August 12, 2020

professional photo of Scott KenneyNew viruses are like wild animals. They’re hard to contain, unpredictable, and can be deadly if you’re not careful. Even when you do contain a new virus, that doesn’t necessarily stop it from being dangerous—a caged wolf is still a wolf.

Because of this, scientists have to take significant precautions when working with new viruses. The Centers for Disease Control and Prevention (CDC) sets Biological Safety Levels (BSL) for labs based on the potential danger the agent or organism being studied poses to lab personnel as well as the surrounding environment and community. Levels range from the lowest BSL-1 for basic labs studying nonlethal agents that pose minimal risk, such as non-pathogenic E.coli, to the highest BSL-4 for deadly infectious agents that pose a high risk, such as Ebola and Lassa virus. The precautionary restraints and containment measures required for a lab increase with each safety level. A wooden fence might be sufficient for containing a sheep, but not a wolf.

For example, a novel infectious agent like SARS-CoV-2 requires BSL-3 safety precautions. A BSL-3 lab has to take all of the precautions required for BSL-1 and BSL-2 labs plus a number of additional measures. BSL-3 labs often require all lab personnel to undergo medical surveillance, perform all work with infectious material in biosafety cabinets, shower out of the facility, and wear protective garments. BSL-3 lab facilities, themselves, usually require highly-specific features like directional airflow, special sterilizers to decontaminate all waste leaving the facility, and entrances away from areas of the building with unrestricted access.

Because of all these needed precautions, BSL-3 labs are more difficult for scientists to get approval to work in, not to mention how difficult the work is to perform under BSL-3 conditions, and the added expense of doing the work in such a facility. Like anyone performing a complicated job, scientists would rather work in less restrictive conditions—and with less dangerous material. But when you’re trying to develop a vaccine to protect against a dangerous virus, like SARS-CoV-2, you need the real danger to ensure the vaccine really works.

Or, at least, something that looks like real danger. That’s what Dr. Scott Kenney, an assistant professor in the OARDC Food Animal Health Research Program (FAHRP) and in the College of Veterinary Medicine, realized when he started working on a project to address the COVID-19 pandemic. Dr. Kenney has experience working with self-inactivating lentiviruses, a type of retrovirus that is engineered to not continually replicate in mammalian cells.

Lentiviruses are commonly used to create pseudotyped viruses. A pseudotyped virus is a virus particle that can contain proteins from a more dangerous virus, like SARS-CoV-2, on the surface of a much less dangerous viral vector, like a lentivirus. A sheep in wolf’s clothing, if you will.

Therefore, Dr. Kenney decided to develop a pseudotyped lentivirus that looks like SARS-CoV-2 but doesn’t require the same level of safety precautions. Since the pseudotyped lentivirus looks like SARS-CoV-2, though, Dr. Kenney and his team can still use it to test a SARS-CoV-2 vaccine—and that’s exactly what they’re doing.

Dr. Kenney has partnered with Dr. Renukaradhya Gourapura, a professor in both the College of Veterinary Medicine and OARDC’s FAHRP group located on OSU’s Wooster campus, who specializes in nanoparticle vaccine platforms, to test a nanoparticle delivery system of SARS-CoV-2 antigens. Antigens are the molecules often found on the outside of pathogens that trigger the body’s immune response. When the immune system detects antigens from a specific virus, it starts mobilizing antibodies tailored to combat that virus. Sticking with our wolf analogy, it’s as if you heard howling in the distance, you would know you might need to prepare for a wolf.

After the SARS-CoV-2 antigens delivered by Dr. Gourapura’s nanoparticle vaccine candidates convince the immune system to prepare for SARS-CoV-2, Dr. Kenney’s pseudotyped lentivirus can be used to test how well the vaccine prepared the host for them—all in BSL-2 conditions.

IDI spoke to Dr. Kenney more about his partnership with Dr. Gourapura and his idea to use pseudotyped lentiviruses to conduct vaccine testing without being afraid of the big, bad COVID-19.

What initially inspired your project?

As soon as we recognized that COVID-19 was going to be spread globally a number of working groups involving faculty such as Dr. Linda Saif, a distinguished university professor in the College of Veterinary Medicine, Dr. Gene Oltz, chair of the Department of Microbial Infection & Immunity, and many others with significant interests in infectious diseases and affiliated with the Infectious Diseases Institute or the Wexner Medical Center convened. Faculty with existing expertise in virology and assay development were approached and asked if they could fill essential needs such as serological assays to detect COVID-19 infection, potential therapeutics, and vaccine development. From previous knowledge of SARS and MERS experiments it was found that pseudotyped lentiviruses were useful for testing therapeutics and vaccine candidates. Having Food Animal Health Research Program (FAHRP) ties with faculty with years of coronavirus experience such as Drs. Linda Saif, Qiuhong Wang, and Anastasia Vlasova put me in an ideal position to help make some of these needed assays. Existing ties with Dr. Renukaradhya Gourapura in making a vaccine for African swine fever virus using his nanoparticle platform seemed to make an ideal working platform to combine pseudotyped lentivirus with nanoparticle vaccine testing for SARS-CoV-2.   

What is the goal of your project?

The project goals are twofold. First, we are creating a pseudotyped self-inactivating lentivirus that has SARS-CoV-2 spike protein expressed on its membrane. This lentivirus uses both luciferase and green fluorescent protein as readouts. Instead of using SARS-CoV-2 for testing patient serum and animals inoculated with test vaccine candidates needing BSL-3 safety precautions we will be able to screen convalescent patient serum and serum from vaccine candidates in BSL-2 conditions. Our second goal is to apply a novel vaccine platform developed by Dr. Gourapura to use nanoparticles to deliver SARS-CoV-2 antigens. Dr. Gourapura’s nanoparticle vaccine is effective for preventing swine influenza virus and creates a robust mucosal immune response. It can be an ideal second-generation vaccine candidate helping to make a better immune response than current vaccine candidates in the development pipeline. We can combine the nanoparticle vaccine trials with the pseudotyped lentivirus validating both tools.    

Does this project relate to any research or work you were doing before the pandemic? If so, how?

I had existing ties with Dr. Renukaradhya Gourapura as we had achieved Ohio Agricultural Research and Development Center (OARDC) SEEDs funding proposing to make a nanoparticle vaccine for African swine fever virus. He has significant experience with nanoparticles as a vaccine platform having patented vaccines in use for swine influenza virus and porcine reproductive and respiratory syndrome virus. For the pseudotyped lentivirus, I have utilized self-inactivating lentiviruses for gene editing purposes for many years now. Typically, we pseudotype lentivirus utilizing vesicular stomatitis virus glycoprotein (VSV.g). We have modified our lentivirus protocols to replace VSV.g with the SARS-CoV-2 spike protein and altered the transfer vector to express both luciferase and green fluorescent protein.

Have you had to adjust any of your normal research practices to accommodate the stay-at-home order?

Yes, everyone is making significant sacrifices to conform to OSU and government regulations regarding social distancing. All research in my laboratory not relating to COVID-19 was shut down. Only essential employees for COVID-19 are allowed in the lab and have to wear masks when working. When not working directly on essential COVID-19 assays I have spent considerable time teleworking.

Do you expect the findings from your project to have a lasting impact beyond responding to the COVID-19 pandemic?

I really hope the tools that we are creating can be the basis of a rapid response type of system in which we can identify potential pandemic viruses in the environment prior to their jump and spread into humans. We can place epitopes from these viruses into the nanoparticle vaccine platform then quickly validate these vaccines using similar pseudotyped lentiviruses. We can then keep emergency supplies of these vaccines or the tools to quickly make them available if another pandemic occurs. 

Outside of developing research projects, what have you been doing to cope with COVID-19?

I’ve been serving on several committees attempting to address concerns from our agricultural stakeholders regarding impacts from COVID-19. I’ve done several media interviews on coronaviruses. Outside of work it’s basically trying to stay at home as much as possible, wearing a mask when I do go out, and just generally trying to be vigilant and considerate of my fellow humans.

 

Written by Brooke Zentmeyer.

 

Dr. Scott Kenney is an assistant professor at the College of Veterinary Medicine in the Department of Veterinary Preventive Medicine and Food Animal Health Research Program.

Dr. Renukaradhya Gourapura is a professor at the College of Veterinary Medicine in the Department of Veterinary Preventive Medicine and Food Animal Health Research Program.

 

Read more interviews with IDI members who received COVID-19 Seed Grant funding from the Office of Research.

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