Mucosal Lactobacillus vectored vaccines

ArticleinHuman Vaccines & Immunotherapeutics 9(4) · January 2013with6 Reads
DOI: 10.4161/hv.23302 · Source: PubMed
Traditional non-gastrointestinal vaccines can prevent effectively the invasion of pathogens; however, these vaccines are less effective against mucosal infections because there is not a sufficient immune response at the mucosa. Most pathogens invade via a mucosal pathway (oral, intranasal, or vaginal). ( 1) It is widely accepted that Lactobacillus species play a critical role as commensals in the gastrointestinal (GI) tract. ( 2) Their ability to survive in the digestive tract, their close association with the intestinal epithelium, their immunomodulatory properties and their safety even when consumed in large amounts make lactobacilli attractive candidates for live vehicles for the delivery of immunogens to the intestinal mucosa. ( 3) The oral or intranasal administration of Lactobacillus-based vaccines is a promising method to control mucosal infection because these vaccines could induce strong humoral and cellular immune responses both in the blood and at mucosal sites.
    • "One particularly promising subunit vaccine for MAP is the 70 kDa heat shock protein termed Hsp70 (Koets et al., 2006), which activates B cells (Vrieling et al., 2013). Lactobacillus are interesting candidates for the development of novel oral vaccine vectors due to certain strains widespread use in the food industry and GRAS (generally regarded as safe) status (Yu et al., 2013 ). Specific members of this genus are also an attractive alternative to using attenuated pathogens for mucosal delivery strategies because they can survive the upper gastrointestinal tract (GI) and colonize the lower GI tract (Bermudez-Humaran et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants were preserved in synthetic MMP proteins as shown by monoclonal antibody mediated ELISA. Moreover, MMP is a membrane protein in MAP, which is also targeted to the cellular surface of recombinant L. salivarius at levels comparable to MAP. Additionally, we previously engineered MAP3733c (encoding MptD) and show herein that MptD displays the tendency to associate with the cytoplasmic membrane boundary under confocal microscopy and the intracellularly accumulated protein selectively adheres to the MptD-specific bacteriophage fMptD. This work demonstrates there is potential for L. salivarius as a viable antigen delivery vehicle for MAP, which may provide an effective mucosal vaccine against Johne's disease.
    Full-text · Article · Sep 2014
    • "Current commercial vaccine strategies are insufficient in stemming the spread of the pathogen, while experimental vaccines fail to evoke a complete prophylactic effect, instead reducing the clinical severity of the symptoms and limiting faecal shedding ( Santema et al., 2011). The oral administration of Lactobacillus-based vaccines is an intriguing prophylactic approach to dealing with pathogens, such as MAP, which invade via the intestinal mucosa (, 2009 Kajikawa et al., 2012; Yu et al., 2013). Certain Lactobacillus species have been identified as potent oral vaccine carriers for a diverse range pathogenic species including enterotoxigenic Escherichia coli (ETEC), Bacillus anthracis and human immunodeficiency virus type 1 (HIV-1; Wu & Chung, 2007; Mohamadzadeh et al., 2010; Kajikawa et al., 2012). "
    [Show abstract] [Hide abstract] ABSTRACT: Subunit and DNA-based vaccines against Mycobacterium avium ssp. paratuberculosis (MAP) attempt to overcome inherent issues associated with whole-cell formulations. However, these vaccines can be hampered by poor expression of recombinant antigens from a number of disparate hosts. The high G+C content of MAP invariably leads to a codon bias throughout gene expression. To investigate if the codon bias affects recombinant MAP antigen expression, the open reading frame of a MAP-specific antigen MptD (MAP3733c) was codon optimised for expression against a Lactobacillus salivarius host. Of the total 209 codons which constitute MAP3733c, 172 were modified resulting in a reduced G+C content from 61% for the native gene to 32.7% for the modified form. Both genes were placed under the transcriptional control of the PnisA promoter; allowing controlled heterologous expression in L. salivarius. Expression was monitored using fluorescence microscopy and microplate fluorometry via GFP tags translationally fused to the C-termini of the two MptD genes. A > 37-fold increase in expression was observed for the codon-optimised MAP3733synth variant over the native gene. Due to the low cost and improved expression achieved, codon optimisation significantly improves the potential of L. salivarius as an oral vaccine stratagem against Johne's disease.
    Full-text · Article · Apr 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Bacillus subtilis is a vaccine production host and delivery vector with several advantages such as a low production cost, straightforward administration as it is safe for human consumption and the production of spores exerting adjuvant effects. This review summarizes the expression approaches and provides an updated outlook of how a myriad of pathogens have been targeted under this technology. Furthermore, by reviewing the literature, several promising candidates in terms of immunogenic and immunoprotective potential have been identified. The immune profiles achieved comprise either humoral or cellular responses, which reflect versatility for application in the fight of distinct pathologies that demand specific polarization on the immune responses. Some perspectives for this field are also envisioned.
    Full-text · Article · May 2015
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