Targeted Expression of Anthrax Protective Antigen by Lactobacillus Gasseri as an Anthrax Vaccine

Abstract

Lactobacillus-based delivery offers tremendous practical advantages. Recombinant antigens such as PA would not require chemical coupling agents, and the recombinant bacteria can be administered orally where upon both mucosal and systemic immune responses are elicited.

Recent progress in the development of anthrax vaccines

“…The construct expressing PA-DCpep elicited serum anti-PA titers, neutralizing PA antibodies, and the levels of IgA-expressing cells at par with the conventional recombinant PA plus aluminum hydroxide vaccine administered subcutaneously [117]. It induced robust protective immunity against B. anthracis Sterne challenge, resulting in complete animal survival [118]. This improved expression vaccine strategy reduced the number of inoculations and length of the boosting period, leading to animal protection via efficacious bacterial adjuvanticity and safe oral delivery of this vaccine to mucosal immune cells, including dendritic cells.…”

Bioengineered probiotics, a strategic approach to control enteric infections

“…87 Likewise, expression of PA in L. gasseri also provided 100% protection against anthrax in a mouse model. 88 Probiotics were also engineered to deliver vaccines to the mucosal surfaces. The first recombinant probiotic oral vaccine was developed by expressing the tetanus toxin fragment C in Lactococcus lactis.…”

Directional Activation of Intestinal Dendritic Cells by Oral Targeted Multivalent Vaccine

“…Although immune tolerance to a commensal inhabitant of the gastrointestinal mucosa was an initial concern with this strategy certain lactobacilli such as L. gasseri, are able to overcome tolerance likely via strong innate adjuvant properties [7,8]. Using L. gasseri, our laboratory has been able to deliver the protective antigen (PA) of Bacillus anthracis to vaccinated mice to resist this potential agent of bioterrorism [2]. Additionally, another group has used L. gasseri for successful delivery of Salmonella antigens [9].…”

“…With the goal to discover a specific DC-targeting peptide moiety, a phage display library was sequentially absorbed with monocytes, T cells, B cells, and Langerhans cells and then screened for the ability to bind human myeloid-derived DCs [11]. The obtained sequence was then tested for its in-vitro binding capacity and its application in antigen delivery in a murine model of oral vaccination by fusing this DC targeting peptide to PA of Bacillus anthracis [1,2,12].…”

“…First, in order to protect the antigen from harsh gastric juices, Lactobacillus species, including L. acidophilus or L. gasseri, bacteria that can survive and thrive in the gastrointestinal tract, were modified to secrete the antigen of interest in the gut. Second, to assist in the delivery of antigen to the professional antigen presenting cells, a twelve amino-acid long tag was added to the immunogenic vaccine subunit [1,2].…”