Untitled

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.

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…However, using live organisms for vaccines has drawbacks, as growing and purifying Chlamydia on a large scale are extremely complex. Moreover, these vaccines need cold storage, and even more importantly, there is the potential for avirulent strains to revert back to infectious wild-type strains (154). Because of the safety issues of live vaccines, research switched to organisms that were heat or chemically inactivated.…”

Surface Display of N-Terminally Anchored Invasin by Lactobacillus plantarum Activates NF-κB in Monocytes

“…Promising results have been obtained with mucosal delivery of vaccine antigens through the intranasal, oral, or genital mucosal surfaces by both commensal and attenuated pathogenic bacteria (62). There has been much focus on vaccine delivery by attenuated pathogenic bacteria because of their intrinsic immunostimulatory properties, but such strains could potentially regain their virulence and, also, confer a risk to immunocompromised individuals (18). While commensal strains are considered a safer alternative, they may lack the potentially beneficial immunostimulatory properties of pathogens.…”

Bacillus subtilis

“…These T regulatory cells (TGF-β producing cells, IL-4 and IL-10 producing Th2) inhibit the generation of effector cells, and suppress disease by releasing antigen nonspecific cytokines, thereby resulting in systemic hypo-responsiveness. [29][30][31] Our own results 6,32 suggested that oral administration is an ineffective way to deliver B. subtilis tetanus toxin fragment C (TTFC) vaccine strains, as we were unable to achieve reproducible protective immunity with this approach, even with 9-12 doses of spores or cells at . 10 10 per inoculation in mice or piglets.…”

“…40,41 In yet another study, SL immunization was found to induce vaccine-specific antibody and T-cell responses in the genital tract and, after SL immunization with human papillomavirus (HPV)-like particles, protection against genital HPV infection, indicating the potential of SL immunization to stimulate immune responses also in non-respiratory mucosal tissues. 42 Notably, in contrast to the IN route, either inactivated or live influenza virus did not migrate to or replicate in the CNS, after SL administration. 41 In our studies, we were able to demonstrate that sublingual administration of tetanus vaccine was effective in inducing a robust protective immune response against tetanus toxin challenge.…”