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At least 19 recordsLinked to original sources

Bacterial vaccine vectors and bacillus Calmette-Guérin.

Recent advances in biotechnology now allow a more modern approach to the development of vaccines, particularly that of recombinant vaccines. Bacterial vaccine vectors have the advantage over viral vectors in that the former have the ability to express a greater number of antigens in different forms. Although no recombinant bacterial vaccines are currently in use, bacillus Calmette-Guérin (BCG), Salmonella species, and Escherichia coli are being developed as vaccine vectors. We review plasmid systems and mutant strains developed for the expression of foreign antigens, with particular emphasis on those developed for BCG. We describe the development of antigen expression systems as well as the immune response elicited by recombinant BCG vaccine strains to bacterial and human immunodeficiency virus (HIV) antigens. A modified recombinant BCG carrier with selection for the stable maintenance of rDNA is proposed.

Administration, Oral↗

Determination of endotoxicity in bacterial vaccines.

Endotoxicity of bacterial vaccines was quantitated in mice by using actinomycin D as potentiating agent. The results were compared with those obtained by the mouse weight gain test. The lethality of Escherichia coli lipopolysaccharide was increased 2,140 times when 12.5 mug of actinomycin D was used. The mean lethal dose values of heated and unheated pertussis vaccines were similar in the actinomycin D enhancement assay, but the unheated vaccine was significantly more toxic in the mouse weight gain test. Acetone-inactivated typhoid vaccine was slightly less toxic than the heat-phenol-inactivated vaccine in both the actinomycin D enhancement assay and mouse weight gain test. Endotoxicity of experimental vaccines prepared by extraction of Pseudomonas aeruginosa strains was high as compared with E. coli lipopolysaccharide. The BALB/c mice were about four times more susceptible than the random bred NIH strain mice. The results indicate that the actinomycin D enhancement assay had the advantages of being more sensitive and probably more specific.

Acetone↗

Plasmid maintenance systems suitable for GMO-based bacterial vaccines.

Live carrier-based bacterial vaccines represent a vaccine strategy that offers exceptional flexibility. Commensal or attenuated strains of pathogenic bacteria can be used as live carriers to present foreign antigens from unrelated pathogens to the immune system, with the aim of eliciting protective immune responses. As for oral immunisation, such an approach obviates the usual loss of antigen integrity observed during gastrointestinal passage and allows the delivery of a sufficient antigen dose to the mucosal immune system. Antibiotic and antibiotic-resistance genes have traditionally been used for the maintenance of recombinant plasmid vectors in bacteria used for biotechnological purposes. However, their continued use may appear undesirable in the field of live carrier-based vaccine development. This review focuses on strategies to omit antibiotic resistance determinants in live bacterial vaccines and discusses several balanced lethal-plasmid stabilisation systems with respect to maintenance of plasmid inheritance and antigenicity of plasmid-encoded antigen in vivo.

Administration, Oral↗

Live bacterial vaccines--a review and identification of potential hazards.

The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.

Journal Article↗

Specific immune response in the respiratory tract after administration of an oral polyvalent bacterial vaccine.

An oral killed polyvalent bacterial vaccine was assessed in a double-blind trial involving healthy volunteers. Three courses of oral vaccine were given over a 2-month period; each course contained 10(10) Haemophilus influenzae and 7 X 10(9) Staphylococcus aureus organisms. Immunity was assessed by monitoring antibody in saliva and serum over a 3-month period. No evidence of a nonspecific effect on immune parameters (immunoglobulin levels and Escherichia coli antibody) was detected in saliva or serum. An increase in H. influenzae antibody in saliva was detected in 55% of subjects receiving the vaccine compared with 6.7% of the placebo group. Antibody was associated with immunoglobulin A (IgA), IgG, and IgM, but the greatest increases over preimmunization levels were detected in the IgA class. No increase in serum antibody levels was detected. Subjects with higher preimmunization levels of salivary antibody to H. influenzae were less likely to respond to the oral bacterial vaccine. No increase in S. aureus antibody was detected in saliva or serum.

Administration, Oral↗

Reasons for instability of bacterial vaccines.

Stability problems in relation to bacterial vaccines vary widely between different types of product. Killed whole cell bacterial vaccines including pertussis, cholera and typhoid vaccines generally show a high degree of stability of potency. Reversion to toxicity may occur in incompletely inactivated pertussis vaccines. Live attenuated vaccines such as BCG and Ty21a typhoid vaccines lose potency through loss of viability when exposed to adverse conditions. Both vaccines are susceptible to ultra violet radiation but Ty21a also has low thermal stability. Its fragility is probably a consequence of multiple mutations affecting structural and metabolic factors. Diphtheria and tetanus toxoids generally show high stability of potency. Reversion to toxicity may occur if the toxoiding process is inadequate. Decline in potency may result from exposure to adverse conditions, such as freezing, that affect the interaction with the adjuvant. Similar problems may be encountered with purified subunit vaccines such as acellular pertussis preparations. Some components, in particular pertussis toxin and filamentous haemagglutinin, show inherent low stability and degrade on storage at refrigerator temperatures unless stabilized by a protein cross-linking agent. Bacterial proteases carried over from the cell cultures may also be responsible for degradation of purified components. Purified bacterial polysaccharides usually show high stability if freeze-dried under appropriate conditions. Catalytic degradation may occur however, if the stabilizers are of inadequate purity. Polysaccharide-protein conjugates such as Haemophilus influenzae b (Hib) polyribosylribityl phosphate-protein conjugates show high thermal stability if freeze dried. In the liquid state, such conjugates tend to degrade by hydrolysis of the polysaccharide chains. Combined vaccines may present special stability problems because of the interaction of the various components in the liquid state. It can be difficult to freeze-dry some components of such vaccines, particularly aluminium hydroxide-adsorbed diphtheria-tetanus-pertussis (DTP) components. Slow release vaccines based on polyglycolide-factolide microspheres may show suboptimal stability of encapsulated antigen under both in vitro conditions as a result of gradual acidification through polymer hydrolysis. Vaccines based on the use of live recombinant strains to express heterologous protective antigens may present special stability problems. Apart from the carrier strains, heterologous genes carried on plasmids may be subject to spontaneous deletion under adverse conditions. These issues have received relatively little attention hitherto but are likely to achieve greater prominence as development of such preparations proceeds.

Amino Acid Sequence↗

Oral bacterial vaccine vectors for the delivery of subunit and nucleic acid vaccines to the organized lymphoid tissue of the intestine.

Bacterial vaccine vectors have the potential to deliver a number of antigens from bacterial, protozoan and viral pathogens. To further develop the utility of bacterial vaccine vectors we are currently evaluating three model systems: 1. A Salmonella-ETEC Vaccine Vector; 2. A Salmonella-HIV Vaccine Vector, and 3. Novel Live Bacterial Nucleic Acid Vaccine Vectors. Through our studies, and those of others, significant progress has been made toward bacterial vaccine vector systems that effectively deliver subunit and nucleic acid vaccines to the organized lymphoid tissue of the intestine. The practical reality of these findings is discussed.

AIDS Vaccines↗

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.

Bacterial Vaccines↗

Proposals for quality control methods of bacterial vaccines for immunostimulation. I. General considerations.

Control methods for this type of vaccines include tests on identity, absence of contaminating microorganisms and safety which are required for any vaccine. In addition, for the control of vaccines for immunostimulation in cancer therapy some special methods for safety and potency testing are required. Some assays are proposed, such as stimulation of lymphocytes in vivo and in vitro, stimulation of macrophages (listeria clearance) in mice and the prophylactic and therapeutic tumor model in mice. Details of these tests are given in the companion papers II and III. The influence of the method of preparation of BCG vaccines on its mode of action in some of these models will be emphasized.

BCG Vaccine↗