CONCORD, Calif.—As part of a consortium of research institutes, Cerus Corp. announced it received funding from the U.S. National Institute of Allergy and Infectious Diseases (NIAID) to conduct research into prophylactic vaccines against the bacterial infections that lead to tularemia. Cerus will receive $2.8 million, from a total three-year package of $23 million, to apply its killed-but-metabolically-active (KBMA) technology to develop vaccines that potentially offer the benefits of the more traditional killed and attenuated live vaccines without the concomitant risks.
The other members of the consortium are the Lovelace Respiratory Research Institute and University of New Mexico, both in Albuquerque, Arizona State University, and the University of Texas, San Antonio. It will be led by Dr. Rick Lyons, Director of the Center for Infectious Diseases and Immunity at the UNM Health Science Center.
"Based on the initial success of the anthrax collaboration, Dr. Lyons invited Cerus to expand our innovative approach and become a member of the tularemia vaccine development t eam," says Dr. Thomas Dubensky, Cerus VP of research.
The program includes development of appropriate animal models for testing vaccine efficacy and development of immune correlates and surrogates of protection, and will evaluate numerous vaccine strategies. According to Dubensky, scientific and proprietary information, strains and assays will be shared within the consortium. For example, scientists at UTSA will genetic modify Francisella tularensis strains, which Cerus will characterize and develop as KBMA vaccine candidates. It will then send the candidates to UNM and LRRI for protection studies against challenge with a fully virulent strain in small animals and non-human primates.
"The funds for this research will be important in developing strategies that are not only applicable to a vaccine for [tularemia] but will also assist in defining a paradigm for developing vaccines against other emerging infections," says Lyons. "Emerging infections are recognized as a significant medical issue and innovative approaches to vaccine development are required."
The development of new vaccines is challenged by the double-edged sword of efficacy versus safety. Vaccines generated from recombinant proteins or killed pathogens are generally safe, but trigger a weak immune response, while attenuated pathogens offer effective immune responses but raise concerns about safety.
To create KBMA vaccines, Cerus researchers mutated the microbes to prevent them from replicating, but otherwise left the organism's metabolic machinery intact, allowing it to process normally in vitro and in vivo. In work described recently in Nature Medicine, using Listeria as a model, they were able to trigger a significant immune response in mice and showed that the microbe behaved as expected and were unable to reproduce.
"A broad range of diseases can be addressed by programming these bacteria to express specific antigens, resulting in the induction of targeted immune responses," Dubensky says. "Alternatively, KBMA vaccines can be applied to bacterial diseases based on a modified form of the pathogen itself. This latter case is theoretically advantageous in instances where the antigenic correlates of immune protection are unknown or poorly defined, such as for Mycobacterium tuberculosis. This is the approach we are taking to develop vaccines against anthrax and tularemia."
