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Results for “Preclinical immunogenicity evaluation”

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At least 163 records · Page 9Linked to original sources
PubMed1999

A randomized trial of conjugated group B streptococcal type Ia vaccine in a rabbit model of ascending infection.

OBJECTIVE: Maternal vaccination may become a central strategy in the prevention of early-onset group B Streptococcal sepsis. Unlike earlier group B streptococcal polysaccharide vaccines that were poorly immunogenic, newer vaccines conjugated to tetanus toxoid have been developed and have improved immunogenicity. We sought to evaluate a conjugated vaccine using our rabbit model of ascending infection. STUDY DESIGN: Rabbit does were randomized to receive either conjugated group B streptococcal type Ia (Ia-tetanus toxoid) or conjugated group B streptococcal type III (III-tetanus toxoid) vaccine. Does were vaccinated 7 days before conception and 7 and 21 days after conception. On days 28 to 30 of a 30-day gestation, does were inoculated intracervically with 10(6) colony-forming units of type Ia group B Streptococcus. Labor was induced if does were undelivered after 72 hours. Does were observed up to 7 days after inoculation. Offspring were observed up to 4 days. We obtained maternal cultures from the uterus, peritoneum, and blood and offspring cultures from the mouth, anus, and blood. Antibody levels were also determined. RESULTS: Offspring survival was significantly improved in the group receiving Ia-tetanus toxoid (P =.047). Outcomes such as maternal sepsis and severe illness, although not reaching statistical significance, showed a trend toward improved outcomes in the Ia-tetanus toxoid group. CONCLUSIONS: This is the first study to evaluate the conjugated group B streptococcal vaccine by using any model of ascending infection. The Ia-tetanus toxoid vaccine led to improved survival and was immunogenic but fell short of its expected efficacy in preventing ascending group B streptococcal disease under these experimental conditions.

Animals↗
PubMed1994

Immunogenic and antigenic properties of a heptavalent high-molecular-weight O-polysaccharide vaccine derived from Pseudomonas aeruginosa.

We investigated the chemical and immunologic properties of a heptavalent vaccine composed of high-molecular-weight polymers of the lipopolysaccharide (LPS) O polysaccharides representative of the most common clinical isolates of Pseudomonas aeruginosa. We also evaluated the serum antibody response to nonvaccine strains of P. aeruginosa, including strains expressing structural variants (subtype strains) of the O side chain of the vaccine strains. The polyvalent vaccine, prepared under conditions suitable for human use, contained low levels of contaminants and passed preclinical safety and toxicity tests required for human use. Chemical analyses indicated that individual polysaccharides were composed of both O-side chain and core sugars. Following immunization of C3H/HeN mice and New Zealand White rabbits, antibody titers against vaccine components increased between 32- and 200-fold. Antibodies reactive with LPS isolated from smooth and rough nonvaccine strains were also elicited. Analysis of the opsonic activity against the known LPS subtype variants of the vaccine strains revealed a variable pattern of killing, which ranged from opsonic killing of > or = 69% of bacterial cells representing all subtype variants within a serogroup to opsonization of only a minority of the subtype variant strains. Mouse and rabbit immune sera showed different patterns of opsonic activity against subtype strains, indicating that different epitopes on these antigens are immunodominant in the representatives of these two animal species tested. The polyvalent vaccine was effective at eliciting antibodies to vaccine components in mice and rabbits, but it remains to be determined if the current heptavalent formulation contains sufficient components to provoke human antibodies reactive with a majority of clinical strains of P. aeruginosa.

Animals↗
PubMed2001

Preclinical and therapeutic utility of HVJ liposomes as a gene transfer vector for hepatocellular carcinoma using herpes simplex virus thymidine kinase.

Although gene therapy has been suggested to be a novel strategy to treat hepatocellular carcinoma (HCC), no study showing the clinical feasibility of vectors to treat HCC has been reported. In this preclinical study, we show evidence indicating that hemagglutinating virus of Japan (HVJ) liposomes are a feasible vector to treat HCC in a clinical setting using ganciclovir (GCV) and herpes simplex virus thymidine kinase (HSV-tk), which is driven by the cytomegalovirus immediate early enhancer/promoter (plasmid pcDNA3/HSV-tk). In in vitro experiments, almost complete tumor cell regression was achieved with the optimal GCV concentration (100 microg/mL) and more than 1/3 regression was seen even with a 20% transduction ratio using HuH7 HCC cells stably transformed by HSV-tk. HVJ liposomes showed a 19.7% (mean) transduction rate of the lacZ gene in a relatively large mass of more than 300 mm3 in vivo, which is a clinically detectable size, implanted into SCID mice. Moreover, a single HSV-tk injection of HVJ liposomes followed by GCV treatment inhibited tumor growth at least within a week, and repeat administration was more effective. Furthermore, subcutaneous injection of an HVJ liposomes vehicle induced no apparent inflammatory response in C3H/HeN mice, whereas lacZ gene transfection resulted in inflammatory pathology, suggesting a lower immunogenicity of the HVJ envelope protein than those of bacteria-derived plasmid DNA or the beta-galactosidase gene product. From these findings, we conclude that HVJ liposomes are a clinically safe and effective gene transfer vector to treat HCC.

Animals↗
PubMed1995

An anti-murine CD3 monoclonal antibody with a low affinity for Fc gamma receptors suppresses transplantation responses while minimizing acute toxicity and immunogenicity.

145-2C11, a hamster mAb directed against the mouse CD3 complex, is a potent immunosuppressive agent. Upon initial treatment, 145-2C11 triggers a systemic release of multiple cytokines that is responsible for the acute toxicity of the mAb. This cellular activation is a consequence of the cross-linking between T lymphocytes and Fc gamma R-bearing cells, mediated by the high affinity of the hamster mAb for murine Fc gamma Rs. Repeated mAb injections result in the onset of a neutralizing humoral response. Therefore, there has been an increased interest in developing nonmitogenic forms of anti-CD3 mAbs, although it is not clear whether these Abs will retain immunosuppressive properties. To determine whether the initial cytokine production is necessary for the immunosuppressive properties and the immunogenicity of anti-CD3 mAbs in vivo, we have generated chimeric (hamster 145-2C11 F(ab')2 region/mouse Fc gamma portion) mAbs using murine isotypes with different affinities for Fc gamma Rs. The 145-2C11 and a chimeric IgG2a isotype, both of which bind murine Fc gamma Rs avidly, had similar activating, immunogenic, and immunosuppressive properties in mice. The administration of a chimeric IgG3 isotype with a very low affinity for murine Fc gamma Rs did not result in cytokine production, a humoral response against the mAb, or TCR desensitization. Nevertheless, prolongation of skin graft survival was similar in the IgG3, IgG2a, and 145-2C11-treated mice, indicating that Fc gamma R nonbinding anti-CD3 mAbs retain potent immunosuppressive properties in vivo while not being immunogenic. This enhanced therapeutic to toxic profile may be beneficial in clinical transplantation.

Amino Acid Sequence↗
PubMed1999

Technology evaluation: DISC.

Cantab is developing its DISC technology as a potential gene therapy product for cancer (DISC-Onc) and neurological and blood disorders (DISC-GT). Clinical trials are expected to commence in early 1999 [296831]. The DISC technology utilizes a herpes virus that has had a gene removed to prevent it from replicating [250526]. Phase I trials in leukemia were scheduled to commence in 1998 [250526], however, it was decided that although DISC-Onc is capable of carrying genes into leukemic cells, the levels of immunomodulator genes did not meet the target initially set for the commencement of trials. Hence, Cantab turned its attention to other cancers, and hoped to identify an alternative target for phase I trials in the first half of 1998 [279798]. Additional preclinical work using a murine version of the lead construct produced a significant therapeutic effect in animal tumor models [289716]. DISC-Onc is envisaged to deliver immunogenic genes such as cytokine or stimulatory protein genes [275129]. Cantab, in collaboration with Nottingham Trent University and Birmingham University, has shown that the DISC-Onc has delivered genes effectively to human colorectal, gastric and ovarian cancer tumors. Transfection rates have been shown to be favorable and have been proven to be at least as good as, if not better than, other vectors [279798]. Also, DISC-Onc carrying a functional GM-CSF, has antitumor activity in mouse models of renal cancer and leukemia [250526], [261768]. The DISC Neurology technology (DISC-GT), for gene therapy of neurological disease, is being developed in collaboration with Cambridge University, and enables HSV-driven long-term gene expression in nerve cells [279798].

Biotechnology↗
PubMed2004

Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys.

A universal influenza virus vaccine that does not require frequent updates and/or annual immunizations will offer significant advantages over current seasonal flu vaccines. The highly conserved influenza virus A M2 membrane protein has been previously suggested as a potential antigen target for such a vaccine. Here, we report systematic evaluation of M2 peptide conjugate vaccines (synthetic peptides of M2 extracellular domain conjugated to keyhole limpet hemocyanin (KLH) or Neisseria meningitidis outer membrane protein complex (OMPC)) in mice, ferrets, and rhesus monkeys. The conjugate vaccines were highly immunogenic in all species tested and were able to confer both protection against lethal challenge of either H1N1 or H3N1 virus in mice and reduce viral shedding in the lower respiratory tracts of mice and ferrets. The protection against lethal challenge in mice could also be achieved by passive transfer of monkey sera containing high M2 antibody titers. In addition, we showed that M2 antisera were cross reactive with M2 peptides derived from a wide range of human influenza A strains, but they failed to react with M2 peptides of the pathogenic H5N1 virus (A/Hong Kong/97). The data presented here will permit better understanding of the potential of an M2-based vaccine approach.

Amino Acid Sequence↗
PubMed1986

Evaluation of a new Rift Valley fever vaccine: safety and immunogenicity trials.

A formalin-inactivated Rift Valley fever vaccine prepared in primary monkey kidney cells has been used to protect laboratory workers from disease since 1967. A similar but improved vaccine was prepared in 1978-1979 using well characterized diploid fetal rhesus lung cells. In initial clinical trials reported here, the new vaccine elicited high levels of plaque neutralizing antibodies and caused only minimal local reactions at the injection site. Significant variability was observed in the geometric mean titre evoked by various vaccine lots. This variability had not been predicted by conventional pre-filtration or pre-inactivation virus infectivity assays, or the results of animal potency tests. These findings emphasize the need for statistically valid human potency testing and the development of accurate predictive preclinical measurements for this and other vaccines.

Adult↗
PubMed1981

[An oral enteritis-vaccine composed of twelve heat-inactivated Enterobacteriaceae 3. Communication: studies on efficacy tests in mice protection tests (author's transl)].

The polyvalent vaccine consists of twelve heat-inactivated species of Enterobacteriaceae (six strains of Salmonellae, two strains of Shigellae, four strains of Dyspepsia coli). The above vaccine is administered orally (6) to man for prophylactic purposes against local infections. The present communication describes the efficacy results of the vaccine obtained for different parameters by the mouse protection test. For this purpose, seven different infection models were used: oral infection with a strain of S. typhimurium and a strain of S. enteritidis, respectively, and intraperitoneal infection with the following five strains: S.l typhimurium, S. panama, S. enteritidis, Sh. flexneri 2a, or E. coli 2380. For 10 days the mice were daily immunized with the twelve-fold vaccine orally administered by means of a probang. On the 10th day after the last orally applied antigen, the animals were challenged with the seven strains mentioned above. The success of vaccination was determined by the difference of mortality between vaccinated and non-vaccinated mice. The results show (Table 1) following the vaccination that a significant effect could be observed and statistically be evaluated for 6 models of infection. Optimal values showing the highest consistency rate were found for the model of intraperitoneal infection with the strain of E. coli 2380. Which is why, studies were made for the following parameters by using the latter mode of infection. The efficacy of the oral immunization depends on the dosage of the vaccine (Table 2). Even at a dilution of 1 : 1000, the effect of the vaccine was still sufficient. Only a dilution of 1 : 10 000 made the vaccination almost ineffective. - The content of humidity of the lyophilized vaccine in a range of 4% to 12% did not influence the immunogenicity (Table 3). - The protection obtained by vaccination was found to last unexpectedly long. The vaccinated mice were still well protected even one year after the oral vaccination (Table 4), which means - when referred to the life-span of mice - that protection is effected for almost a life-time. The lyophilized vaccine does not even loose its immunogenicity after storage at 22 degrees C and 40 degrees C over a period of 3 years (Table 5). These polyvalent lyophilized vaccine are, therefore, storable even under tropical conditions without cooling. This is a further great advantage of this vaccine.

Administration, Oral↗
PubMed1993

In vitro potency assays for nonreplicating veterinary vaccines: comparison to in vivo assays and considerations in assay development.

Each finished batch or serial of veterinary vaccine must be potency tested to assure the quality of marketed product. The potency assay must be correlated to efficacy in the target species. Potency assays of nonreplicating vaccines have traditionally measured the immune response to the vaccine in host or laboratory animals by serology or protection from challenge. Such tests are expensive, time-consuming, and raise animal welfare concerns. As disease agent protective antigens are described, in vitro techniques for quantitating them can be applied to vaccine potency measurement. However, in many cases the immunological adjuvants critical to the efficacy of the biological interfere with in vitro antigen quantitation techniques. The development of techniques that remove or compensate for the effect of adjuvants on the assays, sham vaccines containing no antigen, reference preparations containing a proven protective immunogen dose, characterization of the immunological reactants, and appropriate design and data analysis have contributed to the development of rapid, reproducible, humane, and relatively inexpensive in vitro potency assays to be used in the evaluation of veterinary biologicals.

Animal Testing Alternatives↗
PubMed2005

Development of V2-deleted trimeric envelope vaccine candidates from human immunodeficiency virus type 1 (HIV-1) subtypes B and C.

The urgent need for a vaccine against HIV/AIDS requires that multiple strategies be employed and evaluated in a clinical setting. V2-loop deleted trimeric envelope (Env) immunogens (protein and DNA) from subtypes B and C human immunodeficiency virus type 1 (HIV-1) strains were produced for ongoing and future clinical evaluations with other HIV antigens, adjuvants and deliveries.

AIDS Vaccines↗
PubMed2001

A purified inactivated Japanese encephalitis virus vaccine made in Vero cells.

A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals. The manufacturing process was efficient in generating a high yield of virus, essentially free of contaminating host cell proteins and nucleic acids. The PIV was formulated with aluminum hydroxide and administered to mice by subcutaneous inoculation. Vaccinated animals developed high-titered JE virus neutralizing antibodies in a dose dependent fashion after two injections. The vaccine protected mice against morbidity and mortality after challenge with live, virulent, JE virus. Compared with the existing licensed mouse brain-derived vaccine, JE-Vax, the Vero cell-derived JE-PIV was more immunogenic and as effective as preventing encephalitis in mice. The JE-PIV is currently being tested for safety and immunogenicity in volunteers.

Animals↗
PubMed2005

Vaccine prospects for amebiasis.

Entamoeba histolytica is a eukaryotic protozoan parasite and is the causative agent of amebic colitis and amebic liver abscess. Many insights into the innate and acquired immune responses to infection with E. histolytica have been made in recent years. These findings have provided a foundation for producing a vaccine that could help to prevent the initial establishment of infection in the intestinal wall. The galactose and N-acetyl-D-galactosamine-specific lectin on the surface of the ameba is an immunodominant molecule that is highly conserved and has an integral role in the stimulation of these immune responses. The structure of the lectin has been defined, and the heavy subunit with its cysteine-rich region has been demonstrated in animal models to have some efficacy as a possible vaccine agent for prevention of amebic infection. Finding an ideal animal model of amebic intestinal infection has been difficult, but the C3H mouse and severe combined immunodeficient mouse-human intestinal xenograft models have both provided valuable insights into the first line of immune defense at the mucosal wall of the colon. Providing safe food and water to all people in the developing world is a formidable task that is not achievable in the foreseeable future. However, a vaccine for amebiasis could make a significant impact on the morbidity and mortality from the disease. Many components of the ameba are immunogenic and may serve as targets for a future vaccine, including the galactose and N-acetyl-D-galactosamine lectin, the serine-rich E. histolytica protein, cysteine proteinases, lipophosphoglycans, amebapores and the 29-kDa protein.

Amebiasis↗
PubMedDate not supplied

[Immunogenicity and protective capacity of leptospiral whole-cell monovalent serogroup Ballum vaccines in hamsters].

Leptospira serogroup Ballum is at present the first cause of human leptospirosis in Cuba. Killed whole-cell vaccines were formulated with two clinical isolates of Leptospira interrogans serogroup Ballum using aluminum hydroxide as adjuvant. Agglutinins levels induced by each vaccine in hamsters were estimated by microscopic agglutination test and specific IgG activities were quantified by a whole cell-based enzyme-linked immunosorbent assay. Homologous and cross protective capacity against lethal and sublethal infection were determined in vaccinated animals by challenge with 100 and 10,000 LD50 of five virulent strains belonging to serogroups Ballum, Canicola, Icterohaemorrhagiae and Pomona. Both monovalent serogroup Ballum vaccines were immunogenic and induced complete homologous protection in the animal model. Cross-protection was only significant in one of the two vaccines against challenge with 100 LD50 of serogroup Canicola. The results of this study demonstrate the high immunogenicity and protective capacity in hamsters of whole-cell monovalent vaccines formulated with two vaccine candidate strains belonging to the most prevalent serogroup of Leptospira in Cuba.

Animals↗
PubMedDate not supplied

[House-dust mites allergen for specific immunotherapy by oral administration: experimental study].

The oral medicinal form of house-dust allergen has been prepared with the use of new technology. To produce the preparation, the standard water-saline extract obtained from house-dust mites (Dermatophagoides farinae) allergen has been used. This preparation is chemically stable and does not lose its biological activity for 2 - 3 years of storage. The microbiological purity of the allergen meets the requirements for oral preparations. The allergen has proved to be safe in cases of prolonged administration and has no chronic toxicity. As shown with the use of immunochemical methods, the preparation has high immunogenicity and lower allergenicity. This preparation may be recommended for clinical trials on a limited circle of subjects.

Administration, Oral↗
PubMed2004

Suppression and modulation of cellular and humoral immune responses to Haemophilus influenzae type B (Hib) conjugate vaccine in hib-diphtheria-tetanus toxoids-acellular pertussis combination vaccines: a study in a rat model.

We assessed a rat model to evaluate the immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines and the effect on Hib immunogenicity of combining 2 Hib vaccines (Hib-tetanus toxoid [TT]-A and Hib-TT-B) with diphtheria-TT-acellular pertussis (DTaP)(3) or DTaP(5)/inactivated poliovirus (IPV) vaccines. Rats were immunized subcutaneously with Hib alone or with Hib and DTaP-based vaccines; anti-Hib capsular polysaccharide IgG, poly-ribosyl-ribitol-phosphate (PRP), IgG subclass, and cellular immune responses were evaluated. Results showed a significant reduction in the antibody response to PRP when Hib-TT-A was administered in combination with DTaP(3) and showed changes in the anti-PRP IgG subclass distribution between the separate and combination groups. However, combining Hib-TT-B with DTaP(5)/IPV did not reduce the anti-PRP antibody response. These results suggest that the model can predict the effect of combined administration of Hib and DTaP vaccines on Hib immunogenicity and would be suitable for preclinical studies of mechanisms of interference in Hib/DTaP vaccines.

Animals↗
PubMed1985

[Experiments to produce an attenuated strain of the transmissible gastroenteritis virus and its use as a live vaccine].

Serial passages have been performed of a field virus of the transmissive gastroenteritis to obtain an attenuated strain adapted to a permanent cell line of pig kidney, "SPEV". The strain is innocuous for test animals, for pigs of all ages, and for swine during the entire period of pregnancy. It has proved genetically stable. The strain is immunogenic for swine and pigs both under laboratory and under field conditions (in new foci and on stationary farms) and can be used as a live vaccine against transmissive gastroenteritis, either untreated or in a freeze-dried state.

Animals↗
PubMed1986

[Effect of blastolysin on the development of specific immunity to whooping cough].

The influence of blastolysin, the cell-wall glycopeptide of Lactobacillus bulgaricus, on the main immunobiological properties of pertussis vaccine, its immunogenicity and toxicity, has been studied. The use of blastolysin, introduced as a stimulating agent in definite doses and following definite administration schedules, has been shown to permit achieving not only an increase in the immunogenicity of the corpuscular pertussis vaccine, but also a considerable decrease in its toxicity and histamine-sensitizing activity.

Adjuvants, Immunologic↗