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Specificity of the Tumor-specific transplantation antigen induced by JC virus, a human polyomavirus.

The specificity of the tumor-specific transplantation antigen (TSTA) induced by JC virus was investigated by cross protection tests in weanling hamsters. Hamsters immunized with JC virus, BK virus, or SV40 were challenged 5 weeks later with known numbers of JC virus- or SV40-induced hamster tumor cells. Both the JC virus-immune and the SV40-immune hamsters showed resistance to challenge with homologous but not heterologous tumor cells, and the BK virus-immune hamsters were not resistant to either heterologous tumor cell. The TSTA induced by JC virus did not cross-react with that induced by SV40.

Animals↗

Protection against systemic infections with various Candida species elicited by vaccination with Candida albicans ribosomes.

This study investigated whether subcutaneous vaccination of mice with ribosomes from Candida albicans strain CBS 562 would also provide protection against infections by other isolates of Candida. Experiments with a total of 628 mice demonstrated that vaccination induced significant protection against heterologous C. albicans (serotypes A and B) and C. tropicalis isolates in terms of their 30 day survival rates. In all instances, however, protection was lower than that obtained against the homologous strain. In addition, a significant decrease in fungal colonization of the kidneys was found in immunized animals as compared to the non immunized controls. Cell-mediated immune responses against cytoplasmic extracts of the various fungi, as detected in vivo by the foot pad swelling test and in vitro by the lymphocyte transformation assay, were induced by the C. albicans ribosomal vaccination. The results show it is possible to induce cross protection to various Candida species by immunization with C. albicans ribosomes.

Animals↗

Serological and pathogenic characterization of Erysipelothrix rhusiopathiae isolates from tonsils of slaughter pigs in Indonesia.

Erysipelothrix rhusiopathiae was isolated from tonsils of 245 (35.7%) of 687 apparently healthy slaughter pigs in Indonesia during the period of June 1987 to February 1988. A total of 150 of the 245 E. rhusiopathiae isolated could be serotyped within the 22 recognized serotypes. Serotype 2 was most prevalent with 23.7%, followed by Serotypes 11, 12, 1a, 5 and 6 representing 7.3, 5.3, 4.9, 4.9 and 4.1% of the isolates, respectively. The nine other serotypes (Serotypes 1b, 3, 4, 8, 9, 10, 13, 19 and 22) combined to make up 11.0% of the isolates. Antibiotic-resistant strains were not found. Of 86 selected isolates belonging to various serotypes, 76 (88.4%) were highly virulent for mice (LD50 less than 10(3.0) colony-forming units). In swine, 40 (51.2%) of 78 isolates induced local or generalized urticarial lesions after intradermal inoculation, and the remaining 38 isolates induced no clinical signs. Of 76 isolates used for challenge in the cross-protection study, 29 (38.2%) killed greater than 40% of mice immunized with an erysipelas bacterin marketed in Indonesia. A tendency to be refractory to the bacterin-induced immunity was observed in some isolates of various serotypes, but this characteristic was not consistent.

Animals↗

Hemagglutinating activity and immunological properties of Haemophilus paragallinarum field isolates in Japan.

Four field isolates (S4, S10, S15, and S17) of Haemophilus paragallinarum were recovered from chickens affected with infectious coryza in widely separated regions of Japan. Their hemagglutinating (HA) activity and immunological properties were compared with those of strain 221 of serovar A/1 and strains Modesto and S1 of serovar C/2. When treated with potassium thiocyanate or hyaluronidase, all the isolates showed HA activity against formaldehyde-fixed chicken erythrocytes but not against fresh chicken erythrocytes. In the hemagglutination-inhibition (HI) test, the isolates cross-reacted with strains Modesto and S1 but not with strain 221. The immunological properties of these isolates, as determined by cross-protection tests, were similar to those of strain S1 and, to a lesser degree, strain Modesto, but not to strain 221. Our results indicated that the four field isolates belong to serovar C/2 and that the HI test is a suitable method for serotyping H. paragallinarum.

Animals↗

Fasciola hepatica: host responders and nonresponders to parasite glutathione S-transferase.

Fasciola hepatica glutathione S-transferase (FhGST) was isolated from adult worms by glutathione agarose affinity chromatography. SDS-PAGE shows three proteins of M(r) ranging from 29-27.8 kDa. Western immunoblot analyses using SDS-PAGE separated adult worm extracts and probed with a rabbit anti-FhGST antiserum reveal two bands in the same M(r) range. Mice and rabbits immunized with purified FhGST develop copious amounts of anti-FhGST antibodies. Moreover, antisera to F. hepatica adult worms and excretion-secretion products also react with FhGST. Cross-reactivity with schistosomes is evidenced in the reactivity with FhGST of anti-Schistosoma mansoni adult worm antisera and, to a lesser extent, antisera to S. mansoni-soluble egg antigens. The time of appearance of anti-FhGST antibodies in different species of animals infected with F. hepatica was determined. Sheep and a New Zealand white rabbit developed anti-FhGST antibodies detectable by ELISA as early as 2 weeks postexposure with F. hepatica. However, neither mice nor calves infected with F. hepatica developed antibodies to FhGST through the 5-10 weeks of infection tested. But mice infected with S. mansoni developed anti-FhGST cross-reacting antibodies by 6 weeks of infection. Calves immunized with a Fasciola/Schistosoma cross-reactive, cross-protective antigen complex in which a 12,000-kDa protein (Fh12) has been shown to contain immunoprophylactic activity, also developed antibodies to FhGST. Since FhGST is a novel potential vaccine, its protection-inducing capability in a multivalent vaccine combined with Fh12 clearly warrants study. In summary, it appears that hosts with fascioliasis are either responders to FhGST (rabbits, sheep) or nonresponders (mice, cattle), offering interesting models for studying the immune response.

Animals↗

Cross-reaction among four isolates of Theileria annulata from India.

A close identity in virulence and cross-protection of four isolates of Theileria annulata was observed when infection was produced in naive, crossbred (Bos taurus male X B. indicus female) male calves. The evidence that strains of T. annulata in India differ in virulence and immunogenicity is equivocal at present.

Animals↗

Intranasal immunization with formalin-inactivated virus vaccine induces a broad spectrum of heterosubtypic immunity against influenza A virus infection in mice.

It has been known that influenza A virus infection induces a cross-protective immunity against infection by viruses with different subtypes of viral envelope proteins, hemagglutinin (HA) and neuraminidase (NA). This heterosubtypic immunity is generally mediated by cytotoxic T lymphocytes (CTL) reactive to specific epitopes in the viral internal proteins, such as nucleoprotein and matrix protein. By contrast, immunization with inactivated virus antigens has been thought to be unable to generate heterosubtypic immunity, since inactivated antigens do not usually induce CTL responses. However, we show that intranasal immunization with formalin-inactivated intact virus, but not ether-split vaccines, induced a broad spectrum of heterosubtypic protective immunity in mice. The protection may be mediated by the mucosal immune response, most likely secretory IgA antibodies to the viral proteins. This approach may overcome limitations in the efficacy of inactivated influenza vaccines and confer potent immunity to humans against viruses with new pandemic potential.

Administration, Intranasal↗

Fasciola antigens as vaccines against fascioliasis and schistosomiasis.

Fascioliasis is an important trematode infection of herbivores worldwide with increasing evidence of prevalence as a disease of humans. Vaccination studies with purified native and recombinant Fasciola antigens suggest that this approach to diminished morbidity and mortality and reduced transmission is a realistic goal. Among the major potential vaccine candidates are fatty acid binding protein (FABP), cysteine (cathepsin) proteases, haemoglobulin, leucine aminopeptidase, and a saposin-like protein. In the case of Fasciola hepatica FABP, cross-reaction and cross-protection against Schistosoma mansoni is an important feature. In addition to protective effects with significant worm burden reductions, some vaccine candidates also have anti-fecundity (smaller flukes), anti-pathology (less liver lesions), and anti-embryonation effects. Optimism is tempered by the fact that fascioliasis in humans is an orphan disease and in need of governmental and foundation support.

Animals↗

Anti-Thy-1 treated and irradiated spleen cells from (BALB/c x C57Bl/6) F1 mice infected with Plasmodium chabaudi chabaudi can transfer protection into irradiated hosts.

The transfer of spleen cells from (BALB/c x C57Bl/6) F1 mice recovered from a Plasmodium chabaudi chabaudi AS infection into irradiated syngeneic recipients conferred protection. Neither elimination of Thy-1+ cells nor in vitro irradiation of immune cells before transfer affected protection while both anti-Thy-1 treatment and irradiation abolished the appearance of anti-P. c. chabaudi antibodies in the recipients. Superinfection of immune spleen cell donors did not improve their capability to transfer protection which was also unaffected by anti-Thy-1 treatment. The serum of mice after one infection was only marginally protective when transferred into irradiated recipients and a second infection improved the protective activity of serum which was not further improved by six infections. The co-transfer of immune serum and immune cells did not result in any synergistic effect. On the other hand, when P. c. chabaudi AS (BALB/c x C57Bl/6) F1 infected mice were challenged with a high dose of Plasmodium yoelii 17XL at crisis, the mice were unable to control the heterologous parasite. When mice were challenged with P. yoelii 17XL several weeks after infection with P. c. chabaudi AS, a good degree of cross-protection was observed.

Animals↗

Prospects for development of a vaccine against the West Nile virus.

Vaccination provides the ultimate measure for personal protection against West Nile disease. The development of a West Nile vaccine for humans is justified by the uncertainty surrounding the size and frequency of future epidemics. At least two companies (Acambis Inc. and Baxter/immuno) have initiated research and development on human vaccines. West Nile encephalitis has also emerged as a significant problem for the equine industry. One major veterinary vaccine manufacturer (Ft. Dodge) is developing formalin-inactivated and naked DNA vaccines. The advantages and disadvantages of formalin-inactivated whole virion vaccines, Japanese encephalitis vaccine for cross-protection, naked DNA, and live attenuated vaccines are described. A novel technology platform for live, attenuated recombinant vaccines (ChimeriVax) represents a promising approach for rapid development of a West Nile vaccine. This technology uses yellow fever 17D as a live vector for envelope genes of the West Nile virus. Infectious clone technology is used to replace the genes encoding the prM and E structural proteins of yellow fever 17D vaccine virus with the corresponding genes of West Nile virus. The resulting virion has the protein coat of West Nile, containing all antigenic determinants for neutralization and one or more epitopes for cytotoxic T lymphocytes. The genes encoding the nucleocapsid protein, nonstructural proteins, and untranslated terminal regions responsible for replication remain those of the original yellow fever 17D virus. The chimeric virus replicates in the host like yellow fever 17D but immunizes specifically against West Nile virus.

Animals↗

A formalin inactivated whole SIVmac vaccine in Ribi adjuvant protects against homologous and heterologous SIV challenge.

Eight monkeys were immunized at 0, 4, 9, and 18 weeks with a total of 2 mg of formalin inactivated SIVmac vaccine with Ribi adjuvant. Two weeks after the last booster four immunized monkeys and two controls were challenged with 10 MID50 of live homologous virus SIVmac, and the remaining four vaccinated animals along with two controls were challenged with the heterologous SIVsm strain. All eight vaccinated monkeys resisted the virus challenge, whereas all controls became infected. Three months after the first challenge the monkeys were rechallenged with the same virus strain, without further boosting. Two of four vaccinated monkeys were still resistant to the homologous SIV strain, and three of four monkeys were resistant to the heterologous SIVsm strain. This study demonstrates vaccine induced cross-protection between SIV strains.

Adjuvants, Immunologic↗

Recurrent otitis media with non-typable Haemophilus influenzae: the role of serum bactericidal antibody.

The effect of serum bactericidal antibody on colonization with non-typable Haemophilus influenzae (NTHI) was studied in 26 children. Serum bactericidal antibody did not prevent colonization with NTHI in the nasopharynx. Antibody was present in 53% before, 91% during and 100% after documented colonization of the nasopharynx with NTHI. In addition, 5 children with recurrent otitis media with effusion (OME) due to NTHI were observed for bactericidal serum antibody during a 4-year period. Bactericidal antibody against the causative NTHI strain was not detected in the acute sera of any patient during each episode, but was observed in the convalescent sera of all of the patients. The bactericidal antibody in the convalescent serum did not appear to be protective against colonization and recurrence of disease by a different heterologous strain of NTHI. However, bactericidal antibody was augmented in some cases by a heterologous infection with NTHI. We confirmed the emergence of new strains of NTHI with DNA fingerprinting and outer membrane protein (OMP) analysis. The data suggest that the immune response to NTHI in OME is usually strain-specific, and furthermore, the results demonstrate that strain-specific bactericidal antibody does not prevent colonization in the nasopharynx with the homologous or heterologous bacterial strains. In general, bactericidal antibody is not cross-protective against heterologous strains of NTHI causing a second or third episode of otitis media with NTHI.

Antibodies, Bacterial↗

Long-lived and transferable tumor immunity in mice after targeted interleukin-2 therapy.

A major goal of tumor immunotherapy is the induction of tumor-specific T cell responses that are effective in eradicating disseminated tumor, as well as mounting a persistent tumor-protective immunity. We demonstrate here that a genetically engineered fusion protein consisting of human/mouse chimeric anti-ganglioside GD2 antibody and human interleukin-2 is able to induce eradication of established B78-D14 melanoma metastases in immunocompetent syngeneic C57BL/6J mice. This therapeutic effect is mediated by host immune cells, particularly CD8+ T cells and is associated with the induction of a long-lived immunity preventing tumor growth in the majority of animals when challenged up to four months later with B78-D14 cells. This effect was tumor-specific, since no cross-protection against syngeneic, ganglioside GD2+ EL-4 thymoma cells was observed. Furthermore, this tumor-specific protection can be transmitted horizontally to naive, syngeneic SCID mice by passive transfer of CD8+ T lymphocytes derived from immune animals. These results suggest that antibody-targeted delivery of cytokines provides a means to elicit effective immune responses against established tumors in the immunotherapy of neoplastic disease.

Animals↗

Sustainable coccidiosis control in poultry production: the role of live vaccines.

The development of new methods of administering coccidiosis vaccines has facilitated their use in the hatchery and thereby improved prospects for the economic vaccination of broilers. The acquisition of protective immunity to Eimeria species is boosted by further exposure to infection after vaccination. Factors that affect the reproductive efficiency of non-attenuated and attenuated vaccines are considered and the key role that oocyst production plays in establishing and maintaining uniform immunity in a flock of chickens is discussed. In addition to immunisation, a possible advantage to the application of certain vaccines is that their use could repopulate poultry houses with drug-sensitive organisms. Theoretical rotation programmes in which the use of drugs is alternated with that of vaccines are described. Variability of the cross-protective immune response between strains of the same species should be considered during vaccine development and subsequent use. The significance of less common species of Eimeria, not included in all vaccines, also needs to be assessed. An important consideration is the occurrence of pathogens other than Eimeria (such as the bacterium Clostridium) in flocks given coccidiosis vaccines and the methods by which they might be controlled. More research is required into the relationship between bacterial and viral infections of poultry and coccidiosis vaccination. Vaccines need to be developed that are simple to apply and cost effective for use in areas of the world where small-scale poultry production is commonplace. In the near future it is likely that more live vaccines based upon oocysts derived from attenuated strains of Eimeria will be developed but in the longer term vaccines will be based on the selective presentation to the host of specific molecules that can induce protective immunity. This achievement will require significant investment from the private and public sectors, and, if successful, will facilitate the sustainable control of coccidiosis in poultry production.

Animals↗

Cache Valley and Potosi viruses (Bunyaviridae) in white-tailed deer (Odocoileus virginianus): experimental infections and antibody prevalence in natural populations.

Cache Valley virus (CVV) and Potosi virus (POTV) are two closely related mosquito-borne viruses (Bunyaviridae: Bunyamwera group) that appear to circulate in several regions of the United States, especially the Midwest. We determined the prevalence of specific neutralizing antibodies to both viruses in Indiana white-tailed deer and conducted infection experiments to assess whether deer could serve as an vertebrate-amplifying host. Cross-infection experiments also were carried out to investigate the level of antibody cross-reactivity and cross-protection between the two viruses. The seroprevalence rate was high for both CVV (> 66%) and POTV (> 43%) in adult deer statewide. Antibodies neutralizing CVV were more common among deer harvested in the northern part of Indiana whereas the prevalence of POTV antibodies suggested a more southern distribution for this virus. Experimental infections of captive deer showed that they may serve as amplifying hosts for either virus. Deer infected with CVV or POTV developed a 1-3-day viremia with 3.0 and 4.1 log10 plaque-forming units/ml mean peak titers, respectively. However, significant levels of antibody cross-reactivity between the two viruses were observed. Viremia was lower and shorter when animals immune to either CVV or POTV were cross-infected with the alternate virus and antibody responses following cross-infections resembled original antigenic sin with higher titers of antibodies against the primary agent.

Animals↗

Antigenic analysis of iron-regulated proteins in Pasteurella haemolytica A and T biotypes by immunoblotting reveals biotype-specific epitopes.

The antigenic relationships of the iron-regulated proteins (IRPs) in Pasteurella haemolytica A and T biotype strains were examined by SDS-PAGE and immunoblotting. P. haemolytica cells of the A biotype, grown under conditions of iron-limitation, expressed two IRPs, of 35 and 70 kDa. All T biotype strains expressed IRPs with slightly different molecular masses of 37 and 78 kDa. Immunoblotting of all 16 P. haemolytica serotypes was carried out using a panel of polyclonal and monoclonal antibodies raised against serotype A2 antigens. Polyclonal antibodies revealed inter-serotype cross-reactivity towards the 35 and 70 kDa IRPs within the A biotype but no cross-reactivity against a T biotype protein in the 78 kDa region. Monoclonal antibody against the 35 kDa antigen reacted only with the A biotype 35 kDa IRP. Identical profiles were obtained for 10 field isolates of serotype A2, further emphasizing the antigen conservation within the A biotype. These findings reinforce the view that the A and T biotypes of P. haemolytica should be considered as separate species and suggest that IRPs from single A and T biotype strains incorporated into a vaccine might provide cross-protection against all P. haemolytica serotypable strains. Similar studies on the IRPs of 10 untypable strains revealed some of these to have different antigenic reactivities from those observed within the A and T biotypes.

Antibodies, Bacterial↗

Epidemiologic aspects and diagnostic criteria for a protective efficacy field trial of a pertussis vaccine.

Pertussis was a major childhood disease in parts of West Germany in 1990. Before a prospective household contact trial into the efficacy of an acellular pertussis vaccine was undertaken, the epidemiology of the disease was studied in one area. This study showed that pertussis had an annual incidence of 4%-6% in the first 6 years of life. During the trial, a total of 1223 pertussis cases were diagnosed by laboratory methods. Isolation rates of Bordetella organisms varied by the pediatrician who did the nasopharyngeal swab and decreased with time required for swab transport. Analysis of the serologic results showed that if IgG and IgA anti-pertactin antibodies had been considered, overall sensitivity would have been only marginally increased. Several pertussis patients had antibodies to parapertussis antigens, indicating a lack of complete cross-protection. The serologic response in secondary household contacts differed by vaccination status. However, this difference was unlikely to have influenced the point estimate of efficacy of the acellular vaccine.

Antibodies, Bacterial↗

Cross-reaction between a strain of Vibrio mimicus and V. cholerae O139 Bengal.

Of 200 isolates of Vibrio mimicus screened, one from water (N-57) agglutinated with V. cholerae O139 polyclonal antiserum (absorbed with a rough strain of V. cholerae only) and not with O139 polyclonal diagnostic antiserum (absorbed with the rough strain and V. cholerae O22 and O155). The antigenic relationship between V. cholerae 0139 and N-57 is of a,b-a,c type, where a is the common antigenic epitope and b and c are unique epitopes. Strain N-57 was assigned to a new serogroup of V. cholerae O194. It gave negative results in a monoclonal antibody-based rapid test and a PCR test specific for V. cholerae O139. It did not possess the ctx gene or produce cholera toxin. Antiserum to strain N-57 cross-protected infant mice against cholera on challenge with V. cholerae O139. Structural studies of the surface polysaccharides and studies of the rfb genes will shed more light on the extent of relatedness between V. mimicus N-57 and V. cholerae O139.

Agglutination Tests↗