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This phase I clinical trial was designed to determine the feasibility of using rBCG as a live bacterial vaccine vector for the outer surface protein A (OspA) of Borrelia burgdorferi and as model for other vaccines based on a rBCG vector. To construct the vaccine, a signal peptide derived from a mycobacterial lipoprotein was used to direct the export, and membrane-associated surface expression, of...
The protein sequences of the IgA1 protease, TbpA and TbpB proteins differ between meningococci representative of serogroup A, subgroup IV-1 from epidemic disease in The Gambia and serogroup C, ET-37 complex from endemic disease in Mali. The uniformity of restriction endonuclease sites was determined for the iga, tbpA and tbpB genes among strains of both clonal lineages. Rare isolates had acquired...
We have used spring powered jet injectors to deliver a solution of a naked DNA vaccine encoding the influenza hemagglutinin HA into the skin of mice and monkeys. We compared the immune responses induced by this needleless injection technique into the skin to the responses induced by a classical i.m. immunization. Both routes of immunization induced significant ELISA antibody titers and hemagglutination...
Adjuvants are compounds that, when combined with an antigen, potentiate an immune response in an immunized species. There are numerous pathogens for which there are no protective vaccines and since alum is the only adjuvant licensed for use in humans, there is a clear need for more effective adjuvant preparations. In this study we describe the immunopotentiating properties of three novel molecular...
We develop an epidemiological model of hepatitis B virus (HBV) in The Gambia in order to investigate the possible patterns of emergence of a vaccine-resistant strain. Under pessimistic assumptions (e.g., the current vaccine provides no cross-immunity against the variant) the model predicts the variant will not become dominant over the wild-type for at least 50 years. Therefore the current low prevalence...
Given that interesting HIV vaccine candidates, including live preparations and DNA plasmids, exist and that the first phase III vaccine (AIDSVAX) testing is due to begin this summer, 1998, in the U.S., adequately addressing trial preparedness is a pressing issue. Despite double-blind randomized controlled clinical trial design, there may be difficulties with interpretation and use of the usual measures...
Using a bipalmitoylated lipopeptide consisting of an ovalbumin helper T-cell epitope covalently linked to an influenza virus cytotoxic T-lymphocyte (CTL) epitope, we addressed possible factors that may be critical for CTL induction. Antigen processing of lipopeptide appears to be required for T-cell induction since there was virtually no in vitro binding of lipopeptide to purified MHC molecules. A...
Ten adult volunteers, with low prevaccination levels of serum IgG antibodies against meningococcal antigens (<1 μg ml -1 ), received three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine intramuscularly at weeks 0, 6 and 46. Anti-OMV IgG subclass responses were measured and compared with serum bactericidal activity (SBA) and opsonic activity against...
Two antigens comprising either concentrated culture filtrate containing the plasminogen activator, PauA (total antigen) or the same preparation from which PauA had been selectively removed by incubation with a PauA-specific monoclonal antibody and immobilisation on Protein-G agarose (depleted antigen) were combined with either Freund's incomplete adjuvant (FIA) or a commercially used adjuvant (SB62)...
We analyzed data from a randomized trial of AIK-C, high-titre (EZ-H) or medium-titre EZ (EZ-M) vaccines in 3.5 and 6 month old infants in Kinshasa, Zaire, in which the occurrence of rhinorrhoea, cough, diarrhoea, fever, conjunctivitis or rash was monitored for 15 days post-vaccination (including the day of vaccination, day 0). We compared sero-response at 6 weeks and 6 months post-vaccination among...
Caseous lymphadenitis (CLA) is an economically significant disease of sheep caused by the Gram-positive bacterium Corynebacterium pseudotuberculosis. CLA vaccines are currently formulated using formalin inactivated culture supernatants that are rich in the C. pseudotuberculosis phospholipase D (PLD) exotoxin. One alternative to chemical detoxification is to inactivate the PLD genetically. This procedure...
Several recombinant vaccinia viruses are currently being evaluated to induce antigen-specific immunity to a variety of infectious disease agents and tumor associated antigens. T-cell costimulation is extremely important in enhancing T-cell responses, and recombinant vaccines have now been shown to be effective vectors to express a range of these molecules. Both combination vaccines (an admixture of...
The immunity levels against diphtheria, tetanus and poliomyelitis were investigated among blood donors (n=2079) in Berlin. Of all participants, only 60% had full, long-term protection against diphtheria, 72% against tetanus, 87% against poliomyelitis type 1, 77% against poliomyelitis type 2 and 73% against type 3. There was a striking decrease of tetanus and diphtheria immunity levels by age. Immunity...
This study assessed the frequency of symptomatic and asymptomatic primary and secondary infections with rotavirus in children under 24 months and determined protection against symptomatic illness afforded by rhesus and human-rhesus rotavirus reassortant vaccines. Successive cohorts of children (n=236) were followed through five winter rotavirus seasons with cultures of each reported episode of diarrheal...
We have previously shown that intraperitoneal immunization of BALB/c mice with the 14 amino-acid long synthetic peptides G/174-187 and BG/174-187, representing the region 174-187 of the G-glycoprotein from human (H) and bovine (B) respiratory syncytial virus (RSV), respectively, completely protects animals from infection with the corresponding virus. A current goal in vaccine development being the...
Pasteurella multocida major outer membrane protein (OmpH) has been previously characterized as a porin. The native OmpH from strain X-73 (serotype 1) but not recombinant protein from Escherichia coli induced homologous protection in chickens. In this study OmpH sequences from 15 P. multocida serotypes as well as the CU vaccine strain were compared by sequence alignment and revealed high homology,...
Antiviral vaccines are needed for fish. 50μg plasmid DNA in saline by the intramuscular route and 10μg β-gal protein in a commercial oil adjuvant by the peritoneal route induced serum antibody of the same titre and avidity in goldfish. The DNA expressed β-gal under control of the immediate early promoter/enhancer gene of human cytomegalovirus. Commercial bacterin vaccines are administered to fish...
In order to design optimized DNA vectors as genetic vaccines against infections with the hepatitis B virus (HBV) we investigated if secretion or retention of the viral antigens has an influence on the quality and quantity of the humoral immune response. Intramuscular injection of plasmid DNA encoding the HBV large L envelope protein, known to be retained within host cells, induced only a weak response...
The pathogenic characteristics of tick-borne encephalitis (TBE) virus strain (Oshima 5-10) isolated from a sentinel dog in Hokkaido, Japan, was compared by use of a mouse model with several inoculation routes to other strains of TBE virus (the Far Eastern subtype; Sofjin strain and the Western subtype; Hochosterwitz strain) and TBE complex virus (Langat virus; TP-21 strain). The degree of neuroinvasiveness...
Cytokines are powerful regulators of the immune response. In this study, an HIV-1 envelope DNA vaccine and interleukin 15 (IL-15) expression plasmid were intranasally administered to mice. A significant increase in the HIV-1-specific DTH response and CTL activity, and decrease in the serum IgG1/IgG2a ratio was observed in the group which received DNA vaccine and IL-15 expression plasmid compared to...
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