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PubMedDate not supplied

Chemical structure of and immune response to polysaccharides of Streptococcus pneumoniae.

By use of rabbit antisera, extensive cross-reactions were demonstrated among pneumococcal (Danish) types 6A and 6B, types 9N, 9A, 9L, and 9V, and types 19F and 19A. The structural similarity of the group 6 polysaccharides was associated with extensive immunogenicity in humans. In contrast, immunization of humans with type 19F or 19A may not induce sufficient cross-protection. The type 19F polysaccharide has the structure of a linear polymer of N-acetylmannosamine-glucose-rhamnose phosphate. Danish type 19A (type 57 in the United States system) polysaccharide contains this repeating unit and, in addition, has side chains of N-acetylglucosamine-galactose phosphate and fucose phosphate. Maternal immunization with type 19F or type 6A polysaccharide during pregnancy elicited high antibody formation in the offspring. Young mice, which received an additional dose of polysaccharide at two weeks of age, showed a higher antibody response than did those that did not receive polysaccharide. These studies reveal that the extensive cross-immunogenicity of pneumococcal group polysaccharides has a basis in chemical structure. Maternal immunization with pneumococcal polysaccharides may enhance the immune response of neonates.

Animals↗

PubMed2005

Surrogate tumor antigen vaccination induces tumor-specific immunity and the rejection of spontaneous metastases.

The nonimmunogenic 4T1 murine mammary carcinoma model and a model surrogate tumor antigen (sTA) were employed to explore the possibility of inducing tumor-specific immunity through active immunization in the absence of defined tumor-associated antigens. Immunization of naive mice with protein-based sTA resulted in protection from s.c. challenge, with 4T1 modified to express the sTA (4T1.sTA), or from a sTA-expressing unrelated tumor cell line (mKSA). Immunization had no effect on parental 4T1 tumor growth or the formation of parental 4T1 spontaneous lung metastases. Mice that were sTA immunized and successfully rejected 4T1.sTA challenge also rejected a subsequent challenge in the contralateral flank with parental 4T1 and strikingly prevented the formation of spontaneous parental 4T1 lung metastases. The rejection of parental 4T1 seemed to be specific for and associated with unknown 4T1 tumor-associated antigens, because rejection of mKSA did not induce cross-protection against a challenge with parental 4T1. To evaluate the effect of this vaccine approach on established disease, mice were simultaneously challenged on day 0 with 4T1.sTA and parental 4T1 in contralateral flanks and then immunized on days 3, 10, 17, and 24 with sTA protein. Tumor growth and metastasis were delayed in four of five animals, and 20% (2 of 5) of the animals were tumor free at the completion of the experiment. Together, these data suggest that prior vaccination with a sTA followed by inoculation with poorly immunogenic tumor cells modified to express the sTA activates determinant spreading and the induction of systemic tumor immunity resulting in indigenous tumor rejection.

Animals↗

PubMed1977

Immunization of chickens against adenovirus infection.

Chickens were vaccinated with monovalent and polyvalent adenovirus vaccines using three different serotypes, types 1, 2, and 3. No cross-protection was elicited by the heterologous serotypes but satisfactory protection from lesions and the shedding of challenge virus was induced by the homologous serotypes in the monovalent and polyvalent vaccines. The virus neutralizing (VN) titers were occasionally lower where the polyvalent vaccines were used when compared to those from chickens given the monovalent vaccines. This suggested possible interference though protection did exist against the appearance of lesions. Where chickens were vaccinated at an early age and in the presence of congenital homologous VN antibodies, protection against the effects of infection was satisfactory whereas the VN antibody titers were low or insignificant by the assay methods employed. The vaccine virus was not shed beyond 28 days after vaccination. No physical effects of vaccination were noted in any of the chickens during the post-vaccination period.

Adenoviridae Infections↗

PubMedDate not supplied

Pathogenicity of recent isolates of infectious bursal disease virus in specific-pathogen-free chickens: protection conferred by an intermediate vaccine strain.

The pathogenicity of recent isolates of infectious bursal disease virus and the protection conferred against them by a commercial vaccine strain of intermediate virulence were examined in specific-pathogen-free chickens. Based on clinical signs, mortality, and macroscopic lesions in susceptible chickens, the isolates designated as A-Delmarva and U-28 were distinct from a previously known serotype I virulent isolate (Edgar). Histopathological analysis of the bursa of Fabricius did not establish differences between the field isolates. Although the vaccine strain produced some degree of bursal damage in antibody-free chickens, it was significantly less severe than the damage caused by the field isolates. The active immune response induced by vaccination was cross-protective against the pathological effects produced by the different isolates used in this study.

Animals↗

PubMed1994

The detection of antibodies against peste des petits ruminants virus in cattle, sheep and goats and the possible implications to rinderpest control programmes.

Monoclonal antibody-based competitive ELISA (C-ELISA) have been used for the specific measurement of antibodies to both rinderpest and peste des petits ruminants (PPR) viruses in cattle, sheep and goats. Examination of serum samples from sheep and goats in Gambia, before and after vaccination with rinderpest vaccine, suggested that antibodies to PPR virus could prevent an immune response to the rinderpest vaccine. Cattle sera from Nigeria and Ghana showed a high prevalence of antibody against PPR virus which may explain the difficulty experienced in some countries in achieving high post-vaccination immunity levels against rinderpest. Because antibodies against PPR virus are both cross-neutralizing and cross-protective against rinderpest virus further vaccination in the presence of antibodies against PPR virus may be a waste of national resources. This paper presents serological evidence for the transmission of PPR virus from sheep and goats to cattle and highlights the need to include PPR serology in the sero-monitoring programme to give a better indication of national herd immunity.

Animals↗

PubMed2003

Evaluation of the protective efficacy of Vibrio cholerae ghost (VCG) candidate vaccines in rabbits.

An effective Vibrio cholerae vaccine is needed to reduce the morbidity and mortality caused by this pathogen. Despite the availability of current oral vaccines with measurable efficacy, there is need for more effective vaccines with broad-spectrum efficacy in target populations. Recent studies have shown that bacterial ghosts, produced by the expression of cloned lysis gene E, possess adjuvant properties and are immunogenic. In this study, ghosts were prepared from V. cholerae O1 or O139 and evaluated as vaccines in the reversible intestinal tie adult rabbit diarrhea (RITARD) model. Rabbits were orally immunized with different doses of V. cholerae ghost (VCG) formulations. The vaccine formulations elicited high levels of serum vibriocidal titers against indicator strains. The magnitude of the response was measured as the geometric mean titer (GMT) increase for all rabbits in relation to prevaccination titers. The induction of cross protection was evidenced by the ability of serum from VCG-immunized rabbits to mediate complement-dependent killing of both the homologous and the heterologous strains. Immunized rabbits were protected against intraduodenal challenge 30 days after primary immunization. Protective immunity against challenge appeared to be dose dependent and was associated with marked inhibition of colonization. These results indicate that VCGs represent a novel approach to cholera vaccine development and constitute an effective vaccine delivery vehicle.

Animals↗

PubMed1986

Tumor rejection antigens of chemically induced sarcomas of inbred mice.

Chemically induced sarcomas of inbred mice are immunogenic in syngeneic hosts, and preimmunization with tumor cells leads to resistance to subsequent tumor transplants. The tumor rejection antigens (TRAs) that mediate this reaction are highly specific for each tumor; cross-protection between different syngeneic sarcomas is rare. Isolated membrane and cytosol fractions from two antigenically distinct BALB/c sarcomas, Meth A and CMS5, have TRA activity, and biochemical characterization of the active components from the cytosol and plasma membranes of these two tumors identified a glycoprotein of Mr 96,000. Immunization with unfractionated Meth A cytosol frequently leads to tumor enhancement, but the tumor-enhancing activity (TEA) is lost on fractionation and TRA activity becomes demonstrable. As Meth A and CMS5 lack expression of murine leukemia virus (MuLV) antigens or transcripts, MuLV-related antigens cannot be involved in the TEA or TRA activities of these tumors. In contrast to the lack of cross-reactivity between Meth A and CMS5 TRAs in transplantation tests, rabbit antiserum prepared against the Meth A Mr 96,000 antigen reacted with the CMS5 Mr 96,000 antigen. In view of the biochemical and antigenic similarities of Meth A and CMS5 TRAs, we propose that structurally related but distinct Mr 96,000 glycoproteins are expressed in chemically induced sarcomas and that these molecules are responsible for the individually specific immunogenicity of these tumors.

Animals↗

PubMed1995

The stationary-phase sigma factor sigma S (RpoS) is required for a sustained acid tolerance response in virulent Salmonella typhimurium.

The acid tolerance response (ATR) of log-phase Salmonella typhimurium is induced by acid exposures below pH 4.5 and will protect cells against more extreme acid. Two systems are evident: a transiently induced system dependent on the iron regulator Fur that provides a moderate degree of acid tolerance and a more effective sustained ATR that requires the alternate sigma factor sigma S encoded by rpoS. Differences between the acid responses of virulent S. typhimurium and the attenuated laboratory strain LT2 were attributed to disparate levels of RpoS caused by different translational starts. The sustained ATR includes seven newly identified acid shock proteins (ASPs) that are dependent upon sigma S for their synthesis. It is predicted that one or more of these ASPs is essential for the sustained system. The sustained ATR also provided cross-protection to a variety of other environmental stresses (heat, H2O2 and osmolarity); however, adaptation to the other stresses did not provide significant acid tolerance. Therefore, in addition to starvation, acid shock serves as an important signal for inducing general stress resistance. Consistent with this model, sigma S proved to be induced by acid shock. Our results also revealed a connection between the transient and sustained ATR systems. Mutations in the regulator atbR are known to cause the overproduction of ten proteins, of which one or more can suppress the acid tolerance defect of an rpoS mutant. One member of the AtbR regulon, designated atrB, was found to be co-regulated by sigma S and AtbR. Both regulators had a negative effect on atrB expression. The results suggest AtrB serves as a link between the sustained and transient ATR systems. When sigma S concentrations are low, a compensatory increase in AtrB is required to engage the transiently induced, RpoS-independent system of acid tolerance. Results also suggest different acid-sensitive targets occur in log-phase versus stationary-phase cells.

Acids↗

PubMed2004

Tick-borne encephalitis and the impact of vaccination.

TBE virus is endemic in many parts of Europe and Northern Asia, and in these regions it causes more than 10,000 severe cases of central nervous system disease in humans each year. The virus is primarily transmitted to humans when infected ticks take a blood meal, but infections due to the consumption of unpasteurized milk, primarily from goats, occur in certain regions. Based on genetic analyses, three closely related subtypes can be distinguished and are designated European, Siberian, and Far Eastern subtype according to their primary geographic distribution. Consistent with their close antigenic relationships, immunization studies in animals have revealed a high degree of cross-protection between virus strains belonging to different subtypes. The commercially available vaccines in Europe consist of highly purified inactivated whole TBE virus. Austria is the country with the highest coverage of TBE vaccination (86% of the total population) and this has led to a dramatic reduction in the annual number of clinical cases and proves under field conditions that vaccination is an effective means for the prophylaxis of TBE.

Animals↗

PubMed1999

Cross-reactivity between six Enterobacteriaceae complete lipopolysaccharide core chemotypes.

To gain insight into the value of lipopolysaccharide (LPS) core determinants for cross-protective immunisation the serological relationships between six complete (LPS) core types from Enterobacteriaceae were investigated. Hyperimmune sera were raised in mice by repeated immunisation with heat-killed strains of Salmonella choleraesuis (Ra core type) or Escherichia coli (core types R1, R2, R3, R4 and K12) and characterised for reactivity with complete and incomplete core chemotypes by ELISA and immunoblotting. Three sera (anti-Ra, anti-R2 and anti-R3) reacted strongly with 3-5 different complete core types whereas the other three (anti-R1, anti-R4 and anti-K12) reacted strongly only with their homologous core types in these assays. Two approaches were used to examine further the structural bases for cross-reactivity between these cores. By the first approach the anti-complete-core sera were tested for cross-reactivity with truncated forms of the Salmonella species core (incomplete cores) derived from core-defective mutants. By the second approach, antisera raised against some core-defective mutants were tested for cross-reactivity with complete cores. The results of these investigations revealed that several pair-wise combinations of core types can be used as immunogens to elicit immune responses that recognise all six core types and that the major determinants which mediate cross-reactivity between complete cores are localised in the outer core region.

Animals↗

PubMed1978

The serological and immunological relationship of type strains A and D of Pasteurella multocida to field isolates from sheep.

Investigations with antisera prepared in rabbits and sheep and active immunity experiments in mice showed that strains of Pasteurella multocida which, according to the haemagglutination test, are serologically related, do not necessarily give rise to cross immunity. Conversely, it was found that serologically unrelated strains may exhibit an appreciable degree of cross protection. The unreliability of the haemagglutination test as an indicator of immunological identity of strains was further confirmed in that peritoneal fluid from immunized mice showed passive protection properties despite the absence of haemagglutinating antibodies. There was no consistent agreement between the results obtained with antisera prepared in different species and active immunity experiments in mice, and this leads to the conclusion that different species probably vary quantitatively and qualitatively in their immune response to immunization with P. multocida. Attempts to determine whether combined bacterins afforded a better immunity than monovalent bacterins were inconclusive.

Animals↗

PubMed2005

Vaccine potential of recombinant Ornithobacterium rhinotracheale antigens.

Ornithobacterium rhinotracheale is a pathogen involved in respiratory infection and systemic disease in poultry. Previously, eight potential vaccine candidates were identified that induced cross-protective immunity when administered to chickens as a multi-component vaccine. In this study, we analyzed the immunogenicity of these eight recombinant proteins by subunit vaccination, and characterized the different proteins and corresponding genes more thoroughly by sequencing, in vitro expression analysis, and cellular localization experiments. We found, that all genes encoding the eight antigens were highly conserved among different O. rhinotracheale serotypes, but the different antigens were not expressed by all serotypes. Cellular fractionation experiments indicated that the majority of the antigens are predominantly located in the outer membrane fraction. Vaccination of chickens with single-antigen vaccines demonstrated that the Or77 antigen was protective against serotypes that expressed Or77 in vitro, suggesting that the protein has strong potential as a vaccine antigen. Furthermore, immunization with four-component subunit vaccines indicated the existence of immunogenic synergism between the candidate vaccine antigens.

Air Sacs↗

PubMed2006

A fused gene of nucleoprotein (NP) and herpes simplex virus genes (VP22) induces highly protective immunity against different subtypes of influenza virus.

We evaluated the immunogenicity and protective activity of plasmid DNA vaccines encoding the influenza virus NP gene (pNP) alone or in combination with the herpes simplex virus type 1 protein 22 gene (pVP22). Optimal immune responses were observed in BALB/c mice immunized with the combination of pVP22 plus pNP, as assessed by enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICCS). These mice also showed maximal resistance following challenge with the A/PR/8/34 (H1N1) and A/Udron/72 (H3N2) strains of influenza virus. The susceptibility of immunized mice to virus infection was significantly increased following depletion of either CD4+ or CD8+ T cells. These results indicate that a plasmid DNA vaccine encoding pVP22 plus NP induces a high level of cross-protective immunity against influenza virus subtypes.

Animals↗

PubMed2001

An inactivated bovine virus diarrhoea virus (BVDV) type 1 vaccine affords clinical protection against BVDV type 2.

This study was designed to answer to two distinct questions. Firstly, is it possible to reproduce clinical signs of acute bovine virus diarrhoea virus (BVDV) type 2 infection including signs of haemorrhagic disease under experimental conditions in cattle at 20 weeks of age? Secondly, what is the extent of the protection afforded by vaccination with an inactivated BVDV type 1 vaccine against BVDV type 2 infection? Calves were vaccinated at 12 and 16 weeks of age with a commercially available inactivated BVDV type 1 vaccine (Bovilis BVD). At 20 weeks they were challenge infected with BVDV type 2 virus together with unvaccinated control calves. The unvaccinated animals developed typical signs of respiratory disease, diarrhoea with erosions and haemorrhages along the whole length gastro-intestinal tract, and depletion of lymphocytes in lymphatic organs. These signs were either absent or markedly less severe in the vaccinated animals. The beneficial effects of vaccination were most striking in the haematological parameters thrombocytopenia and leukopenia. It can be concluded that vaccination with Bovilis BVD affords cross-protection against clinical effects of a challenge-infection with heterologous type 2 BVDV.

Animals↗

PubMed1988

Immunization of cattle with a 36-kilodalton surface protein induces protection against homologous and heterologous Anaplasma marginale challenge.

Immunization of cattle with a purified Anaplasma marginale major surface protein, AmF36, induced protection against homologous challenge with the Florida isolate. Similarly, immunized cattle were protected from challenge with the antigenically and structurally distinct Washington-O isolate of A. marginale. The degree of protection in AmF36-immunized cattle varied from complete prevention of rickettsemia to significant delay in the onset of rickettsemia compared with control immunized cattle. A single AmF36 vaccinate was not protected against homologous challenge despite development of a strong antibody response. Immunoprecipitation of A. marginale proteins with a monoclonal antibody to AmF36 identified minor molecular size heterogeneity in this protein from different isolates, including the Florida and Washington-O isolates. The apparent molecular size of this surface protein in the Florida isolate was 36 kilodaltons, whereas the analogous proteins in Washington-O and four other isolates of A. marginale from the United States had molecular masses of 33 to 34 kilodaltons. Significantly, the surface-exposed peptides of these proteins appear to be conserved among the different isolates. These results demonstrate the potential of AmF36 as a subunit immunogen for bovine anaplasmosis and indicate a structural basis for its cross-protective ability.

Anaplasma↗

PubMedDate not supplied

Induction of protective antitumor immune response against a murine plasmacytoma not curable by alkylating-drug treatment.

Immunization with viable tumor cells followed by subsequent administration of glutaraldehyde-treated tumor cells induced a protective antitumor immune response in the host toward the alkylating-drug resistant RPC-5 plasmacytoma. This was proven by resistance to challenge with RPC-5 tumor cells, neutralization in Winn tests, by effectiveness of combined chemotherapy with melphalan plus immunotherapy with spleen cells from RPC-5 immunized mice and in vitro by cytotoxicity tests. The specificity of the immune response was ascertained in vivo by comparison with the response toward MOPC-315 plasmacytoma. However, in vitro cytotoxicity tests revealed the occurrence of shared antigens between the RPC-5 and MOPC-315 tumor cells. It is concluded that the ineffectiveness of alkylating-drug treatment toward the RPC-5 tumor is not due to the inability of this tumor to induce a specific antitumor immune response, and that cross-antigenic relationship as revealed by in vitro cytotoxicity tests does not necessarily reflect cross-protection between various plasmacytomas.

Animals↗

PubMed1953

Problems of antivenene standardization revealed by the flocculation reaction.

Mixed with either of the specific venoms, refined antivenene (anti-Bitis arietans-Naja flava) will show optimal flocculation at a number of different venom: serum ratios. This is the natural consequence of individual antigen-antibody reactions in a heterogeneous system.Toxin may be recovered from floccules formed at three optimal N. flava venom: serum ratios by heating the floccules at 70 degrees C for ten minutes at pH 2. These three immunologically distinct heat-stable toxins have been called the alpha, beta, and gamma toxins of N. flava venom.The flocculation reaction obtained with the viperine venom cannot be interpreted in terms of protective potency.Most venom-antivenene systems fail to conform with the "law of combination in multiple proportions", i.e., they give non-linear titration curves. The shape of such curves, convex towards the dose axis, is readily explained by the simultaneous titration of multiple toxin-antitoxin systems.In the particular case of N. flava venom-antivenene, the titration curve obtained with whole venom is determined by the relative anti-alpha, anti-beta, and anti-gamma contents of the serum. Further study may pave the way to the standardization of the anti-alpha, anti-beta, and anti-gamma potencies of sera, but attempts at standardizing antivenene potency against any venom are futile unless the toxic "make-up" of the venom is understood.The cross-protection afforded by sera produced against either N. flava venom, or the venom of Sepedon haemachates is limited but indicates an antigenic similarity which may be clarified by work in progress.

Flocculation↗

PubMed1997

Pilin-based anti-Pseudomonas vaccines: latest developments and perspectives.

Among the several adhesins produced by Pseudomonas aeruginosa (Pa), the type-4 pilus promotes the majority of the adherence capability of the bacterium to epithelial cells and it is a major virulence factor in an AB.Y/SnJ mouse infection model. Vaccines targeting the disulfide loop (DSL) adherence binding domain of the pilin protein should therefore provide an effective protection against initial colonization and infection with Pa. To selectively elicit adherence blocking antibodies, the pilin DSL domain was chosen as peptide antigen for the construction of recombinant protein and live vaccines. While synthetic peptide-carrier protein conjugates provided some strain-specific protection, chimeric proteins with N- or C-terminally fused pilin DSL peptides did not engender protective IgG titers mice. Integral fusions of the pilin DSL peptide with the minor coat protein of filamentous phage or surface exposed regions of an outer membrane protein resulted in a display of the peptide on the surface of the phage particles and bacterial cells respectively. However, in immunization studies neither of these live vaccines were effective immunogens. The paracrystalline S-layer of Caulobacter crescentus combines several advantages of an effective antigen surface display system. Recombinant S-layer proteins with singlecopy insertions of a pilin peptide did not engender significant IgG titers, whereas multiple tandem insertions of the same peptide increased the serum IgG response in mice a thousand times. Multiple insertions of DSL peptides from different frequent pilin prototypes may be an interesting alternative for a recombinant cross-protective anti-Pseudomonas vaccine.

Amino Acid Sequence↗