(526f) Design of a Combination Nanovaccine to Induce Rapid and Long Term Protective Immunity Against Bacillus Anthracis

Bacillus anthracis, the causative agent of anthrax, is a highly lethal Gram-positive bacteria due to its ability to produce lethal and edema toxins. In addition to its virulence, B. anthracis has the ability to form durable endospores, allowing it to survive in the environment for decades. Because of these attributes, this pathogen has a history of use as a biological warfare agent, as in the events following 9/11, which resulted in the deaths of five civilians and possible exposure to 30,000 others. Currently, there is an FDA-approved vaccine formulation, Anthrax Vaccine Absorbed (AVA), which consists of culture supernatants of predominantly protective antigen (PA), the receptor-binding component for both lethal toxin and edema toxin, adsorbed to aluminum hydroxide. Although efficacious, the vaccine regimen consists of three immunizations within the first six months to achieve protective immunity followed by boosters at 12 and 18 months and yearly boosters afterward. Therefore, there still remains a need for an anthrax vaccine formulation that can provide both rapid and long-lived protective immunity in the event of exposure of warfighters or civilians to B. anthracis, while also improving patient compliance through reducing the number of immunizations required.

Polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) consisting of 1,6-bis(p-carboxyphenoxy) hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) provide a solution to these challenges. These biodegradable compounds are safe, biocompatible, and have demonstrated the ability to maintain the structural stability and functional activity of encapsulated PA over the course of four months. The current study investigated the ability of polyanhydride nanovaccines containing PA and the cyclic dinucleotide, cyclic di-GMP, a known activator of the STING pathway, to elicit rapid and long-lived protective immunity against B. anthracis. In this study, three separate groups of female C57BL/6 mice were immunized with the PA nanovaccine and serum samples were collected and analyzed for antibody titer, avidity, and epitope specificity at specified time points post-immunnization. In addition, a lethal factor neutralization assay was performed to evaluate the functional antibody titer of the immunized mice. Mice were later challenged at 14, 42, or 70 days PI with a lethal dose of Ames strain B. anthracis and survival rates of the vaccinated mice were assessed.