- Self-amplifying RNA vaccine, delivered by cationic nanocarrier (LION™) elicits neutralizing antibody responses in mice and nonhuman primates and protects mice from enterovirus D68 (EV-D68) respiratory infection and resulting disease in mice.
- Findings published in the peer-reviewed journal Science Translational Medicine
SEATTLE, Aug. 7, 2024 -- HDT Bio Corp., a developer of immunotherapies for oncology and infectious diseases, today announced the publication demonstrating the potential for self-amplifying RNA vaccines to be used as tools in our pandemic preparedness toolbox against non-enveloped viruses, a unique group of pathogens.
RNA vaccines have revolutionized our ability to respond to pandemics in a timely manner, however, to date, a roadmap for such a response has only been developed and executed for certain enveloped viruses, "a relatively easy target for the technology", says Dr. Jesse Erasmus, Director of Virology at HDT Bio and senior author. "Both enveloped viruses and RNA vaccines share at least one thing in common; each convert their host cells into bioreactors. In contrast, non-enveloped virusesdepend on complex processes to release their progeny from infected cells, and co-opting those mechanisms to release vaccine antigens from RNA messages is less straightforward."
Non-enveloped viruses, belonging to the same family of viruses that cause Polio, were recently identified as having pandemic potential by the National Institutes of Allergy and Infectious Disease (NIAID). To date, no mRNA vaccines have been described for this group. To develop a roadmap, the authors focused on a prototype member, enterovirus D68 (EV-D68), which spreads via the respiratory route and is implicated in a neuroinvasive disease of children, called acute flaccid myelitis.
The study, funded by National Institutes of Health (NIH) and led by researchers at HDT Bio in collaboration with the Rocky Mountain Laboratories (NIAID/NIH), The Institute for Quantitative Biomedicine at Rutgers, and University of Chapel Hill School of Medicine, investigated the efficacy of HDT Bio's self-amplifying repRNA/LION™ technology for vaccination against EV-D68 respiratory infection and resulting disease. The researchers characterized the antigenic landscape of EV-D68 variants to inform vaccine composition requirements related to circulating strains. Additionally, they demonstrated robust neutralizing antibody responses after vaccination.
Given the poor ability of current mRNA vaccines to protect the upper respiratory tract and therefore reduce transmission of the respiratory virus that causes COVID-19, the authors also evaluated whether HDT's platform could offer any improvements compared to conventional lipid nanoparticle technology in mouse models of EV-D68 respiratory infection. In this model, the RNA vaccine was similar to COVID-19 vaccines, which provided great protection of the lower respiratory tract but poor control of virus in the nose. In contrast, HDT's vaccine formulated with LION™ was able to control virus in both the nose and the lungs, despite being delivered into the muscle. "Mucosal vaccination by spraying vaccine in the nose or delivery to other mucosal surfaces, is thought to be required for protection of those surfaces", said Dr. Nikki Warner, first author, "so this is a significant finding, especially if replicated in larger animal models or in humans". Previously, HDT published studies demonstrating robust control of the virus that causes COVID-19 in the noses of LION™/repRNA-vaccinated hamsters and nonhuman primates.
The publication can be found on the Science Translational Medicine website and on the Publications page of the HDT Bio website.
More information, including a copy of the paper, can be found online at the Science Translational Medicine press package at https://www.eurekalert.org/press/medpak/.
About HDT Bio
HDT Bio is a Seattle-based, clinical-stage biopharmaceutical development company. With core technology and expertise in nucleic acid formulation, the company develops products that seek to harness host-directed immune responses. HDT Bio's work focuses on infectious disease and oncology vaccines and therapeutics through early-stage collaborations with partners worldwide. The company's vaccine platforms combine formulation and adjuvant ingredients to stabilize and deliver RNA to the immune system to stimulate responses. HDT Bio's repRNA/LION™ was the first self-amplifying RNA vaccine platform to ever receive a regulatory authorization.
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