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Evaluation of a gel-immunization technique used with two different Immucox vaccine formulations in battery and floor-pen trials with broiler chickens.

The use of a gel-immunization technique with Immucox vaccination was compared and evaluated against other immunization methods in battery and floor-pen immunization trials. Gel immunization was found to be superior to immunization by gavage, by spray cabinet, or by the conventional delivery method of Immucox in a battery trial. Significantly enhanced protection as measured by weight gain, coupled with the establishment of a more uniform primary immunizing infection as evidenced by greater intestinal lesions and increased oocyst shedding, was seen in gel-immunized birds. In addition, cross-protective battery trials determined that the strain of Eimeria maxima found in the Immucox vaccine failed to elicit protection against a recent field isolate of E. maxima as measured by average weight gain and lesion scores. A reformulation of the Immucox vaccine that included the field isolate of E. maxima was required to elicit a protective immune response against challenge by the field strain. A floor-pen experiment demonstrated that gel immunization of 1-day-old roaster chickens resulted in performance parameters of average weight gain, average bird weight, and feed conversion that did not differ significantly from those recorded for medicated nonimmunized birds.

Animals↗

Construction and vaccine potential of acapsular mutants of Erysipelothrix rhusiopathiae: use of excision of Tn916 to inactivate a target gene.

We previously showed that acapsular transposon Tn916 mutants of Erysipelothrix rhusiopathiae are avirulent for mice. In this study, we constructed nonreverting acapsular mutants and examined the vaccine potential of the mutants in mice. A representative acapsular transposon mutant, 33H6, was plated on selective agar containing autoclaved chlortetracycline and quinaldic acid, and two tetracycline-sensitive mutants were obtained. Sequence analysis of chromosomal regions of the mutants in which Tn916 had flanked revealed that Tn916 had spontaneously excised from the region and that the six new nucleotides, which were presumably inserted with Tn916 into 33H6 chromosome, substituted for those present at the insertion site. The mutants were confirmed to be devoid of capsular antigen by Western immunoblotting and were nonvirulent for mice (subcutaneous 50% lethal dose [LD50], >10(9) CFU). The safety and efficacy of acapsular mutants for live vaccines was further studied by using one mutant strain, named YS-1. The YS-1 bacteria were cleared from the skin sites of inoculation, livers, and spleens of the inoculated mice by 7 days after subcutaneous (s.c.) inoculation. Mice immunized s.c. with doses ranging from 2 x 10(4) to 2 x 10(8) CFU of strain YS-1 were completely protected against challenge with 100 LD50 of the homologous, highly virulent strain Fujisawa-SmR 21 days postimmunization, and protective immunity conferred by immunization with 2 x 10(8) CFU of the strain lasted for as long as the 3 months of the observation period. In passive immunization experiments, sera collected from mice immunized with strain YS-1 at days 14 and 21 postimmunization provided protection against challenge with Fujisawa-SmR, whereas sera collected at days 4 and 7 did not. Furthermore, specific spleen cell responses to E. rhusiopathiae antigens were observed in mice immunized with strain YS-1, and cross-protection against the antigenically heterologous bacterium Listeria monocytogenes was observed at 7 days after immunization in the mice, suggesting that cell-mediated immunity had been induced. These results suggest that E. rhusiopathiae YS-1 may be a suitable choice for further studies of vaccine efficacy in swine.

Animals↗

Recent advances in vaccination against cysticercosis.

Progress in recent research towards vaccination against cysticercosis is reviewed briefly. An antigen of Taenia ovis has recently been cloned using recombinant DNA techniques and this single defined recombinant molecule has been shown to induce high-level protection against challenge infection in sheep. Prospects for the application of this discovery in T. ovis for development of effective vaccines against infection with the metacestodes of other taeniid parasites are discussed. The extent and level of cross protection between different taeniid species is reviewed. Recent research results defining stage-specific immune responses against T. taeniaeformis in mice following immunization with oncosphere and metacestode antigens is discussed in relation to the potential development of cocktail vaccines. Such vaccines may be capable of protecting against initial infection and the killing of those parasites which might evade the early-phase immune responses. Recent advances in the development of a practical vaccine against Taenia ovis infection in sheep raise the realistic prospect of the development of a similar vaccine against other taeniid parasites including T. solium. Advances in the understanding of vaccination - induced immune responses against T. taeniaeformis infection in mice also indicate that effective immunization may be capable of eliminating the establishment of any viable metacestodes.

Animals↗

Induction of cross-reactive serum neutralizing antibody to human rotavirus in calves after in utero administration of bovine rotavirus.

Sera from calves infected in utero or postnatally with bovine rotavirus NCDV or postnatally with human rotavirus D (serotype 1) were tested by plaque reduction neutralization assay for antibody to bovine rotavirus and to three serotypes of human rotavirus. Homologous antibody developed in all animals, but antibody to heterologous rotaviruses developed mainly in animals exposed in utero to bovine rotavirus. The development of heterologous antibody may explain the immunological implications for cross-protection, previously observed between bovine and human rotavirus in experimentally infected calves.

Animals↗

Identification of two cross-neutralizing linear epitopes within the L1 major capsid protein of human papillomaviruses.

The neutralizing activities of polyclonal antibodies and monoclonal antibodies (MAbs) obtained by immunization of mice with L1 virus-like particles (VLPs) were investigated by using pseudovirion infectivity assays for human papillomavirus type 16 (HPV-16), HPV-31, HPV-33, HPV-45, HPV-58, and HPV-59 to obtain a better definition of cross-neutralization between high-risk HPVs. In this study, we confirmed and extended previous studies indicating that most genital HPV genotypes represent separate serotypes, and the results suggest that the classification of serotypes is similar to that of genotypes. In addition, three cross-neutralizing MAbs were identified (HPV-16.J4, HPV-16.I23, and HPV-33.E12). MAb HPV-16.J4 recognized a conserved linear epitope located within the FG loop of the L1 protein, and HPV-16.I23 recognized another located within the DE loop. The results suggested that reactivity of MAb HPV-16.I23 to L1 protein is lost when leucine 152 of the HPV-16 L1 protein is replaced by phenylalanine. This confirmed the existence of linear epitopes within the L1 protein that induce neutralizing antibodies, and this is the first evidence that such linear epitopes induce cross-neutralization. However, the cross-neutralization induced by L1 VLPs represents less than 1% of the neutralizing activity induced by the dominant conformational epitopes, and it is questionable whether this is sufficient to offer cross-protection in vivo.

Amino Acid Sequence↗

Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model.

Mortality in colorectal cancer is associated with the development of liver metastases. Surgical removal of these tumors is the only hope for cure, but recurrence is common. During liver surgery, ischemia/reperfusion (I/R) often occurs as a result of hemorrhage or vascular clamping. Although the adverse effects of I/R on postoperative liver function are well documented, the influence of I/R on the outgrowth of residual micrometastases is unknown. We used a highly standardized mouse model of partial hepatic I/R to study the effects of I/R on the outgrowth of preestablished colorectal micrometastases. Five days following intrasplenic injection of C26 colon carcinoma cells, the vascular structures of the left lobe were clamped for 45 minutes under hemodynamically stable conditions. Tissue glutathione, plasma liver enzymes, hepatocellular necrosis, and tumor growth were assessed over time. I/R caused oxidative stress and early liver tissue damage. The outgrowth of micrometastases in occluded liver lobes was accelerated five- to sixfold compared with nonoccluded lobes and was associated with areas of necrotic liver tissue surrounded by inflammatory cells and apoptotic hepatocytes. Accelerated tumor growth and tissue necrosis were completely prevented by occluding blood flow intermittently. In contrast, ischemic preconditioning or treatment with the antioxidants alpha-tocopherol or ascorbic acid failed to protect against late tissue necrosis and tumor growth, although early hepatocellular damage was largely prevented by these methods. In conclusion, I/R is a strong stimulus of recurrent intrahepatic tumor growth. Measures to prevent I/R-induced late tissue necrosis cross-protect against this phenomenon.

Animals↗

Conflicting immune responses can prolong the length of infection in Plasmodium falciparum malaria.

We have recently proposed a new model for antigenic variation in Plasmodium falciparum that relies on a network of partially cross-protective immune responses to orchestrate this complex immune evasion process. In addition to exhibiting prolonged oscillations of single variants that resemble the sequential dominance of immunologically distinct antigenic types, the model implies that a higher efficacy of cross-reactive immunity actually increases the length of infection while reducing severity of disease. Here, we analyse the behaviour of a reduced system under conditions of perfect synchrony between variants to demonstrate that these features of this system can be attributed to the antagonism between cross-reactive and variant-specific responses.

Animals↗

Comparison of patterns of hybrid resistance to the BALB/c plasmacytomas LPC-1 and MPC-11.

Patterns of genetic control of hybrid resistance to the BALB/c plasmacytoma LPC-1 were studied for comparison with those to MPC-11, a plasmacytoma investigated previously. The overall patterns of hybrid resistance to the two tumors were similar, i.e., hybrids between BALB/c and BALB congenic resistant (CR) strains, A and A CR strains, SJL and DBA/2 were as susceptible to LPC-1 as BALB/c mice themselves, whereas hybrids between BALB/c and AKR, C57BL/Ks, DBA/1, C57BL/6 (B6), C57BL/10 (B10) and B10 CR strains were resistant to LPC-1 as previously shown with MPC-11. Heterozygosity within the H-2 complex alone was insufficient for resistance to either tumor. Among hybrids between BALB/c and the B10 CR strains, however, the presence of certain H-2 haplotypes influenced the degree of resistance seen and this H-2 effect was different for the two tumors. A sex effect on resistance to LPC-1, but not to MPC-11, was seen among F1 hybrids between BALB/c and DBA/1 although not in any other F1 hybrids. Among ((B10 X BALB/c)F1 X BALB/c) and (BALB/c X (B10 X BALB/c)F1) and ((BALB/c X B10)F1 X BALB/c) and ((BALB/c X B10)F1 X BALB/c) backcross mice, however, significantly more males than females were resistant to LPC-1 and the results of this study are compatible with the idea that in F1 hybrids between BALB/c and B10, resistance to LPC-1 is controlled by two dominant autosomal genes, one of which is sex-limited and neither of which is linked to H-2. In contrast, hybrid resistance to MPC-11 in this cross is controlled by a single gene. Cross-protection experiments indicated that the two tumors share at least one tumor-associated transplantation antigen.

Animals↗

Differentiation between two African arenaviruses (Lassa and Mozambique) by plaque assay.

The biological characteristics of Lassa and Mozambique viruses were compared by plaque assay. Both viruses produced plaques under the same conditions, however, Lassa virus plaques measured on average 2 mm in diameter being twice as large as the Mozambique virus plaques. By plaque reduction tests, cross protection was demonstrated between both viruses showing that Lassa and Mozambique viruses are distinct but related.

Animals↗

Epidemiology, subgroups and serotypes of rotavirus diarrhea in north Indian communities.

To know prevalence of rotavirus diarrhea subgroups and serotypes, a prospective study was conducted in rural, periurban and urban communities at Chandigarh. Weekly surveillance for diarrheal episodes was carried out in 110 families each from rural, periurban and urban localities constituting 584 children < 5 years of age from October, 1988 to February, 1991. Stool samples of 218 diarrheal episodes occurring in 115 children were subjected to rotavirus detection by ELISA. Rotavirus positive samples were further analyzed for subgroups and serotypes using specific monoclonal antibodies. Overall prevalence of rotavirus diarrhea was 4.3% (25/584). Rotavirus constituted 11.5% (25/218) of total diarrheal episodes and 22% (25/115) among the children affected with acute diarrhea. Among rural, periurban and urban communities, the overall prevalences of rotavirus diarrhea were 7.3%, 3.2% and 2.3% and episode related prevalences of 31.8%, 7.4% and 5%, respectively (chi 2 test for trend was highly significant from rural to periurban to urban localities). Forty per cent (10/25 of rotavirus positive samples were subgroup I and 60% (15/25) sub-group II. Of the 25 rotavirus strains, 40% (10) were serotype 2, 24% (n = 6) serotype 3 and 36% (n = 9) serotype 4. No definite temporal or seasonal pattern of rotavirus was observed; however, more of rotavirus diarrheal episodes (16%) occurred during winter season. Subgroups and serotypes were observed to cocirculate during the rotavirus episodes. Demonstration of serotypes in our field study imply that the vaccine to be used in our country must be cross protective to have an effective impact on rotavirus infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Molecular dynamics of the alpha-helical epitope of a novel synthetic lipopeptide foot-and-mouth disease virus vaccine.

A novel synthetic foot-and-mouth disease virus (FMDV) peptide vaccine consisting of a synthetic B-cell and macrophage activator covalently linked to an amphiphilic alpha-helical T-cell epitope was developed. The low molecular weight vaccine of 3400 daltons is composed of virus VP1 antigenic determinant and the immunologically active lipotripeptide tripalmitoyl-S-glyceryl-cysteinyl-seryl-serine (P3CSS) as built-in adjuvant. The vaccine, tripalmitoyl-S-glyceryl-cysteinyl-seryl-seryl-FMDV-VP1 (VP1 = serotype O1K 135-154) induces protection against homologous challenge and serotype-specific virus neutralizing antibodies in guinea pigs after single administration without further adjuvants or carriers. A P3CSS conjugate with the FMDV-VP1 segment 135-154 of strain O Wuppertal produced only poor cross-protection against challenge with O1K virus. The antigenic determinant VP1(135-154) is an amphiphilic alpha-helix, as shown by CD. Molecular dynamics simulations (MDS) carried out using the highly homologous alpha-helical alcohol dehydrogenase (ADH) segment H3 as starting conformation for VP1(138-149) suggest that the FMDV segment 138-149 may adopt alpha-helical conformation during binding to its T-cell receptor, and that the development of the system during MDS may be considered as the dissociation step of the complex.

Amino Acid Sequence↗

Endotoxin-neutralizing protein protects against endotoxin-induced endothelial barrier dysfunction.

Bacterial lipopolysaccharide induces tyrosine phosphorylation of paxillin, actin reorganization, and opening of the transendothelial paracellular pathway through which macromoles flux. In this study, lipid A was shown to be the bioactive portion of the lipopolysaccharide molecule responsible for changes in endothelial barrier function. We then studied whether endotoxin-neutralizing protein, a recombinant peptide that is derived from Limulus antilipopolysaccharide factor and targets lipid A, could block the effects of lipopolysaccharide on protein tyrosine phosphorylation, actin organization, and movement of 14C-bovine serum albumin across bovine pulmonary artery endothelial cell monolayers. In the presence of serum, a 6-h exposure to lipopolysaccharide (10 ng/ml) increased transendothelial 14C-albumin flux compared to the simultaneous media control. Coadministration of endotoxin-neutralizing protein (> or =10 ng/ml) with lipopolysaccharide (10 ng/ml) protected against lipopolysaccharide-induced barrier dysfunction. This protection was dose dependent, conferring total protection at endotoxin-neutralizing protein/lipopolysaccharide ratios of > or =10:1. Similarly, endotoxin-neutralizing protein was capable of blocking the lipopolysaccharide-induced endothelial cell responses that are prerequisite to barrier dysfunction, including tyrosine phosphorylation of paxillin and actin depolymerization. Finally, endotoxin-neutralizing protein cross-protected against lipopolysaccharide derived from diverse gram-negative bacteria. Thus, endotoxin-neutralizing protein offers a novel therapeutic intervention for the vascular endothelial dysfunction of gram-negative sepsis and its attendant endotoxemia.

Actins↗

Comparative study of rotavirus strains of bovine and rabbit origin.

Newborn calves were susceptible to infection with a rotavirus strain isolated from rabbits and, conversely, rabbits 4-5 weeks of age became ill and some died when inoculated with the rotavirus strain of bovine origin. However, the latter isolate appeared to be more virulent than the rabbit isolate in either calves or rabbits. Moreover, in reciprocal cross protection tests, carried out in calves and in rabbits, the rabbit rotavirus antiserum afforded only weak protection to challenge infection with either the homologous or the heterologous virus. By contrast, the protective level of the bovine rotavirus antiserum was relatively high.

Animals↗

Identification of immunodominant polypeptides common between Anaplasma centrale and Anaplasma marginale.

High titered antibody from rabbits immunized with Anaplasma centrale or from cattle recovered from A. centrale infection bound predominantly to several 33-36 kDa polypeptides present in both A. centrale and the Israel-NT isolate of Anaplasma marginale. High titered bovine antibody against the Israel-NT isolate of A. marginale also reacted predominantly with A. centrale polypeptides in this size range. The immunodominance of the 33-36 kDa polypeptides and their cross-reactivity indicate that these shared epitopes may be primarily responsible for the cross-protective immunity between A. centrale and A. marginale.

Anaplasma↗

HIV-2 antisera cross-neutralize HIV-1.

The neutralization properties of three independent HIV-2 isolates were examined in comparison with four diverse HIV-1 strains. Human sera containing antibodies specific to HIV-2 can cross-neutralize HIV-1. By contrast, HIV-1 sera are group-specific and have no neutralizing effect on HIV-2. Therefore, HIV-2 antigens may be important components for the development of broadly cross-protective AIDS vaccines.

Antibodies, Viral↗

Serotyping of avian infectious bronchitis viruses by the virus-neutralization test.

The antigenic relationships of 12 strains of infectious bronchitis virus (IBV) were evaluated by a virus-neutralization procedure similar to that used in typing human rhinoviruses. Such a procedure consists of reciprocal neutralization tests performed by reacting 32-320 EID50 or plaque-forming units of virus with 20 antibody units of antiserum. Eight serologic groups were identified by chicken embryo assay, and 4 by plaque-reduction (90%). In general, serologic groupings were not distinct but reflected numerous intergroup relationships. The contrasting results exhibited by indicator systems are viewed as differences in the accuracy of the methods employed. It is suggested that before an IBV classification scheme can be proposed, agreement must be reached on the most suitable indicator system, techniques must be standardized, and reference viruses and antisera distributed to several institutions for comparison testing. In addition, cross-protection studies are needed to determine the importance of IBV serotypes and/or variants on vaccine efficacy.

Animals↗

Assessment of the clinical and virological protection provided by a commercial inactivated bovine viral diarrhoea virus genotype 1 vaccine against a BVDV genotype 2 challenge.

A new genotype of bovine viral diarrhoea virus (BVDV), designated BVDV-2, has emerged in the last decade and in recent years the prevalence of BVDV-2 strains has increased. A vaccination-challenge study was carried out to determine the cross-protective efficacy of a commercial inactivated vaccine containing a BVDV-1 strain. A group of five BVDV-free calves was vaccinated twice and a second group of five calves served as negative controls. Two months after the first vaccination, all the calves were challenged intranasally with BVDV-2 strain BVD890. The clinical signs of disease, the changes in haematological variables and the level of viraemia were significantly less in the vaccinated group.

Animals↗

Data security and protection in cross-institutional electronic patient records.

This paper describes data protection and data security requirements of a cross-institutional electronic patient record, and presents possible solutions for meeting these requirements. A comprehensive analysis of literature and legal documents was performed. Beside the general requirements that the EPR of a single institution must meet, specific requirements exist for cross-institutional EPRs. In Germany, patient information may only be revealed to external physicians within so-called "treatment connections". A secure connection between the EPR-systems of two health institutions in Germany, which jointly treat tumor patients, was established using additional SecuRemote Software. The development and implementation of a cross-institutional EPR is a complicated process, mainly due to data security regulations. However, its introduction is thought to be valuable, since a cross-institutional EPR will improve communication within shared care processes, and, thus, improve the quality of patient care.

Computer Security↗