As COVID-19 continues to spread throughout the country and the world, EpiVax, a biotechnology company based in Providence, is currently leading collaborative efforts to design a vaccine against the virus.

EpiVax has been dedicated to applying (their) tools to re-engineering therapeutic proteins and to designing new vaccines, according to their website. They are partnering with researchers from four organizations to work on the COVID-19 vaccine: Generex Biotechnology, the University of Georgia, Immunomic Therapeutics and an organization based in Belgium. Other researchers have reached out to the company to aid in collaborative efforts as well.

Bringing Potential Benefits

The candidate vaccines being developed by EpiVax are T-cell-based. Unlike other COVID-19 vaccines in the works that are B-cell-based, the T-cell vaccines do not stimulate antibodies, which are molecules created by the immune system to protect against infection. Some studies have proposed that in the case of COVID-19, antibody stimulation may exacerbate respiratory symptoms, said Katie Porter, EpiVaxs business development manager.

From studies on other coronaviruses, we have learned that often the antibodies are not long-lived, so they do not hold up their defense against invading viruses for extended periods of time as the virus evolves, said Lalit Beura, assistant professor of molecular microbiology and immunology, whose research involves T-cells. Having another arm of the immune system in the form of a T-cell-focused vaccine is helpful.

EpiVax: Starting with Sequencing

There are people who are concerned that were working with the actual virus in Providence, but that is not the case, Porter said. Rather, EpiVax is using a digital representation. After determining the viruss genome, the researchers selected the amino acid sequences that form the COVID-19 SARS-CoV-2 proteins that T-cells recognize and used a computer-based technology they developed to determine the regions of these proteins that instigate the greatest immune system response. The researchers will use these short protein segments to design vaccine candidates.

EpiVax has created three designs for the collaborators to use for their distinct, biological methods of delivering the vaccine. These designs include a set of distinct, short peptides, a string of connected peptides and a modified protein. Peptides are composed of the same molecules as proteins but are shorter. We are working with various collaborators on a daily basis to provide them with the best design options for their platform technology, Porter said. For instance, the Generex collaborators are using a set of peptides while the University of Georgia collaborators will be using the modified protein model consisting of the full viral protein.

While each of these organizations is working on their own projects, they all share a common goal of developing a vaccine. EpiVax has begun delivering its protein designs to its collaborators and optimizing the strains for their mechanism. For the company, sharing their sequencing and initial design work with collaborators who can help create an eventual vaccine is important because we have the ink, and we need to give it to someone with the pen so that together we can write, Porter said.

University of Georgia: Modifying the Protein Model

Ted Ross, director of the Center for Vaccines and Immunology, Georgia Research Alliance Eminent Scholar and professor of infectious diseases at the University of Georgia, and two other investigators at the university will engineer the modified protein sequences that EpiVax is designing. Then they will run trials in animal models mice and ferrets by infecting them with the altered peptides to determine whether they produce a better immune response than the wild type viruss proteins do. If this is the case, the researchers plan to expose these animals to SARS-CoV-2 to ensure that this potential vaccination is effective. The groups expectation is to have this data ready by the middle of this summer.

Ross and his group have also been working on developing a universal flu vaccine, a vaccine that could potentially be used for all influenza viruses without requiring constant changes. Perhaps we could use those (same) techniques to eventually create a universal coronavirus vaccine, Ross said.

Generex Biotechnology: Modifying the Peptide Model

Generex Biotechnology, another therapeutics company, is modifying the peptides provided by EpiVax. They are first synthesizing the peptides predicted by EpiVaxs analysis using their Ii-Key technology. An li-Key facilitates the attachment of a four-amino-acid-long peptide to a part of the COVID-19 virus. This technology serves as a sort of flag on the virus, providing a way to artificially activate the T-cells more quickly than would happen in a typical immune response.

The researchers plan on conducting their studies by testing the modified peptides, determined by EpiVax and optimized by Generex, using blood cells from COVID-19-recovered patients. They hope to complete these studies in three to four months prior to testing the potential vaccine in live animals and people.

It is a two-fold process, said Eric von Hofe, chief scientific officer of NuGenerex Immuno-Oncology, a subsidiary of Generex. The team will be looking for a T-cell response to these peptides, as well as the generation of antibodies. After starting and completing trials in animal models, Generex hopes to begin clinical trials with about 200 volunteers that will receive the peptide-based vaccine to determine whether this produces the desired immune response and to ensure the safety of the vaccine.

The biggest advantage is that peptides represent the minimal unit required to produce an immune response while reducing safety concerns associated with other proposed COVID-19 vaccines that are RNA- and DNA-based and have the potential to insert into a persons DNA, von Hofe said. But none of these types of vaccines have been approved yet for the treatment of infectious diseases, he added.

Fundamentals of Funding

Despite the preliminary successes the companies have seen thus far, funding remains a critical part of the picture. Funding often pushes back the timeline, or worse, cancels hopes of a trial continuing. EpiVaxs and Generexs earlier research on vaccine candidates for the H1N1 and SARS pandemics were halted largely due to funding limitations.

Still, the companies believe that this time around, it will not be as much of a barrier. If our trials are successful, Im sure that there will be opportunities to take a vaccine candidate even further, Porter said. There is government and other funding available, but there are many people trying to get it. We have many collaborations in place to move a COVID vaccine forward, so chances for success are very good.

Von Hofe highlighted the importance of reaching out to government officials, as well as voting for political candidates who will support vaccine research. Public interest is acute in the midst of a pandemic and then fades away, von Hofe said. But with the last 20 years having brought a handful of pandemics, now it is pretty clear that the regular emergence of pandemic or potentially pandemic viruses will not be going away, he added. Whatever happens with COVID-19, we will have learned a lot that will be applicable to whatever potential pandemic may come next; it is clear that we need to be better prepared.

While the timeline for this COVID-19 vaccines development remains indefinite, according to EpiVaxs website, were in the race to have the vaccines in clinical trials by the fall, Porter said.

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Providence-based EpiVax collaborates on ongoing research for a COVID-19 vaccine - The Brown Daily Herald