Abstract
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.
Highlights
Live vaccines have played a critical role from the beginning of vaccinology
This opens for the development of new live bacterial vaccines that can avoid the downsides of parenterally administered vaccine because it (i) mimics the route of entry of many pathogens and stimulate the mucosal immune response (ii) can be administered orally or nasally avoiding the risk associated with contaminated needles and need for a professional healthcare infra structure (iii) has a simple down stream processing
Passive immunity has limits in its temporary nature, these results suggest that lactic acid bacteria (LAB) elegantly can be used for the delivery of neutralising antibodies at mucosal sites
Summary
Live vaccines have played a critical role from the beginning of vaccinology. the very first vaccination experiment in the Western world was Jenner's inoculation of a boy with the milder cowpox virus to protect against the deadly smallpox. Due to their safe status and the availability of genetic tools for recombinant gene expression LAB are attractive for use as vaccine vehicles Their non-pathogenic status circumvents the need to construct attenuated mutants. This indicates that the lactobacilli strain expressing Der p1 can suppress the cytokine milieu promoting the Th2 allergic response Another example of the strain specific effect of LAB on induction and maintenance of oral tolerance has been shown using ί-lactoglobulin and gnotobiotic mice [37]. New ways of further attenuating bacteria like combining auxotrophy with deletions of virulence genes [14] may open for the use of live vaccines to immune-compromised hosts. In the future tailor-made vaccines might be the solution for individuals with a genetic profile prone to autoimmunity
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