Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the evaluation of Marek's disease virus-induced immunosuppression in chickens

Antigen-specific lymphoproliferative responses were examined in chickens following immunization with tetanus toxoid (Ttx). The immune competence of chickens was assessed by mitogen assay utilizing phytohemagglutinin (PHA)-stimulation and Ttx-specific antigen proliferation assay (Ttx-APA). Immune spleen cells but not peripheral blood leucocytes demonstrated specific proliferation following stimulation in vitro in a Ttx-APA. In this study, we examined firstly the effects of Marek's disease (MD)-associated immunosuppression on specific immune responses. The humoral and cell-mediated immune responses were monitored by enzyme-linked immunosorbent assay (ELISA) and Ttx-APA, respectively. Secondly, we examined if vaccination against MD using a conventional herpesvirus of turkeys (HVT) vaccine and two recombinant HVT (rHVT) vaccines would affect the development of Ttx-specific immune responses. The rHVT vaccines used in this study included two constructs: one expressing both Newcastle disease virus (NDV) and MD virus (MDV) genes (HVT/NDV/MDV), and another expressing only MDV genes (HVT/MDV). The mitogenic responses of spleen cells of the vaccinated chickens were inconsistent allowing no definitive conclusions about vaccinal immunosuppression. The results of the Ttx-APA indicated that Ttx-specific lymphoproliferative responses provide a meaningful measure of immunosuppression. The MDV-induced immunosuppression resulted in the inhibition of Ttx-specific lymphoproliferation in vitro. Both HVT and rHVT vaccines were not immunosuppressive as indicated by the development of normal Ttx-specific lymphoproliferative responses in chickens. These results indicate that vaccination against MD results not only in the prevention of tumor formation but also protection from possible virus-induced immunosuppression.     

Onset of protective immunity in chicks after vaccination with a recombinant herpesvirus of turkeys vaccine expressing Newcastle disease virus fusion and hemagglutinin-neuraminidase antigens

The onset of protective immunity from lethal Newcastle disease virus (NDV) challenge of chicks was determined after vaccination with a recombinant herpes virus of turkeys (HVT) expressing the fusion and hemagglutinin-neuraminidase proteins of NDV. One-day-old specific-pathogen-free chicks devoid of maternal antibodies to NDV were vaccinated with 130 to 3300 plaque forming units of HVT (depending on the trial) and then challenged at 4, 7, 10, and 14 days postvaccination (DPV) with a neurotropic velogenic strain of NDV (GB Texas). The recombinant vaccine afforded 0%, 35-75%, 85%, and 94-100% protection when the vaccinated birds were challenged at 4, 7, 10, and 14 DPV, respectively. In all trials, challenge caused 100% mortality in unvaccinated control chicks. Newcastle disease virus was reisolated from the lung, liver, spleen, and brain of birds dying in all trials regardless of vaccine dosage or time of challenge, except when challenge occurred at 14 DPV.     

Vaccination with glutaraldehyde-fixed bovine respiratory syncytial virus (BRSV)-infected cells stimulates a better immune response in lambs than vaccination with heat-inactivated cell-free BRSV

The lamb model was used to investigate the possible protective effects of vaccination with inactivated viral antigens against experimental infection with bovine respiratory syncytial virus. Two groups of eight lambs were vaccinated with either glutaraldehyde-inactivated cell-associated virus or heat-inactivated cell-free virus and subsequently challenged with live virus, along with a group of naive lambs. The virus was shed for significantly longer periods, and the virus titres in nasal secretions were significantly higher in the group of naive lambs than in the two groups of vaccinated lambs. The period of virus-shedding in nasal secretions and virus titres was significantly lower (p < 0.01) in the group of lambs immunized with the cell-associated preparation. The same antigen stimulated better cellular immune responses as measured by virus-specific cytotoxicity or by virus-specific lymphocyte proliferation. However, priming with inactivated vaccines had no significant effect on lymphocyte responses to phytohaemagglutinin, which was found to be significantly reduced (p < 0.01) following challenge with live virus.     

Immunogenic characterization of a tissue culture-derived vaccine that affords partial protection against avian coccidiosis

The immunogenicity of a tissue culture-derived vaccine generated from an Eimeria tenella-infected cell line in a serologically defined bird line, and the ability to confer protection against homologous challenge in young chicks was examined. The cell line, SB-CEV-1/F7, was infected with E. tenella sporozoites and the resulting 72-h postinfection cell-free supernatants were adjuvanted and used to immunize Leghorn chicks homozygous for the B19 haplotype. Peripheral blood and splenic lymphocytes from these immunized birds proliferated in vitro in response to both sporozoite and SB-CEV-1/F7 tissue culture-derived parasite antigens. In addition, splenic immune lymphocytes obtained from birds previously exposed to E. tenella in vivo responded to these tissue culture-derived parasite antigens in vitro. To evaluate the efficacy of the vaccine, B19B19 chicks were vaccinated s.c. with adjuvanted 72-h postinfection cell-free supernatants or an ammonium sulfate precipitate derivative thereof, orally boosted, and then subjected to homologous parasite challenge at 10 d of age. The level of protection (body weight gain, cecal lesions) was assessed 6 d after challenge. Performance results from four battery trials demonstrated that vaccinated birds were significantly protected against weight loss compared to unimmunized, challenged controls. In addition, in two of the four trials, vaccinated birds were significantly protected against lesions. These results provide strong evidence that tissue culture-derived parasite antigens obtained from the E. tenella-infected SB-CEV-1/F7 cell line are immunogenic in birds and can provide partial protection against E. tenella clinical coccidiosis.     

Field evaluation of the safety and efficacy of a temperature-sensitive Mycoplasma synoviae live vaccine

Mycoplasma synoviae (MS) strain MS-H was used in three separate commercial flocks for large-scale evaluation of the safety and efficacy of the vaccine under commercial conditions. MS-H successfully colonized meat and layer-breeders vaccinated by eyedrop and persisted for up to 55 wk after vaccination. Restriction fragment length polymorphism analysis showed that MS-H was the only strain isolated from two vaccinated flocks. In a third flock, challenge with a wild-type MS occurred, and this strain was isolated from both vaccinated and unvaccinated birds. Vertical transmission of MS-H was investigated by culturing pipped embryos and testing broiler progeny for MS antibody at processing (56 days old). No evidence of vertical transmission was detected. Lateral transmission of MS-H strain from vaccinated to unvaccinated birds occurred in one of the commercial flocks. Forty-one of 50 isolates of MS-H obtained from vaccinated flocks maintained their temperature-sensitive phenotype, but nine isolates showed a nontemperature-sensitive phenotype.     

Studies on genetic and vaccination-induced resistance of chickens to lymphoid tumor transplants 2. Transmissible lymphoid tumor of Olson

Transmissible lymphoid tumor (TLT) was inoculated in wing webs of five-week-old chickens of 6 strains. About half of the chickens of each strain had been vaccinated with turkey herpesvirus (HVT) one week before challenge in the wing web with TLT. Tumors which developed at the site of inoculation usually reached maximum size within 2 weeks and then regressed. In some chickens, however, tumors developed in visceral organs and caused death in the 2nd through 5th weeks postinoculation. Comparisons among strains of chickens in Expt. 1 revealed no differences in mortality. Vaccination with HVT reduced mortality and also the incidence of wing-web tumors (WWT) in all strains of chickens. A lymphoid leukosis virus and a Marek's disease (MD) virus of low virulence were detected in preparations of TLT, and it is suggested that the immunity induced by vaccination may have been directed against tumor antigens associated with MD virus.     

Major histocompatibility complex class I-associated vaccine protection from simian immunodeficiency virus-infected peripheral blood cells

To evaluate the effectiveness of vaccine protection from infected cells from another individual of the same species, vaccinated rhesus macaques (Macaca mulatta) were challenged with peripheral blood mononuclear cells from another animal diagnosed with acquired immune deficiency syndrome (AIDS). Half of the simian immunodeficiency virus (SIV)-vaccinated animals challenged were protected, whereas unprotected vaccinates progressed as rapidly to AIDS. Protection was unrelated to either total antibody titers to human cells, used in the production of the vaccine, to HLA antibodies or to virus neutralizing activity. However, analysis of the serotype of each animal revealed that all animals protected against cell-associated virus challenge were those which were SIV vaccinated and which shared a particular major histocompatibility complex (MHC) class I allele (Mamu-A26) with the donor of the infected cells. Cytotoxic T lymphocytes (CTL) specific for SIV envelope protein were detected in three of four protected animals vs. one of four unprotected animals, suggesting a possible role of MHC class I-restricted CTL in protection from infected blood cells. These findings have possible implications for the design of vaccines for intracellular pathogens such as human immunodeficiency virus (HIV).     

Marked increases in neuronal nitric oxide synthase (nNOS) mRNA and NADPH-diaphorase histostaining in adrenal cortex after immobilization stress in rats

The immunoprophylaxis of mycoplasmal pneumonia of swine (MPS) caused by Mycoplasma hypopneumoniae was investigated for the first time in fattening pigs in Croatia. The incidence of MPS was monitored in pigs weighing on average 27.5 kg (12 weeks old) after immunization with a M. hyopneumoniae vaccine. Of 350 pigs in each group, in the nonvaccinated group 55 animals (15.7%) were affected by pneumonia and 11 (3.1%) died of consequences of pneumonia, whereas in the vaccinated group 20 pigs (5.7%) were affected by pneumonia without any death due to the infection. In the nonvaccinated group 44% more pigs were individually treated with antibiotic, and these animals received in-feed therapy for more than 1/4 of the fattening period. Vaccinated pigs gained weight faster, at the rate of 0.745 kg/day (or 82 g/day more) than control animals. The mean score of lung lesions due to M. hyopneumoniae was 10.51 in the control pigs and only 0.54 in the vaccinated animals. The total tissue alterations on lungs due to M. hyopneumoniae, Pasteurella multocida and/or Actinobacillus pleuropneumoniae expressed as the mean-score were 13.21 in the control group and 2.98 in the vaccinated group. According to the results of evaluation of the M. hyopneumoniae vaccine in the field, the vaccine appeared to provide an adequate immunity in fattening pigs but was less effective when administered to younger pigs at 1-3 weeks of age.     

Rubella vaccination of schoolgirls: factors affecting vaccine uptake

In a national sample of 16-year-old girls who were aged 12 when the rubella vaccine programme was implemented in 1970, 71% were reported to have received rubella vaccine. There was a high regional disparity in the uptake of rubella vaccine: 81% of girls living in Scotland had been vaccinated but only 61% of girls living in Wales. Similarly there was a difference in reported vaccine uptake according to the family social background, the lowest proportion vaccinated came from professional and unskilled manual families. Girls attending independent schools also had a lower vaccine uptake than girls in schools maintained by the local educational authorities. If rubella immunisation is to be effective uptake of vaccine must increase to almost 100%.     

Vaccine protection by a triple deletion mutant of simian immunodeficiency virus

Twelve rhesus monkeys were vaccinated with SIVmac316 delta nef (lacking nef sequences), and 12 were vaccinated with SIVmac239 delta3 (lacking nef, vpr, and upstream sequences in U3). SIVmac316 and SIVmac239 differ by only eight amino acids in the envelope; these changes render SIVmac316 highly competent for replication in macrophages. Seventeen of the animals developed persistent infections with the vaccine viruses. Seven of the 24 vaccinated animals, however, developed infections that were apparently transient in nature. Six of these seven yielded virus from peripheral blood when tested at weeks 2 and/or 3, three of the seven had transient antibody responses, but none of the seven had persisting antibody responses. The 24 monkeys were challenged in groups of four with 10 rhesus monkey infectious doses of wild-type, pathogenic SIVmac251 at weeks 8, 20, and 79 following receipt of vaccine. None of the seven with apparently transient infections with vaccine virus were protected upon subsequent challenge. Analysis of cell-associated viral loads, CD4+ cell counts, and viral gene sequences present in peripheral blood in the remainder of the monkeys following challenge allowed a number of conclusions. (i) There was a trend toward increased protection with length of time of vaccination. (ii) Solid vaccine protection was achieved by 79 weeks with the highly attenuated SIV239 delta3. (iii) Solid long-term protection was achieved in at least two animals in the absence of complete sterilizing immunity. (iv) Genetic backbone appeared to influence protective capacity; animals vaccinated with SIV239 delta3 were better protected than animals receiving SIV316 delta nef. This better protection correlated with increased levels of the replicating vaccine strain. (v) The titer of virus-neutralizing activity in serum on the day of challenge correlated with protection when measured against a primary stock of SIVmac251 but not when measured against a laboratory-passaged stock. The level of binding antibodies to whole virus by enzyme-linked immunosorbent assay also correlated with protection.     

Kinetic analysis of T cells and antibody production in chickens infected with Marek's disease virus

In chickens inoculated with a Marek's disease (MD) vaccine and subsequently with virulent MD virus (MDV), CD4+ T cell population was drastically decreased following a transient increase at 21 days after hatching (16 days after MDV infection). To elucidate the immune response after the decrease of CD4+ T cell population, the antibody production against sheep red blood cells (SRBC) was examined in these chickens. Chickens challenged with a virulent MDV after MD vaccination produced lower titers, of anti-SRBC antibody than untreated control chickens. Antibody production against SRBC was also lowered in vaccinated chickens or chickens challenged with a virulent MDV.     

Development of effective living vaccines against bovine babesiosis--the longest field trial?

Between 1959 and 1996, research was performed to change a vaccine against babesiosis in Australia and to improve it as actual or threatened untoward field responses became apparent. The most significant change occurred in 1964 with the traditionally used carriers of Babesia being replaced as vaccine donors by acutely infected splenectomised calves. This ensured the infectivity of the vaccine and was fortuitously associated with a reduction in the virulence of Babesia bovis in vaccine. Since then, more than 27 million doses of highly infective vaccine have been supplied from the laboratory at Wacol near Brisbane. This vaccine reduced serious losses from babesiosis in vaccinated cattle in Australia to very low levels and has now gained acceptance worldwide. Research to ensure the continuing effectiveness of the vaccine has proved to be essential.     

Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines

This study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8) or SIVmac32H ISCOM vaccine (n = 8). Controls included animals vaccinated with measles virus in MDP adjuvant (n = 4) or ISCOM (n = 4) preparations. Of each group, half were challenged intravenously (IV) with ten MID50 of the cell-free SIVmac32H (11-88) SIV stock and half were challenged with ten MID50 of PBMCs from the SIVmac32H infected macaque 1XC. All SIV vaccinated animals challenged with the 11-88 cell free stock of SIVmac32H were protected, whereas only half of the SIV vaccinated monkeys receiving the same infectious dose of the 1XC cell stock were protected.     

Vaccine evaluation studies of replication-defective SIVsmB7

Non-infectious virus-like particles of SIVsmB7 that expresses env and gag gene products but are defective in pol and vpx/vpr were assessed for their ability to induce protective immunity against infection with pathogenic SIVsmE660 in rhesus macaques. Animals were immunized in three groups: group A was primed with cell-associated SIVsmB7 and boosted with cell-free SIVsmB7; group B was primed with cell-free SIVsmB7 and boosted with cell-free SIVsmB7 conjugated to iron oxide microbeads; group C was primed with cell-free SIVsmB7 mixed with Titer Max adjuvant and boosted with cell-free SIVsmB7 mixed with SAF-M adjuvant followed by secondary boosting with cell-free SIVsmB7 conjugated to microbeads. Animals were challenged intravenously with 20 animal infectious doses of SIVsmE660 grown in rhesus peripheral blood mononuclear cells 3 weeks after final boosting. All animals became infected as evidenced by quantitative virus cultivation. Sera from immunized animals contained low-titer antibodies by ELISA and low or undetectable neutralizing antibodies on the day of challenge but strong anamnestic antibody responses were observed following challenge. Interestingly, 2 of 3 animals in group A showed evidence of transient viremia and more stable CD4 counts following challenge as compared to the other immunized animals and to non-immunized controls. Thus, immunization with cell-associated SIVsmB7 did not provide sterilizing immunity against challenge with a highly pathogenic SIV strain but might have caused virus clearance later in infection.     

Epidemiological investigations on measles in unvaccinated and vaccinated children (author's transl)

A national study, with participation of 82 paediatricians, was carried out on 9472 children over medium observation periods of between 3.13 and 5.46 years with evaluation of the history of measles, incidence of complications and details of vaccination procedure performed. The protection rate of primary vaccination with live vaccine was 0.89, with split vaccine (3 times) 0.67 and after a combination of split vaccine (3 times) with live vaccine (9 to 12 months later) 0.94. Complications due to measles in unvaccinated children were found in 5.9% of cases. Measles complications after failure of vaccination were found in 2.9% and 2.8% of children vaccinated with live or split vaccine, respectively. No such complications were observed in children vaccinated with a combination of split and live vaccines.     

Restriction endonuclease profiles of orf virus isolates from the British Isles

A comparison of DNA profiles of representative isolates of orf virus, obtained using four different restriction endonucleases (RE), showed that the enzyme EcoRI could be used to discriminate between wild-type virus isolates and vaccine strains. The enzyme was used to compare the RE profiles of orf virus isolates from 43 outbreaks of orf that occurred in vaccinated flocks between 1988 and 1993; 21 outbreaks yielded wild-type virus, 10 yielded vaccine viruses, three produced both vaccine and wild-type viruses and no clear result was obtained from nine of the outbreaks. From the 21 outbreaks yielding wild-type viruses, 28 orf virus isolates had clear RE profiles and 15 distinct RE profiles were recorded. Usually only one virus type was associated with each outbreak but from two farms, two different wild-type viruses were recovered. No predominant genotype was identified, with four RE profile types being recovered for more than one outbreak. From the more severe form of orf involving the buccal cavities of lambs only wild-type viruses were recovered, with at least four different genotypes being represented.     

Identification and initial characterization of mSLK, a murine member of the STE20 family of kinases

Among 2099 uninfected subjects in phase I and II trials of candidate AIDS vaccines, 23 were diagnosed with intercurrent human immunodeficiency virus type 1 (HIV-1) infection. High-risk sexual exposures accounted for 17 infections, and intravenous drug use accounted for 6. Four subjects received placebo, 13 received a complete immunization schedule (> or = 3 injections), and 6 were partially immunized (< or = 2 injections). There was no significant difference between vaccine recipients and control groups in incidence of HIV-1 infection, virus load, CD4 lymphocyte count, or V3 loop amino acid sequence. In summary, 19 vaccinated subjects acquired HIV-1 infection during phase I and II trials, indicating that immunization with the products described is < 100% effective in preventing or rapidly clearing infection. Laboratory analysis suggested that vaccine-induced immune responses did not significantly affect the genotypic or phenotypic characteristics of transmitted virus or the early clinical course of HIV-1 infection.     

Protection by a commercial Arkansas-type infectious bronchitis virus vaccine against a field isolate of the same serotype

A late-breaking infectious bronchitis virus (IBV)-associated respiratory disease was a chronic problem in Georgia broilers in 1995. The predominant virus isolated from diseased birds was the Arkansas (Ark) type of IBV. Because broilers in Georgia are currently vaccinated with the Arkansas serotype, there was concern that a phenotypic and/or genotypic change had occurred in the field virus so it could break through immunity conferred by commercial vaccines. The purpose of this study was to determine if a commercially available vaccine for IBV as currently used in the field still protected broilers against those viruses. We obtained 108 1-day-old broilers from a commercial source and assigned them randomly to 12 groups. One-half of the groups of birds were vaccinated at 1 day of age and again at 18 days of age with commercially available B1/Mass/Ark vaccine. One-half of both vaccinated and nonvaccinated groups of birds were challenged at 35 and 42 days of age with a recent IBV Ark field isolate. Serologic titers were evaluated by enzyme-linked immunosorbent assay at time of challenge and at the end of the trial. A necropsy was performed on birds at 56 days and pathogenicity was assessed. Seroconversion was statistically significant in all birds exposed to vaccine or challenge by 56 days of age. Gross airsacculitis was significantly more severe in broilers challenged without prior exposure to vaccine.     

Serologic response to revaccination with two rubella vaccines

Three years after receiving rubella vaccine, 1,060 elementary school children living on the island of Maui, Hawaii, were revaccinated with either HPV-77 DE-5 or RA 27/3 rubella vaccine given subcutaneously or intranasally in order to compare the effectiveness of these two vaccines in raising antibody titers. RA 27/3 was the more effective booster vaccine, producing fourfold or greater titer rises in 20.1% of recipients, including 80% of children with hemagglutination-inhibiting antibody titers less than or equal to 1:40 at the time of revaccination, intranasal revaccination was not significantly more effective than subcutaneous revaccination, although it did elicit higher titers in children who responded. Responses differed according to the vaccine that children had received three years earlier. Because antibody titers have persisted in vaccinated children, routine administration of a second dose of rubella vaccine is not currently recommended.     

Novel methods for molecular dynamics simulations

HYPOTHESIS: Monovalent measles vaccine can be administered to children 6 to 11 months of age during an outbreak. Efficacy and effectiveness of this control measure still have to be assessed. METHODS: During and outbreak of measles, monovalent measles vaccine was administered as part of outbreak control to children aged 6 to 11 months. Active surveillance was used to detect cases of measles occurring during the following month. Children who did not develop measles were tested for measles antibody before their revaccination at 15 months of age. RESULTS: Of 81 children 6 to 11 months of age, 56 were vaccinated and two received immunoglobulins; the latter were excluded from the analysis. Measles occurred in 15 of the 79 children during and after the vaccination campaign, for an overall attack rate of 19%. The attack rate among unvaccinated children was 39% (9 of 23), compared with 11% (6 of 56) among those vaccinated (relative risk = 3.6, 95% confidence interval [CI] = 1.5 to 9.1). All of those who sustained measles in the vaccinated group developed the disease within 10 days after vaccination. The overall vaccine effectiveness was 73% (95% CI = 32% to 89%) when children were classified as vaccinated as soon as they were given measles vaccine. It rose to 96% (95% CI = 72% to 99%) when children were considered vaccinated 1 week postimmunization. Nineteen infants who were vaccinated and who did not develop measles during the outbreak were tested for measles antibody status at 15 months of age before revaccination. All had plaque reduction neutralizing antibody titers greater than 120. CONCLUSION: This study confirms that measles vaccination of infants aged 6 to 11 months is an effective intervention measure during measles outbreaks.