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CEPI Assessing Advanced RNA Nanoparticle Vaccine

Zika virus

Transmission electron microscopic image of Zika virus, a type of flavivirus (CDC.gov)

12 Jan. 2023. An international health organization is evaluating a new type of vaccine made with biodegradable RNA nanoparticles to help head off future viral pandemics. The Coalition for Epidemic Preparedness Innovations, or CEPI, is funding creation and testing of an RNA vaccine by Tiba Biotech LLC in Cambridge, Massachusetts that offers a different RNA vaccine process first developed at MIT.

Early RNA vaccines protecting against viral diseases including Covid-19 use synthetic messenger RNA or mRNA delivered inside nanoscale lipid particles. While the vaccines are largely effective in preventing disease they can also cause adverse side effects, such as soreness from inflammation or fever in some recipients. Most current RNA vaccines also require refrigeration or freezing for storage and delivery, the so-called cold chain, which adds to costs for health authorities and limits their use in lower-resource regions.

As a result, CEPI issued last year a proposal call for advances in RNA vaccines, including “RNA platform technologies based on potentially high-impact innovations offering substantial advantages over existing mRNA technologies.” For developers of these technologies, CEPI offers to support research on discovery and preclinical proof-of-concept studies.

RNA vaccines without the need for lipid nanoparticles

Tiba Biotech was formed in 2018 to commercialize advances in RNA vaccine technology discovered in the lab of bioengineering professor Daniel Anderson at MIT. A team led by Jasdave Chahal, then a postdoctoral researcher in Anderson’s lab, published findings in July 2016 — reported by Science & Enterprise — showing vaccines made with mRNA molecules formulated into nanoscale dendrimer particles. Dendrimers are star-shaped symmetrical molecules with many desirable properties for vaccines, including stability, solubility, and low toxicity. The researchers found they could quickly produce mRNA dendrimer vaccines that produce antibody and T-cell responses protecting lab animals against Ebola, influenza, and other deadly viruses.

Chahal and colleagues went on to found Tiba Biotech and now serves as the company’s chief scientist. Tiba Biotech says its process can design synthetic biodegradable RNA nanoparticles without the need for encasing the RNA in lipids. As a result, says the company, its process can deliver higher doses of RNA for vaccines, as well as cancer treatments and gene therapies. In addition, says Tiba, the larger capacity of its nanoparticles can carry more complex deliveries, such as multiple antigens and Crispr gene editing payloads.

For CEPI, Tiba Biotech is creating a vaccine to protect against Japanese encephalitis virus, a disease caused by a flavivirus, a virus family causing a number of vector-borne diseases resulting in recent epidemics including dengue, West Nile, yellow fever, and Zika. CEPI is providing $2 million to Tiba to design, develop, and test in preclinical studies a vaccine protecting against Japanese encephalitis virus or JEV. The goal of the project is to assess the vaccine’s potential for eventually producing less costly and more efficient vaccines with fewer adverse effects. If successful, say CEPI and Tiba, the project could be extended to develop vaccines against other known viruses, as well as prepare for vaccines against as yet unknown pathogens with pandemic potential.

Richard Hatchett, CEO of CEPI notes in a statement, “mRNA vaccines have been a game changer for the global pandemic response, but there is scope to substantially improve the technology to make it more effective and accessible when responding to future outbreaks.” Christian Mandl, Tiba Bioech co-founder and interim chief scientific officer adds, “This initial focus on JEV is just the start to developing, expanding, and enhancing RNA vaccine rapid-response capabilities against known and unknown threats.”

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