June 1, 2020 | Coronavirus vaccine development underway by Vault Pharma

Bioparticle-based delivery system offers potential as a coronavirus therapy

by Wayne Lewis

An emerging company developing biotechnology invented at UCLA is adapting their approach to address the novel coronavirus, with the goal of adding to the anti-COVID-19 arsenal that follows an initial vaccine. The company, Vault Pharma, is working with UCLA and other universities to advance a vaccine with the potential to treat the virus in addition to protecting against it.

Vault Pharma was co-founded by Leonard H. Rome, distinguished professor of biological chemistry and associate director of the California NanoSystems Institute at UCLA, and is headquartered on campus at CNSI’s Magnify incubator. The business’s activities are an example of how technologies that begin in academic labs are moved toward the market, where they can help the most people.    

The Magnify incubator helps to advance nanoscience and -technology based startups by offering entrepreneurs laboratory and co-working space, as well as access to specialized UCLA research facilities — exactly what Vault Pharma needed.

“We are a UCLA company,” said Oliver Foellmer, Vault Pharma’s chief executive officer. “Magnify has been our first real home and a terrific place for us to grow. CNSI is just a dream come true because it connects us with UCLA collaborators and resources, it has a big footprint due to the unique, multidisciplinary nature of the institute and it has commercial space — you couldn’t ask for a better combination in an incubator.”

Vault Pharma creates genetically modified versions of vaults — naturally occurring nanoparticles found inside every human cell. Measured in billionths of a meter, vaults were first discovered in the Rome Lab. While their innate function is not fully understood, Rome suspects vaults play a role in the immune system.

The barrel-shaped nanoparticles comprise a shell made of 78 copies of one particular protein, housing two additional proteins and some genetic material. Rome’s team has re-engineered the vault as a delivery device, loading the interior with proteins for applications such as potential therapies or vaccines.

Already under development are vault-based therapies for diseases such as lung cancer and human papillomavirus. Now, Vault Pharma and its collaborators are modifying the technology to vaccinate against the coronavirus.

Studies suggest that a vault-based vaccine could additionally work as a therapy. While the platform hasn’t been tested in humans, proof-of-concept research indicates that vaults are non-inflammatory but are readily internalized by multiple immune cells, involved with both types of adaptive immunity —bodily defenses that respond to specific invaders.

As with typical vaccines, the vault-based strategy is meant to prevent infection by activating the humoral immune system, which uses antibodies to neutralize foreign microbes in bodily fluids and tag them for elimination by immune cells.

“A vaccine packaged in vaults is also taken up by antigen-presenting cells involved in triggering a cellular immune response, which actively fights disease by attacking and killing infected cells,” Rome said. “In addition, cellular immune responses can impart lasting memory allowing resistance to later virus exposure.”

In this way, a vault-based vaccine might provoke a complete and balanced immune response.

Vault Pharma is designing their vaccine with the Rome Lab and the research teams led by Dr. Otto Yang, a professor of medicine in the division of infectious diseases at the David Geffen School of Medicine at UCLA, and Jeff F. Miller, UCLA’s Fred Kavli Professor of NanoSystems Sciences and the director of CNSI.

“Our collaboration with Vault Pharma is exciting on numerous fronts,” Miller said. “It makes for compelling science, holds significant promise to save lives and delivers on part of CNSI’s mission, to translate discoveries into knowledge-driven commercial enterprises.”

Candidate vaccines will be tested by Northern Arizona University’s Todd French, assistant professor of biological sciences, who is developing animal models for studying coronavirus in NAU’s COVID-19 Testing Service Center. French is an expert in the mechanisms that make infectious microbes more dangerous.

Plans for manufacturing are in progress as well. Working with Mark Arbing, who directs the Fermentation Core Facility in the UCLA Molecular Biology Institute, the company and researchers have developed a method for prompting engineered yeast to produce custom-designed vaults. For potential clinical trials, production of vaccine-laden vaults will be scaled up at the University of Nebraska–Lincoln Biological Process Development Facility, which manufactures engineered proteins and peptides, for research and clinical trials.

Foellmer and Rome caution that their approach is not a frontline defense. A vault-based coronavirus vaccine is intended to add to the armament against the disease after an initial vaccine has been developed and distributed, and could represent a step toward blocking a similar virus outbreak in the future.