New information on ricin immunity released

Soligenix, Inc., has described the systematic identification of neutralizing and non-neutralizing B-cell epitopes on ricin toxin's enzymatic A subunit in a new article published in the online journal Vaccine.

The major findings in the study include the identification of six immunodominant linear B cell epitopes on ricin's enzymatic A subunit, or RTA, and the production of monoclonal antibodies against five of the six immunodominant regions. The study also identified several neutralizing "hot spots" on RTA in specific folding domains and demonstrated that non-neutralizing monoclonal antibodies are directed at a specific folding domain.

"We are providing further detail of the immunological structure of RTA in order to define additional correlates of protective immunity," Robert N. Brey, chief scientific officer of Soligenix and a co-author of the study, said. "Such correlates are important in understanding immune responses from human studies and how they relate to protective immunity in animals when vaccines cannot be directly tested for efficacy."

The study also found a convergence of immunodominant epitopes recognized by several animal species. This recognition was found to be similar between mice and rabbits, which suggests that different species, including humans, may develop a similar immune response to RTA.

The RTA "hot spots," the study says, are responsible for eliciting neutralizing antibodies associated with protective immunity to ricin toxin. There are different, distinct regions of RTA responsible for eliciting protective immunity, the study found.

"Efforts to develop an effective vaccine against ricin toxin are focused on the engineering of attenuated and stable recombinant forms of the toxin's RTA," Dr. Nicholas Mantis, a research scientist at the Division of Infectious Disease, Wadsworth Center, New York State Department of Health, and senior author of the study, said. "These data offer insights into the immunodominant and structural determinants on RTA that give rise to protective immunity, and for the first time provide an immunological rationale for ricin vaccine design."