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Principal Investigator: STEVEN GREGORY REED
Organization: HDT BIO CORPORATION
Fiscal Year: 2022
Award: $550,719
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
Our team - in collaboration with other vaccine developers - has been actively involved in tuberculosis (TB)
vaccine discovery for the past three decades and led the team that developed the M72 vaccine that has provided
proof of concept for effective subunit TB vaccines. Obstacles limiting commercial deployment of M72 include
limited efficacy (~50% prevention of disease) and cost of goods for large-scale production. With these
considerations in mind, our group developed a second-generation subunit vaccine, ID93, which consists of four
protein antigens (M72 has two) formulated with a synthetic TLR4 targeted adjuvant formulation, as opposed to
the natural product-based adjuvant contained in the M72 vaccine. ID93 has progressed to Phase 2 human clinical
trials, with promising results and is currently in further development. Human immune responses measured
against the ID93 components have been instructive and have allowed further antigen prioritization with a goal of
complementing the antigens of M72.
We have concurrently developed a new RNA vaccine platform - now in clinical development as a COVID-19
vaccine which may be approved in India in summer 2021 - and that induced potent cellular immunity and can be
scaled in a cost-effective manner. Using a select panel of antigens, we will apply our RNA technology for inducing
effective systemic and mucosal immune responses in mice and non-human primates. In addition, each of our
RNA based adjuvants, TLR3 and RIG-I agonists, both being effective inducers of both innate and adaptive
immune responses adds an innovative aspect.
In this proposal, our innovation comes from three main areas of emphasis: First is optimization of the RNA
vaccine technology by using new replicons and delivery systems. Second is applying RNA vaccination with
subunit protein/adjuvant boosting, using adjuvants of known efficacy (TLR4 agonists) in comparison with novel
adjuvants that signal through the TLR-3 or RIG-I pathways. Neither of these have been exploited extensively for
infectious disease vaccines - particularly in the area of mucosal immunity. The third area comes from innovation
in manufacturing and supply: We have novel processes for the production of TBRNA that were transferred to
India (Gennova) and Brazil (CIMATEC). Gennova has already produced 1 million doses, with a target of 100
million by year-end, and has completed Phase 1 and 2 clinical trials in India. Similarly, we have acquired large-
scale access to our adjuvant molecules (TLR4, TLR3, RIG-I), all synthetic, thus avoiding the intellectual property
roadblock encountered with M72.
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