A Novel Antitoxin and Vaccine Platform Based on Nodavirus VLPS

Inventors: John Young, Anette Schneemann, Marianne Manchester, Kelly Dryden, John Harlett, Darly Manayani, Godfrey Rainey, Vilay Reddy, Marc Saladi, Heather Scobie, Diane Thomas, Mark Yeager
Potential Uses: Infection, Vaccine, Drug Discovery and Development
A novel, chimeric virus-like particle (VLP) capable of multivalent display of PA shows significant advantages over existing monovalent PA immunogens for anthrax toxin. Studies indicate VLP-PA complex may eliminate the need for lengthy immunization schedules by providing immunity after a single injection, and has potential to generate effective vaccines against other pathogens, including combination vaccines immunizing against multiple toxins.

The recent use of Bacillus anthracis as a bioweapon has stimulated the search for novel anthrax antitoxins and vaccines that act rapidly with minimal adverse effects. B. anthracis produces a toxin composed of the receptor-binding moiety protective antigen (PA) and the enzymatic moieties edema factor and lethal factor. Current anthrax-vaccine strategies are based on targeting PA as the critical immunogen; however, these vaccines are molecularly ill-defined, can cause adverse reactions, and are administered in a lengthy immunization schedule (6 doses over 18 months). The development of a well-characterized vaccine that induces rapid immunity after a single injection remains an important goal.

We have developed a novel, chimeric virus-like particle (VLP) capable of multivalent display of PA. In animal studies, rats (5/group) were immunized once with VLP-PA complex, PA alone, or VLP alone as a control. After four weeks the animals were challenged with anthrax lethal toxin. All rats that were immunized with the VLP-PA complex survived, whereas all other animals died. These results illustrate that this recombinant VLP platform, capable of multivalent display of PA, yields a significant advantage over monovalent, soluble PA as an immunogen for anthrax toxin, and represents a novel and highly effective reagent for protection against anthrax.

An additional advantage of this VLP platform is its potential to be used to generate effective vaccines against pathogens other than anthrax, through the use of fusion protein technology to display other immunogens on the VLP. These pathogens include category A, B, and C agents, some of which represent major bioterrorism threats, such as ricin and botulinum neurotoxins. Further, by taking advantage of the multivalent display capability of the VLPs, it is possible that this approach could be used to generate combination vaccines, which could simultaneously immunize against anthrax, ricin, and botulinum toxins while circumventing the need for multiple dosings of immunogens.