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PubMed2003

Evaluation of a modified live virus type-1a bovine viral diarrhea virus vaccine (Singer strain) against a type-2 (strain 890) challenge.

Both type-1 and type-2 bovine viral diarrhea virus (BVDV) infections are responsible for major losses in the cattle industry. However, several commercial BVDV vaccines contain only a type-1 strain. A vaccine trial was conducted to evaluate the efficacy of BVDV type-1 (Singer strain; BVDV-1) vaccine for protecting calves challenged with virulent BVDV type-2 (890 strain; BVDV-2). Thirty-eight BVDV-negative calves were randomly allocated to four groups. One group was treated with a modified live virus (MLV) BVDV-1 vaccine by i.m. injection and another group was treated with the same vaccine by s.c. injection. Two groups served as nonvaccinated controls (one i.m. and one s.c.). Twenty-eight days following vaccination, the calves were challenged with BVDV-2 and monitored for 21 days. Clinical scores and body temperatures of vaccinated calves were significantly (P<.05) lower than for controls on several days, and peak differences occurred 8 days after challenge. The control calves had significantly (P<.05) lower leukocyte counts 3 through 8 days after challenge; leukocyte counts for vaccinated animals did not decline significantly from prechallenge levels. There were no differences in protection between the i.m. and s.c. routes of vaccination. The study demonstrated satisfactory cross protection of the BVDV-1 vaccine against BVDV-2 challenge.

Animals↗

PubMed1983

The determination of dissociation constants for substance P and substance P analogues in the guinea pig ileum by pharmacological procedures.

The dissociation constants (Kd values) of substance P (SP), physalaemin, kassinin, and SP analogues acting on SP receptors in guinea pig ileal longitudinal muscle strips were determined by the pharmacological procedures of Furchgott [Adv. Drug Res. 3:21-55 (1966)]. This method involves analysis of the concentration-response data before and after fractional inactivation of receptors with phenoxybenzamine (2 X 10(-5) M). Estimations of the Kd values for SP were similar when phenoxybenzamine was incubated for 10, 13, or 15 min. Coincubation with high concentrations of SP protected against receptor inactivation with phenoxybenzamine, but bradykinin and serotonin did not cross-protect SP receptors. Kd values for SP were similar when trypsin was substituted for phenoxybenzamine [Kd = 8.1 +/- 4 nM (n = 9) versus 10 +/- 6 nM (n = 5)]. In atropinized preparations the Kd values obtained for physalaemin were similar to those obtained for untreated preparations [Kd = 8.0 +/- 3.6 nM (n = 5) and 12.6 +/- 3 nM (n = 4), respectively]. The effects of phenoxybenzamine on concentration-response curves for kassinin showed greater shifts to the right with phenoxybenzamine. This indicated that kassinin may interact with another population of receptors, in addition to the sites that SP and other analogues bind. A direct correlation was found between EC50 values and Kd values and Kd values for SP and SP analogues. It was estimated that, for SP, a 20% receptor occupancy is required to elicit a 50% response.

Animals↗

PubMed2004

The auxotrophic aroA mutant of Aeromonas hydrophila as a live attenuated vaccine against A. salmonicida infections in rainbow trout (Oncorhynchus mykiss).

An auxotrophic aroA mutant of the Aeromonas hydrophila AG2 strain is a live attenuated vaccine against A. hydrophila infection in rainbow trout (Oncorhynchus mykiss). The protection conferred by the live attenuated vaccine against A. salmonicida strains is reported here, and several parameters of the specific and non-specific immune response in vaccinated trout were characterised. Vaccination with a dose of 10(7)cells/fish of the aroA mutant elicited significant protection against the Hooke and DK30 strains of A. salmonicida (relative percent survival RPS >60%). This cross-protection correlated moderately with the activation of the humoral and cellular specific immune responses, which show cross-reactivity against antigens shared by the two bacterial species, and a moderate increase in the lysozyme and antiprotease activities in the serum of vaccinated trout.

Aeromonas↗

PubMedDate not supplied

Immunity induced by live attenuated Salmonella vaccines.

Studies on the degree and specificity of protection conferred by immunization with aroA salmonella live vaccines in BALB/c mice are described. Animals were immunized i.v. and challenged orally 3 months later to ensure that the vaccine had been cleared from the tissues. Vaccination with Salmonella typhimurium aroA SL3261 conferred very good protection against virulent S. typhimurium C5 (over 10,000 x LD50). The specificity of cross protection was studied using S. typhimurium, Salmonella enteritidis and Salmonella dublin for vaccination and challenge, including challenge with variants of S. typhimurium and S. enteritidis of similar virulence which differed in the main LPS (lipopolysaccharide) antigen (0-4 or 0-9). S. typhimurium SL3261 gave very good protection against S. typhimurium C5 (0-4), but no protection against S. enteritidis Se795 (0-9). However, challenge with strains differing in the main 0 antigens showed that, although protection was generally better to strains expressing the same LPS type as the vaccine, specificity of protection was determined more by the background (S. typhimurium or S. enteritidis) of the parent strain used for the challenge than by 0 factors 4 or 9, suggesting that other factors could be involved. The nature of the antigen(s) responsible for protection in this model is unclear, but it would not appear to be the main 0-specific antigen. An S. enteritidis Se795 aroA vaccine was far less effective than S. typhimurium SL3261; it conferred good protection against the homologous wild type at 2 weeks post-vaccination, but far less at three months (approx 10-200 x LD50). This was unexpected, as the persistence of the S. enteritidis vaccine in the liver and spleen was similar to that of S. typhimurium SL3261, and the S. enteritidis and S. typhimurium challenge strains were of similar virulence. An S. dublin aroA vaccine conferred similar protection against wild type S. dublin (approx 300 x LD50).

Animals↗

PubMed2002

Newcastle disease virus (NDV) marker vaccine: an immunodominant epitope on the nucleoprotein gene of NDV can be deleted or replaced by a foreign epitope.

The nucleoprotein (NP) of Newcastle disease virus (NDV) functions primarily to encapsidate the virus genome for the purpose of RNA transcription, replication, and packaging. This conserved multifunctional protein is also efficient in inducing NDV-specific antibody in chickens. Here, we localized a conserved B-cell immunodominant epitope (IDE) spanning residues 447 to 455 and successfully generated a recombinant NDV lacking the IDE by reverse genetics. Despite deletion of NP residues 443 to 460 encompassing the NP-IDE, the mutant NDV propagated in embryonated specific-pathogen-free chicken eggs to a level comparable to that of the parent virus. In addition, a B-cell epitope of the S2 glycoprotein of murine hepatitis virus (MHV) was inserted in-frame to replace the NP-IDE. Recombinant viruses properly expressing the introduced MHV epitope were successfully generated, demonstrating that the NP-IDE not only is dispensable for virus replication but also can be replaced by foreign sequences. Chickens immunized with the hybrid recombinants produced specific antibodies against the S2 glycoprotein of MHV and completely lacked antibodies directed against the NP-IDE. These marked-NDV recombinants, in conjunction with a diagnostic test, enable serological differentiation of vaccinated animals from infected animals and may be useful tools in ND eradication programs. The identification of a mutation-permissive region on the NP gene allows a rational approach to the insertion of protective epitopes and may be relevant for the design of NDV-based cross-protective marker vaccines.

Amino Acid Sequence↗

PubMed1986

Opioid analgesia in the mouse: evidence for multiple receptors using beta-FNA.

The icv injection of morphine or DADLE ED50 a few min before the alkylating agent beta-FNA resulted in complete protection of their respective analgesic effects when evaluated 24h later, although a little cross-protection could be observed. The analgesia evoked by DADLE was partially protected using higher doses of morphine before beta-FNA. However, higher doses of DADLE did not protect the analgesia induced by morphine. On the other hand, the antagonistic action of KCl on opioid analgesia was found to be dependent on the opioid utilized to protect the opioid receptor against the effect of beta-FNA. These results are discussed in terms of multiple receptors mediating opioid analgesia at supraspinal level in the mouse.

Analgesia↗

PubMed1983

Immunity to pasteurellosis in compromised rabbits.

Pasteurellosis in the rabbit inoculated with a malignant variant of Shope fibroma virus (SFV-MV) is presented as a model for the study of immunosuppression and immunoprophylaxis in pasteurellosis. The rabbits, before the inoculation, were healthy carriers of Pasteurella multocida. They were intradermally inoculated with SFV-MV, and 3 to 6 days later, a primary tumor appeared at the site of inoculation. By postinoculation day (PID) 7 or 8, the rabbits had snuffles, conjunctivitis, and tumor metastases; death occurred on PID 10 to 14. Rabbits given the nonmalignant Patuxent strain of SFV developed local primary tumors, but not pasteurellosis nor metastases. In SFV-MV-inoculated rabbits, there was decreased responsiveness of spleen lymphocytes to B and T cell mitogens by day 6, and of spleen and peripheral blood lymphocytes by day 10. In addition, SFV-MV antigen was detected (by immunofluorescence) in mononuclear phagocytes in all major organs and in epithelial cells of the conjunctiva and nasal mucosa. Both nasal and conjunctival epithelia showed squamous metaplasia as well. These changes did not appear in SFV-infected rabbits. With SFV-MV-inoculated rabbits, we obtained partial protection against pasteurellosis by immunization with heat-killed P multocida or a cross-protective core lipopolysaccharide mutant of Escherichia coli (J5). Rabbits were immunized before the inoculation with SFV-MV which precipitated "spontaneous" pasteurellosis due to impaired defenses. Rabbits immunized with J5 or P multocida had less severe conjunctivitis and snuffles than nonimmunized controls, indicating that immunization with the J5 mutant may be useful as prophylaxis against pasteurellosis in compromised hosts.

Animals↗

PubMed1994

Comparison of serum responses in swine after vaccination and challenge exposure with Actinobacillus pleuropneumoniae serotype 1.

Clinical trials have shown that currently available commercial vaccines against porcine pleuropneumonia provide inconsistent, serotype-specific protection from the disease. Recovery from naturally acquired infection, however, provides solid, serotype cross-protective immunity. We examined various serum responses of pigs receiving 1 of 4 commercial vaccines or a cell extract, and compared the serologic responses of these pigs after challenge exposure with virulent Actinobacillus pleuropneumoniae serotype 1. Evaluation of serum included complement-mediated killing, opsonizing capacity, IgG titers to whole organisms, and cytotoxin neutralization titers. Pigs that received the cell extract had fewer clinical signs of pleuropneumonia than pigs in other vaccinated groups, and also were significantly (P < 0.05) better protected from development of lung lesions and death. Such vaccinates were the only pigs that developed significant (P < 0.05) serum antibody titers (ie, protective immune response) to whole-cell antigens and to cytotoxin.

Actinobacillus Infections↗

PubMed1985

Immunological study of Pseudomonas aeruginosa extracellular slime.

Crude extracellular slime (C-ES) was isolated from 15 laboratory strains of Pseudomonas aeruginosa. Glycolypoprotein (GLP) was prepared from partially purified C-ES by the phenol treatment method. Lipopolysaccharides (LPS) were isolated from P. aeruginosa and Salmonella typhi-murium. Some correlation has been found between the quantity of the produced C-ES and virulence of P. aeruginosa for mice. Toxicity (LD50 value) and the yield of GLP did not correlate with the strain virulence. C-ES and GLP contained hexose, protein and hexosamine. Heptoses (characteristic LPS components) were present in C-ES and practically absent from GLP. Paper chromatographic analysis of GLP showed the presence of uronic acids, galactose, glucose and ribose in all strains; GLP of most strains contained rhamnose and a low amount of mannose and several strains xylose. Uronic acids, galactose and, probably, ribose and mannose were characteristic ES components. C-ES and GLP were studied in active and passive mouse protection. ES isolated from P. aeruginosa strains of different O serogroups or immunotypes induced a marked cross protective response.

Antigens, Bacterial↗

PubMed1999

Enhanced protection against a lethal influenza virus challenge by immunization with both hemagglutinin- and neuraminidase-expressing DNAs.

The ability of plasmid DNA encoding hemagglutinin (HA), neuraminidase (NA) or matrix protein (M1) from influenza virus A/PR/8/34 (PR8) (H1N1), and mixtures of these plasmid DNAs (HA + NA and HA + NA + M1) to protect against homologous or heterologous virus infection was examined in BALB/c mice. Each DNA was inoculated twice, 3 weeks apart, or four times, 2 weeks apart, at a dose of 1 microg of each component per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after the last immunization, mice were challenged with a lethal homologous or heterologous virus and the ability of each DNA to protect the mice from influenza was evaluated by observing lung virus titers and survival rates. The administration of a plasmid DNA mixture of either (HA + NA) or (HA + NA + M1) provided almost complete protection against the PR8 virus challenge, and this protection was accompanied by high levels of specific antibody responses to the respective components. The degree of protection afforded in these groups is significantly higher than that in mice given either HA- or NA-expressing DNA alone, which provided only a partial protection against PR8 challenge or that in mice given M1-expressing DNA, which failed to provide any protection. In addition, both of the plasmid DNA mixtures (HA + NA) and (HA + NA + M1) showed a slight tendency to provide cross-protection against an A/Yamagata/120/86 (H1N1) virus challenge, and this was accompanied by a relatively high level of cross-reacting antibodies. Thus, there was no clear difference between the ability of the HA + NA and HA + NA + M1 plasmid DNA mixtures in providing protection against either a PR8 or heterologous virus challenge. These results suggest that in mice immunized by gene gun, a mixture of plasmid DNAs encoding HA and NA can provide the most effective protection against the virus challenge. The addition of the M -expressing plasmid DNA to this mixture does not enhance the degree of protection afforded.

Animals↗

PubMed1986

Immunogenicity of potassium thiocyanate extract of type A Pasteurella multocida.

The immunogenicity and cross-protectivity of potassium thiocyanate (KSCN) extracts from Type A Pasteurella multocida strains were evaluated in mice. Mice administered KSCN extracts showed signs of depression for several hours following immunization. These extracts induced protection against challenge with the virulent homologous bacterium although many of the surviving mice were clinically ill up to 72 h after challenge exposure. There was no consistent reciprocal protection between different strains of the serotype indicating lack of correlation between serotype and cross-immunogenicity. Antigenic analysis of KSCN extracts by crossed immunoelectrophoresis techniques revealed greater than or equal to 25 different antigenic components. When the antigenic content of P-2383 and P-1062 KSCN extracts were compared, most antigenic components were common to both; however, two strain-specific and antigenic components were identified with homologous and heterologous antisera. One component present in each of the extracts gave a precipitation line similar to that produced by a crude lipopolysaccharide extracted from the organism. This component was isolated by sucrose density gradient centrifugation. The component isolated from P-2383 KSCN extract sedimented rapidly, indicating a high molecular weight material, and contained 12% carbohydrate and 27% protein. Immunization of mice with this component induced resistance to challenge with the homologous strain and some degree of protection against certain heterologous strains.

Animals↗

PubMed1990

Heterotypic protection induced by synthetic peptides corresponding to three serotypes of foot-and-mouth disease virus.

Synthetic peptide vaccines of the general sequence Cys-Cys(200-213)-Pro-Pro-Ser-(141-158)-Pro-Cys-Gly, where the numbered residues refer to VP1 sequences of three different strains of foot-and-mouth disease virus, have been evaluated in cattle and guinea pigs. High levels of serotype-specific (homotypic) antiviral and antipeptide antibody were produced with each peptide. The A- and O-serotype peptides provided complete protection of guinea pigs against their respective virus challenges. The C-serotype peptide appeared to be less effective than the other peptides. In cross-protection studies (heterotypic) in guinea pigs, it was possible to protect A-serotype peptide-vaccinated animals against O-virus challenge and vice versa. Some heterotypic protection was also achieved with the C-serotype peptide. The heterotypic protection observed related more to the presence of cross-reactive antipeptide antibody than to neutralizing antibody.

Amino Acid Sequence↗

PubMed1991

Efficacy of nucleoprotein and haemagglutinin antigens expressed in fowlpox virus as vaccine for influenza in chickens.

Fowlpox virus (FPV) recombinants expressing influenza virus H5 haemagglutinin (HA), nucleoprotein (NP) or co-expressing both of these antigens were tested for vaccine efficacy in chickens. Immunization with the recombinant FPV-HA was highly efficacious but provided no cross protection between subtypes. Bursectomy established that immunity against the H5 subtype was antibody-mediated despite the presence of very low levels of antibody in the vaccinated birds. Immunization with the recombinant FPV expressing the cross-reactive NP antigen did not provide protective immunity despite hyperimmunization and provided no benefit above HA expressed alone. The results suggest that the kinetics of viral replication outpaces immunity induced by NP.

Animals↗

PubMed2004

Broad spectrum resistance to ssDNA viruses associated with transgene-induced gene silencing in cassava.

Geminiviruses are ssDNA viruses that infect a range of economically important crop species. We have developed a pathogen-derived transgenic approach to generate high levels of resistance against these pathogens in a susceptible cultivar of cassava (Manihot esculenta). Integration of the AC1 gene (which encodes the replication-associated protein) from African cassava mosaic virus imparted resistance against the homologous virus and provided strong cross-protection against two heterologous species of cassava-infecting geminiviruses. Short-interfering RNAs specific to the AC1 transgene were identified in the two most resistant transgenic plant lines prior to virus challenge. Levels of AC1 mRNA were suppressed in these plants. When challenged with geminiviruses, accumulation of viral DNA was reduced by up to 98% compared to controls, providing evidence that integration of AC1 initiates protection against viral infection via a post-transcriptional gene silencing mechanism. The robust cross-resistance reported has important implications for field deployment of transgenic strategies to control geminiviruses.

Blotting, Northern↗

PubMed2006

Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial.

BACKGROUND: Effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions. Our aim was to assess the long-term efficacy, immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine against incident and persistent infection with HPV 16 and HPV 18 and their associated cytological and histological outcomes. METHODS: We did a follow-up study of our multicentre, double-blind, randomised, placebo-controlled trial reported in 2004. We included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine (0.5 mL; n=393) or placebo (n=383). We assessed HPV DNA, using cervical samples, and did yearly cervical cytology assessments. We also studied the long-term immunogenicity and safety of the vaccine. FINDINGS: More than 98% seropositivity was maintained for HPV-16/18 antibodies during the extended follow-up phase. We noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints: incident infection, 96.9% (95% CI 81.3-99.9); persistent infection: 6 month definition, 94.3 (63.2-99.9); 12 month definition, 100% (33.6-100). In a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100% (42.4-100) against cervical intraepithelial neoplasia (CIN) lesions associated with vaccine types. We noted broad protection against cytohistological outcomes beyond that anticipated for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31. The vaccine has a good long-term safety profile. INTERPRETATION: Up to 4.5 years, the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe, and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions. There is also evidence of cross protection.

Adult↗

PubMed2002

Cloning, expression and immunization of the new antigen gene Sj-Ts4 of Schistosoma japonicum.

In order to explore the molecular mechanism of high immune protection against schistosomes infection in animals infected with Trichinella spiralis, and to provide several cross-protective antigen genes for developing anti-schistosomiasis vaccine, a Schistosoma japonicum adult worm cDNA library was immunoscreened using sera taken from mice infected with Trichinella spiralis. Nine positive clones were obtained after 3 rounds of immunoscreening. Among them, Sj-Ts4 represents a novel gene of S. japonicum, which coding for a novel protein of 210 amino acids. The protein has a deduced molecular mass of 23 kD and isoelectric point of 7.72. Sj-Ts4 was expressed as a glutathione-S-transferase (GST) fusion protein by cloning into the prokaryotic expression vector pGEX-5X-3. The recombinant Sj-Ts4 protein (rSj-Ts4) was purified and could be recognized by sera of mice infected with S.japonicum. Vaccination of several groups of mice with rSj-Ts4 or rSj-Ts4 incorporated into Freund's complete adjuvant induced high titers of specific IgG antibodies. Two vaccination groups all obtained significant reduction in worm burden (31.36%, 36.80%, P<0.01), compared with the control groups.

Amino Acid Sequence↗

PubMedDate not supplied

Avian Eimeria: effects of gamma irradiation on development of cross-species immunity in foreign and natural host birds.

Repeated inoculation (immunization) of white leghorn chickens with oocysts of the turkey coccidium, Eimeria adenoeides, resulted in significantly improved weight gain and feed-conversion ratios (feed efficiency) after E. tenella challenge. However, the development E. tenella in the immunized chickens did not differ markedly from that in unimmunized chickens, and intestinal lesions remained severe (greater than 3.0). Apparently improved weight gain and feed efficiency can be maintained in the presence of extensive parasite development. The ability to elicit cross-protective immunity was abrogated when the E. adenoeides oocysts were exposed to 15 kRad of gamma irradiation before inoculation into the chickens. Sporozoites existing from irradiated oocysts of E. acervulina also failed to immunize the chickens against challenge with E. tenella but protected chickens almost completely against homologous challenge with E. acervulina. The results indicate that cross-species immunity is not elicited by all developmentally arrested sporozoites and that the ability to produce cross-species immunity can be destroyed by gamma irradiation of the immunizing species.

Animals↗

PubMed1976

Laboratory trials with inactivated vaccines against Escherichia coli (O78 K80) infection in fowls.

Laboratory trials made with five inactivated (O78 K80) Escherichia coli vaccines showed that the greatest degree of protection against an intramuscular challenge with the homologous strain was obtained with an alum precipitated vaccine. This vaccine was equally effective when administered by the subcutaneous, intramuscular or intraperitoneal route. Maximal protection, persisting for at least six weeks, was obtained by inoculating chicks at three weeks of age with a dose of approximately 1-5 X 10(9) cells in 0.5 ml. Some degree of protection was obtained, however, in chicks vaccinated earlier. There was no evidence that this vaccine provided any cross protection against other pathogenic serotypes of E coli. No adverse effect was noted on growth rate or carcase quality in the chicks vaccinated. Immunological studies showed that protection was not related to the production of O and K serum agglutinins.

Age Factors↗