Dataset of service life data for 100 building elements and technical systems including their descriptive statistics and fitting to lognormal distribution.

This article presents the descriptive statistics of service life data of building elements, gathered through an international, European and Swiss literature review of LCA, LCC and other sources called "Real-Estate Management sources" that include building owners, banks, insurances, associations of tenants and owners, etc. Furthermore, the properties of the fitted lognormal distribution are given. The data are structured, using a hybrid decomposition (functional decomposition, according to the eBKP-H - SN506511 and material decomposition, as well). These data and the derived statistical distributions were used in a research study, in order to quantify the uncertainty and sensitivity of the LCA and LCC output, due to the variability of the building elements' service lives.

Expression and morphology of enterotoxigenic Escherichia coli surface antigen CS31A in E. coli K12 and Vibrio cholerae.

Enterotoxigenic Escherichia coli (ETEC) is known as a worldwide cause of diarrheal disease. The pathogenesis involves the attachment of the microorganisms to the mucosa and the production of enterotoxins. Surface expression of CS31A fimbriae was assessed by Western blots, dot blots, immunofluorescence, and electron microscopy using negative staining and immunogold labeling. These investigations revealed significant differences in both the morphology of the wild-type and recombinant strains and the antigen exposure of CS31A in the wild-type and recombinant strains. In the wild-type ETEC strain, expression of CS31A was subject to phase variation. The recombinant E. coli strain produced CS31A but was prone to epitope shedding. In Vibrio cholerae vaccine strain CVD 103-HgR, the recombinant CS31A antigen was expressed but was only found intracellularly. Thus, E. coli strains seem to lend themselves better to the development of recombinant vaccines expressing ETEC-specific antigens at the cell's surface than strains from other orders or genera such as V. cholerae.

Morphological and immunocytochemical analysis of Escherichia coli-specific surface antigens in wildtype strains and in recombinant Vibrio cholerae.

Adhesion is the first step in the pathogenesis of enterotoxigenic Escherichia coli infections. The genes encoding the most prevalent adhesion factors CFA/I, CS3 and CS6 were cloned into Vibrio cholerae strain CVD 103-HgR and expression of fimbriae was investigated in wildtype and recombinant strains by transmission electron microscopy in conjunction with immunolabelling and negative staining. Negative staining was effective in revealing CFA/I and CS3, but not CS6. Although morphology of fimbriae differed between wildtype and recombinant strains, corresponding surface antigens were recognized by specific antibodies. The present study provides evidence that ETEC-specific fimbriae can adequately be expressed in an attenuated V. cholerae vaccine strain and that immunoelectron microscopy is a critical tool to validate the surface expression of antigens in view of their possible suitability for recombinant vaccines.

Expression of enterotoxigenic Escherichia coli colonization factors in Vibrio cholerae.

As a first step towards a vaccine against diarrhoeal disease caused by enterotoxigenic Escherichia coli (ETEC), we have studied the expression of several ETEC antigens in the live attenuated Vibrio cholerae vaccine strain CVD 103-HgR. Colonization factors (CF) CFA/I, CS3, and CS6 were expressed at the surface of V. cholerae CVD 103-HgR. Both CFA/I and CS3 required the co-expression of a positive regulator for expression, while CS6 was expressed without regulation. Up-regulation of CF expression in V. cholerae was very efficient, so that high amounts of CFA/I and CS3 similar to those in wild-type ETEC were synthesized from chromosomally integrated CF and positive regulator loci. Increasing either the operon and/or the positive regulator gene dosage resulted in only a small increase in CFA/I and CS3 expression. In contrast, the level of expression of the non-regulated CS6 fimbriae appeared to be more dependent on gene dosage. While CF expression in wild-type ETEC is known to be tightly thermoregulated and medium dependent, it seems to be less stringent in V. cholerae. Finally, co-expression of two or three CFs in the same strain was efficient even under the control of one single regulator gene.

Assessing the expression of enterotoxigenic Escherichia coli-specific surface antigens in recombinant strains by transmission electron microscopy and immunolabeling.

Infections with enterotoxigenic Escherichia coli (ETEC) are a major cause of travelers' diarrhea worldwide. Colonization of the small intestine mucosa is dependent on specific colonization factor antigens (CFA) and coli surface (CS) antigens. CFA/1, CS3, and CS6 are the most prevalent fimbrial antigens found in clinical isolates. The goal of our study was to visualize the morphology of CS3 and CS6 fimbriae in wild-type and recombinant E. coli strains by means of transmission electron microscopy in conjunction with negative staining and immunolabeling. Corresponding ETEC genes were cloned into E. coli K12 strain DH10B. Expression of fimbriae was dependent on culture conditions and sample handling. Specific immunolabeling of fimbriae unequivocally demonstrated the presence of all types of surface antigens investigated. Negative staining was effective in revealing CS3 but not CS6. In addition, this technique clearly demonstrated differences in the morphology of genetically and immunologically identical CS3 surface antigens in wild-type and recombinant strains. This paper provides a basis for the assessment of recombinant vaccines.

Vaccines against typhoid fever.

Because of high infectivity and significant disease burden, typhoid fever constitutes a major global health problem. Implementation of adequate food handling practices and establishment of safe water supplies are the cornerstone for the development of an effective prevention program. However, vaccination against typhoid fever remains an essential tool for the effective management of this disease. Currently, there are two well tolerated and effective licensed vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen and can be administered either intramuscularly or subcutaneously and the other is based on the use of live attenuated bacteria for oral administration. The advantages and disadvantages of the various approaches taken in the development of a vaccine against typhoid fever are discussed, along with the potential for future vaccine candidates.

Biosafety evaluation of recombinant live oral bacterial vaccines in the context of European regulation.

Live bacterial vaccines represent a highly valid preventive strategy in the fight against infectious disease. However, the road from research to market is peppered with hurdles, one of which is the requirement for high biosafety characteristics, which the candidate vaccine has to display. In Europe, the European Agency for the evaluation of medicinal products (EMEA) is the relevant authority regulating the licensure of genetically engineered vaccines. For this purpose, the agency may rely on several directives and guidelines defined in the past 15 years. As for live vaccines containing genetically modified organisms (GMOs) susceptible to be released into the environment, Directive 2001/18/EC determines the framework and principles of an environmental risk assessment (ERA) process, the results of which constitute an important section of the vaccine registration package submitted to registration authorities. In this article, we address the implications of current European regulations for the approval of live oral bacterial vaccines with emphasis on the assessment of potential risks associated with environmental release. Biosafety aspects of already registered and some promising live bacterial vaccine strains will be briefly discussed.

Immunogenicity and safety of BERNA-YF compared with two other 17D yellow fever vaccines in a phase 3 clinical trial.

BERNA-YF (Flavimun) is a live, attenuated yellow fever (YF) vaccine of the 17D strain produced by Berna Biotech Ltd. following a transfer of technology from the Robert Koch Institute (RKI) in Berlin, Germany. In this phase 3 bridging study, the immunogenicity and safety of BERNA-YF were compared with the original RKI YF vaccine (RKI-YF) and to a current, commercially available YF vaccine, Stamaril (AP-YF; Aventis Pasteur, Lyon, France), in 304 healthy, adult volunteers. All three vaccines elicited an effective immune response with seroprotection achieved in 100% of individuals in each vaccine group at a neutralizing antibody titer > or = 1:10. BERNA-YF was shown to be comparable to the other two vaccine products, and subgroup analysis showed no differences in immune response between three consecutive production batches. The immune response to BERNA-YF and RKI-YF was very similar, with no significant difference in antibody titer between the two groups (P = 0.4634). However, AP-YF vaccination resulted in a significantly lower antibody titer (P < 0.0001 versus BERNA-YF). Males exhibited a higher antibody response than females to both BERNA-YF and RKI-YF, but not to AP-YF. All three vaccines were well tolerated and no serious adverse events were reported.

Biosafety aspects of the recombinant live oral Vibrio cholerae vaccine strain CVD 103-HgR.

The development of live attenuated vaccines, allowing for the safe and effective immunisation at mucosal surfaces, is a strategy of great interest for vaccinologists. The main advantage of this approach over conventional parenteral vaccines is the induction of strong mucosal immune responses, allowing targeting of the pathogen at the initial point of contact with the host. Further advantages include the ease of administration, high acceptance by vaccines, and relatively low production costs. Finally, well-characterised, safe and immunogenic vaccine strains are well suited as vectors for the mucosal delivery of foreign vaccine antigens and of DNA vaccines. However, such vaccines, when based on or containing genetically modified organisms (GMOs), are facing new and specific regulatory hurdles, particularly regarding the potential risks for humans and the environment. In this contribution we address selected aspects of the risk assessment of live attenuated bacterial vaccines covered in the course of the registration of vaccine strain CVD 103-HgR as a recombinant live oral vaccine against cholera.

Vaccines against Infections Caused by Salmonella, Shigella, and Pathogenic Escherichia coli.

Infectious diseases represent one of the most common causes of death worldwide, with the enteropathogenic bacteria Salmonella and Shigella and pathogenic Escherichia coli being among the most detrimental. Currently, vaccination represents the preferred method of preventing such infections. For stimulating the adaptive immune response, immunizations are frequently based on formulations which include inactivated whole-cell vaccines, live attenuated vaccines, or subunit vaccines. These can be administered via a parenteral or mucosal route, the latter having the advantage that it most closely mimics the actual course of infection. In addition to the type of vaccine and method of application, important consideration needs to be paid to safety, efficacy, and cost, which are often major bottlenecks in the successful implementation of vaccines. In this chapter we take a limited look at the history surrounding vaccinations involving Salmonella, Shigella, and pathogenic E. coli. Salmonella infections, which can lead to typhoid fever, are becoming increasing difficult to treat with antibiotics due to multi-drug-resistant strains. At present, the parenteral Vi-based subunit vaccines and the live attenuated oral vaccine Ty21a have proven to be the vaccines of choice, with high levels of protective efficacy and limited side effects. Shigella infections are responsible for the diarrheal disease shigellosis. Various live and nonliving mucosal and parenteral vaccines have been tested, with the most promising candidates evolving around those that stimulate the production of O-antigen-specific antibodies. Pathogenic Escherichia coli infections can lead to severe diseases due to the bacterium's production of several specific toxins. Vaccines against this bacterium target its toxins, as well as surface-exposed antigens, all of which have been found to be effective as immunogens.

Live attenuated bacteria as vectors to deliver plasmid DNA vaccines.

Live attenuated bacterial vaccines allow vaccination via the mucosal surfaces and specific targeting to professional antigen presenting cells located at the inductive sites of the immune system. A novel approach exploits attenuated intracellular bacteria as a delivery system for eukaryotic antigen expression vectors (so-called DNA vaccines). Candidate carrier bacteria include attenuated strains of Salmonella, Shigella and Listeria spp, which have been shown, in vitro, to deliver DNA vaccines to human cells. Bacterial DNA vaccine delivery has also demonstrated in vivo efficacy in several experimental animal models of infectious diseases and tumors. The next step should be the clinical assessment of the safety, immunogenicity and efficacy of DNA vaccine delivery by live bacterial vaccines.