattle from disease caused by experimental challenge exposure and natural transmission of Moraxella bovis infections. The study was conducted as 2 experiments, using a total of 81 cattle that were culture-negative for M bovis prior to vaccination. In each experiment, young adult cattle were randomly allotted to 4 groups. Each calf in groups 1 and 2 was vaccinated according to the vaccine manufacturer's directions. Groups 3 and 4 were unvaccinated controls. Three weeks after the last vaccination, each calf in groups 1 and 3 was experimentally challenge exposed by dropping a suspension of viable cells of a virulent strain of M bovis directly onto the corneal surface of each eye. Calves in all 4 groups were then commingled in open pastures so that calves in groups 2 and 4 could be naturally exposed to the calves with experimentally induced infections. Each calf was examined for signs of ocular disease on a regular basis by 2 experienced clinicians who scored each eye for severity of disease on the basis of a prearranged scale. Neither clinician was aware of the vaccination or exposure status of the calf nor to which experimental group they belonged. Lacrimal secretions were collected regularly to determine the number of eyes in which the virulent organism became established. Moraxella bovis with bacterial cultural characteristics similar to those of the virulent strain placed in the eyes of groups 1 and 3 was cultured from greater than or equal to 83% of the eyes of calves in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological relationship between strains of Theileria annulata Dschunkowsky and Luhs 1904

The immunological relationship between the Ludhiana and Hissar strains, and between the Uruli-Kanchan, Bangalore and Jaipur strains of Theileria annulata was studied. Calves were immunised against the Ludhiana strain by the infection-treatment method, against the Uruli-Kanchan strain by the infection-treatment method or by untreated low-grade infection and against the Jaipur strain by untreated low-grade infection. After 45 days, groups of immune calves and susceptible controls were challenged with 10-tick equivalent stabilates. The ensuing host responses, body temperature, swelling of the regional lymph node, appearance of schizonts in the regional lymph node and piroplasms in blood and mortality, were studied. All five strains proved very virulent and produced severe disease in susceptible calves. Immunisation with the Ludhiana, Uruli-Kanchan and Jaipur strains conferred absolute protection against severe homologous challenges. Immunisation with the Ludhiana and Uruli-Kanchan strains conferred substantial protection against heterologous challenges with the Hissar strain, and the Bangalore and Jaipur strains, respectively. Immunisation with the Uruli-Kanchan strain gave less protection against heterologous challenge with the Jaipur strain and vice versa as some of the challenged calves showed slight swelling of the regional lymph node, two had fever, all exhibited a low-grade parasitaemia and four developed anaemia.     

Intramuscular vaccination of young calves with a Salmonella Dublin metabolic-drift mutant provides superior protection to oral delivery

In homologous and heterologous challenge trials using calves 相似文献   

A comparison in calves of the antigenicity of three strains of bovid herpesvirus 2.

Three strains of bovid herpesvirus 2, viz. Allerton, bovine mammillitis and 69/1LO were used to infect calves intradermally. Twenty-eight days later the immunity of the calves was challenged by intravenous injection of a homologous or heterologous strain. Challenge control calves developed a fever (greater than 40 degrees C) lasting several days and widespread skin lesions which varied with the strain. Homologous challenge of the primary infection produced neither skin lesions nor febrile response, except in one calf in which fever was noted on one day. Heterologous challenge did not cause skin lesions but fever occurred in 8/12 calves. In particular Allerton virus failed to protect completely against heterologous challenge. Despite minor differences evident in these experiments, it is recommended that these isolates should be considered as strains of the same virus--bovid herpesvirus 2.     

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.     

Immunogenicity of a Moraxella bovis bacterin containing attachment and cornea-degrading enzyme antigens

An adjuvanted Moraxella bovis bacterin containing attachment antigens and cornea-degrading enzyme antigens protected cattle from infectious bovine keratoconjunctivitis (IBK) when experimentally challenged with homologous and heterologous challenge cultures of M. bovis. This bacterin also protected cattle against field exposure to M. bovis. Transmission electron microscopy and fluorescein labeled anti-M. bovis pili antiserum showed pili on the M. bovis bacterin strain. Scanning electron microscopy demonstrated a fibrillar glycocalyx. The bacterin strain of M. bovis, but not all strains of M. bovis, destroyed bovine corneal cell monolayers in vitro. Bovine corneal cells began to separate from each other within 5 min after M. bovis organisms were added and adhered to the cell monolayers. Moraxella bovis organisms remained attached to the disintegrating cells as the cell membrane separated and was digested. Vaccination stimulated bacterial agglutination antibodies. However, protection against experimental challenge was more closely related to the cornea-degrading enzyme content of the experimental bacterins. Twenty-two of 29 cattle (76%) vaccinated with bacterins containing a relative enzyme activity (REA) greater than 0.4 were protected in a rigorous challenge of immunity test. Only 1 of 21 non-vaccinated calves (5%) was free of IBK. Ninety-two percent (24/26) of calves vaccinated with a bacterin containing a REA greater than 0.29 remained free of IBK following field exposure, whereas 47% (8/17) non-vaccinated calves developed IBK. Only 8 of 12 calves (67%) vaccinated with a bacterin containing a REA of 0.09 remained free of IBK. In a larger field efficacy test consisting of 32 herds in six states, the incidence of IBK in individual herds ranged from 0% to 55%. The overall rate of infection was 11.2%. Vaccination of calves with an M. bovis bacterin that contained a REA of 0.63 reduced the incidence of IBK from 11.2% (217/1931) in the non-vaccinated controls to 4.3% (66/1520) in cattle vaccinated once and to 3.1% (48/1536) in cattle vaccinated twice.     

Heterologous strain immunity in bovine babesiosis using a culture-derived soluble Babesia bovis immunogen

The cross-protective capacity of culture-derived soluble immunogens against heterologous Babesia bovis strains from different geographical locations of Latin America was examined. Susceptible yearling cattle were either immunized with immunogens derived from Venezuelan or Mexican strains, or were administered a multi-component immunogen containing antigens of the Australian, Mexican and Venezuelan strains. Cattle were challenged with virulent B. bovis organisms of the Argentinian, Colombian, Ecuadorean, Mexican and Venezuelan strains. The major parameters used to evaluate cross-protection were the following: presence, level and duration of parasitemia; maximal PCV reduction; level and duration of fever; determination of fibrinogen and cryofibrinogen; homologous and heterologous antibody levels; and net gains in body weight. Results showed good protection with a Venezuelan B. bovis immunogen after homologous and heterologous challenge exposures. A low degree of cross-immunity was observed when cattle vaccinated with the Mexican immunogen were challenged with each of the heterologous strains.     

IMMUNITY IN CATTLE TO BABESIA BOVIS AFTER SINGLE INFECTIONS WITH PARASITES OF VARIOUS ORIGIN

Sixty calves, 3 to 6 months old, were vaccinated once against Babesia bovis in groups of 10, by the following methods: (a) tick infestation; (b) inoculation of virulent parasites obtained from the tick-infested animals immediately after infection; (c) inoculation of the parasites used in (b) attenuated by passage through splenectomised calves; (d) inoculation of commercially-available, living, attenuated vaccine; (e) inoculation of virulent parasites obtained from the tick-infested animals in (a) one year after infection; (f) inoculation of the parasites used in (e) attenuated by passage. All vaccinated animals were maintained tick-free and were strongly immune to challenge with a heterologous strain of B. bovis approximately 4 years after vaccination. There was no difference in immunogenicity between any of the B. bovis populations.     

Comparative study of two strains of Bovid herpesvirus-4

Two strains of Bovid herepesvirus-4 (BHV-4), i.e. the prototype strain DN-599, obtained from a steer suffering of a respiratory disease, and the strain 85/BH 16TV, originated from a cow with vulvovaginitis, were compared in studies which included restriction endonuclease analysis, experimental infection and reciprocal cross protection tests. The restriction endonuclease analysis revealed that the resultant DNA patterns of the isolates were generally similar with only a difference in one fragment. The two strains were capable of causing respiratory tract infection in calves, even if they displayed a different level of virulence: the strain 85/BH 16TV being the most virulent while the strain DN-599 the least. The two viral strains were mutually protective in that the calves were generally found to be refractory to challenge inoculation with either the homologous or the heterologous virus. Finally, both viral strains failed to evoke the production of neutralizing antibody in the experimental calves.     

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.     

Progress in the development of tuberculosis vaccines for cattle and wildlife

Vaccination against bovine tuberculosis is likely to become an important disease control strategy in developing countries, which cannot afford a test and slaughter control programme, or in countries which have a wildlife reservoir of Mycobacterium bovis infection. In the past decade, considerable progress has been made in the development and evaluation of tuberculosis vaccines for cattle and for a range of wildlife maintenance hosts including possums, badgers, deer and African buffaloes. Experimental challenge systems have been established for the different target species and the resulting disease process has mimicked that seen in the field. In cattle, neonatal vaccination with BCG appeared to be more effective than vaccination of 6-month-old calves and in most situations no other vaccine has been shown to be better than BCG. However, prime-boost strategies involving combinations of BCG with a protein or DNA vaccine, to improve on BCG vaccination alone, have produced very encouraging results. Differential diagnostic tests have been developed using mycobacterial antigens that are only present in virulent M. bovis to differentiate between BCG-vaccinated and M. bovis-infected cattle. BCG vaccine has been shown to reduce the spread of tuberculous lesions in a range of wildlife species and a prototype oral bait delivery system has been developed. Prospects for the development of improved vaccines against bovine tuberculosis are promising and vaccination approaches could become very valuable in the control and eradication of bovine tuberculosis.     

The effect of dose, route and virulence of bovine herpesvirus 1 vaccine on experimental respiratory disease in cattle.

Three experiments were conducted with calves in which, following intramuscular or intranasal vaccination with virulent or attenuated bovine herpesvirus 1, calves were protected against bovine herpesvirus 1 -- Pasteurella haemolytica challenge. Calves receiving low doses of vaccine had lower levels of antibody and greater evidence of virus replication upon challenge than those receiving higher doses. In contrast 11/13 unvaccinated controls had fibrino-purulent pneumonia following challenge. The immune response developed later in younger calves and those given low doses of vaccine. Neutralizing antibodies to bovine herpes-virus 1 were not found in nasal secretions, but were present in serum seven days after vaccination. Bovine herpesvirus 1 was isolated before challenge from nasal secretions of calves vaccinated intranasally or intramuscularly with virulent virus but not those vaccinated intramuscularly with vaccine virus. It was concluded that both routes of vaccination with either virulent or attenuated bovine herpesvirus 1 provided protection from challenge with homologous or heterologous bovine herpesvirus 1 and that live vaccines should contain at least 10(3) plaque forming units/dose for effective immunization.     

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.     

A study of some biologic properties of Bovid herpesvirus-4.

This article summarizes the results of a study on several strains of Bovid herpesvirus-4 (BHV-4), isolated from cattle. The study had several objectives, namely, to verify (a) the disease-causing potential of the virus, (b) the possibility by BHV-4 to induce a latent infection in the natural host and (c) the entity of the relationships among strains of the virus isolated from different disease syndromes. The following data were obtained: (1) All strains tested were able to replicate in experimentally infected calves; however, only one strain (85/BH 16TV) caused an overt systemic disease. (2) The nervous system as well as the lymphoid structures appeared to be the target organs for replication of the virus. (3) BHV-4, like other herpesviruses, was able to establish latent infection in cattle. (4) When two strains of the virus, isolated from cattle affected by different disease syndromes, i.e. respiratory disease (strain DN-599) or vulvovaginitis (strain 85/BH 16TV), respectively, they resulted to be closely related to each other. In particular, they revealed a similar DNA pattern and both strains were able to cause respiratory disease in calves. Moreover, the two viral strains were mutually protective in that calves were generally found to be refractory to challenge inoculation with either the homologous or the heterologous virus. (5) All BHV-4 strains tested generally failed to evoke a significant production of neutralizing antibody in the experimental calves.     

Babesia bigemina: attenuation of an Uzbek isolate for immunization of cattle with live calf- or culture-derived parasites

The virulence of an Uzbek isolate of Babesia bigemina, obtained from infected Boophilus annulatus ticks from an endemic area in Uzbekistan, was attenuated for immunization of cattle with autochthonous calf- or culture-derived parasites in Uzbekistan. After four "slow passages" in vivo the virulence was reduced, as evidenced by the response of calves inoculated with an experimental live frozen vaccine produced from the following passage. The vaccine was safe and protective against homologous virulent challenge under laboratory conditions. The culture-derived experimental vaccine was produced from cultures initiated after 3 passages in vivo followed by 22 passages in vitro. The cultured parasites did not elicit any clinical sign, but inoculated calves seroconverted following vaccination and were protected against the virulent homologous challenge. Both calf- and culture-derived vaccines were safe for cattle grazing in an endemic area in Uzbekistan. Despite the high polymorphism of B. bigemina, as reported from various geographical regions, the Central Asian strain was attenuated similarly to those that form the basis of the existing live B. bigemina vaccines in other parts of the world.     

Attenuated live fowl cholera vaccine. I. Development of vaccine strain M3G of Pasteurella multocida

A live cholera vaccine was developed from a virulent avian septicemia strain of Pasteurella multocida serotype 1. The virulent parental strain was mutagenized with N-methyl-N'-nitro-N-nitroso guanidine. Mutants were selected that had either smaller colonies at 37 C or temperature sensitivity for growth at 41 C. Four small-colony mutants and 2 temperature-sensitive mutants were studied. All the mutants were avirulent for turkeys. Sixteen days after turkeys were vaccinated with each mutant, both the vaccinates and unvaccinated controls were challenge-exposed to virulent P. multocida of the homologous serotype and the heterologous serotype 3. Two of the small-colony mutant strains protected against both homologous and heterologous challenge. Suggested for a live cholera vaccine is P. multocida M3G, a small-colony-forming mutant, innocuous for both mice and turkeys and stable against reversion.     

Efficacy of tulathromycin in the treatment of bovine respiratory disease associated with induced Mycoplasma bovis infections in young dairy calves

The efficacy of tulathromycin in the treatment of bovine respiratory disease (BRD) due to Mycoplasma bovis was determined following experimental infection. Two highly pathogenic strains of M. bovis (with minimum inhibitory concentration values for tulathromycin of 1 and >64 microg/ml) were inoculated into 145 calves. Four days after inoculation, calves with clinical BRD were treated subcutaneously with saline or tulathromycin (2.5 mg/kg). Compared with saline, BRD-related withdrawals, peak rectal temperatures, and lung lesion scores were significantly lower for tulathromycin-treated calves (P < .01). Tulathromycin was highly effective in the treatment of BRD due to M. bovis in calves regardless of the minimum inhibitory concentration of the challenge strain (1 or >64 microg/ml).     

Immune control of Babesia bovis infection

Babesia bovis causes an acute and often fatal infection in adult cattle, which if resolved, leads to a state of persistent infection in otherwise clinically healthy cattle. Persistently infected cattle are generally resistant to reinfection with related parasite strains, and this resistance in the face of infection is termed concomitant immunity. Young animals are generally more resistant than adults to B. bovis infection, which is dependent on the spleen. Despite the discovery of B. bovis over a century ago, there are still no safe and effective vaccines that protect cattle against this most virulent of babesial pathogens. Immunodominant antigens identified by serological reactivity and dominant T-cell antigens have failed to protect cattle against challenge. This review describes the innate and acquired immune mechanisms that define resistance in young calves and correlate with the development of concomitant immunity in older cattle following recovery from clinical disease. The first sections will discuss the innate immune responses by peripheral blood- and spleen-derived macrophages in cattle induced by B. bovis merozoites and their products that limit parasite replication, and comparison of natural killer cell responses in the spleens of young (resistant) and adult (susceptible) cattle. Later sections will describe a proteomic approach to discover novel antigens, especially those recognized by immune CD4+ T lymphocytes. Because immunodominant antigens have failed to stimulate protective immunity, identification of subdominant antigens may prove to be important for effective vaccines. Identification of CD4+ T-cell immunogenic proteins and their epitopes, together with the MHC class II restricting elements, now makes possible the development of MHC class II tetramers and application of this technology to both quantify antigen-specific lymphocytes during infection and discover novel antigenic epitopes. Finally, with the imminent completion of the B. bovis genome-sequencing project, strategies using combined genomic and proteomic approaches to identify novel vaccine candidates will be reviewed. The availability of an annotated B. bovis genome will, for the first time, enable identification of non-immunodominant proteins that may stimulate protective immunity.