LONGITUDINAL STUDY OF IMMUNE RESPONSES TO Q-VAX IN YOUNG HEALTHY ADULTS TO SUPPORT THE DEVELOPMENT OF NOVEL VACCINES FOR Q FEVER AND TESTS FOR EXPOSURE SURVEILLANCE
Abstract
FDA review of new vaccines when human efficacy studies are not ethical and field trials are not feasible, as for Q fever, proceeds under the Animal Rule regulatory pathway. The FDA Animal Rule Guidance recommends “bridging animal responses to humans by careful selection of appropriate immune markers” of vaccine response that “can then be used to establish vaccination dose and schedule in humans” for induction of responses associated with disease prevention. Relevant for development of a Q fever vaccine, the Guidance further recommends “for certain intracellular pathogens, animal models should be selected that demonstrate the induction of a protective antibody response as well as novel cellular immune response markers similar to humans” (italics added). To this end, under contract HDTRA1-15-C-0020 we have used mass cytometry to characterize vaccine responses in murine vaccine/challenge models of Q fever and to examine long-lived memory responses in human Q fever convalescents. Here we propose to bridge the results of these studies by characterizing early post-vaccination immune responses in humans receiving Q-VAX. The results will inform selection of a panel of immune markers that can be observed in humans and associated with protective efficacy in an animal model, which can then be used to guide marker selection for development of novel Q fever vaccines.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 04, 2021
- Source ID
- HDTRA12010006
Entities
People
- Mark Poznansky
Organizations
- Defense Threat Reduction Agency
- Massachusetts General Hospital