Progress and challenges associated with the development of ricin toxin subunit vaccines

ABSTRACT

The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine, including the completion of two Phase I clinical trials with two different recombinant A subunit (RTA)-based vaccines: RiVax™ and RVEc™ adsorbed to aluminum salt adjuvant, as well as a non-human primate study demonstrating that parenteral immunization with RiVax elicits a serum antibody response that was sufficient to protect against a lethal dose aerosolized ricin exposure. One of the major obstacles moving forward is assessing vaccine efficacy in humans, when neither ricin-specific serum IgG endpoint titers nor toxin-neutralizing antibody levels are accepted as definitive predictors of protective immunity. In this review we summarize ongoing efforts to leverage recent advances in our understanding of RTA-antibody interactions at the structural level to develop novel assays to predict vaccine efficacy in humans.

KEYWORDS:

• Toxin
• biodefense
• vaccine
• protection
• antibody
• neutralizing
• epitope

Acknowledgements

We thank Dr. Michael Rudolph at the New York Structural Biology Center, and Drs. Ronald Toth IV, David Weis, David Volkin at the University of Kansas allowing us to cite unpublished results in this review. We thank Greta Van Slyke, Yinghui Rong, and Jennifer Westfall at the Wadsworth Center for thoughtful discussions.

Declaration of interests

This work was supported in part by Contract No. HHSN272201400021C from the National Institutes of Allergy and Infectious Diseases. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.