A new vaccine in development by researchers at UVA Health and Virginia Tech could offer broad protection against coronaviruses, including existing and future COVID-19 strains, and cost only $1 per dose.
UVA Health’s Steven L. Zeichner, MD, PhD, and Virginia Tech’s Xiang-Jin Meng, MD, PhD, created the vaccine using an innovative approach that Zeichner says might one day open the door to a universal vaccine for coronaviruses, including those that have threatened pandemics or cause some cases of the common cold.
The researchers made the vaccine using a platform Zeichner invented to rapidly develop new vaccines. Along with expediting vaccine creation, “Our platform offers a new route to rapidly produce vaccines at very low cost. These can be manufactured in existing facilities around the world, which should be particularly helpful for pandemic response,” Zeichner says. Additionally, public health experts could easily transport and store the vaccine, even to remote areas.
Both the approach and the resulting vaccine could transform the ability for countries of all sizes and economic strata to contain pandemics. To that end, Zeichner and Meng are in talks with the World Health Organization’s International Vaccine Institute in Seoul, South Korea, which is charged with making vaccines available around the world, particularly in disadvantaged countries or for potentially pandemic diseases.
Testing Success & Next Steps
The vaccine has so far proved promising in animal testing, preventing pigs from becoming ill with a pig-model coronavirus, porcine epidemic diarrhea virus (PEDV). PEDV infects pigs, causing diarrhea, vomiting, and high fever, and has been a large burden on pig farmers around the world. When PEDV first appeared in pig herds in the U.S., it killed almost 10% of U.S. pigs.
“We are continuing to work very hard,” Zeichner said. “Since those early results, we have been systemically testing how we can best administer the vaccine, either orally, intranasally or intramuscularly, and how we can optimize the immune response with different versions of the pieces of the viruses that can get the body to make an effective immune response against the virus.”
“Once we get our process established, we will send materials to the WHO so that they can scale it up and do more advanced trials, hopefully including human trials,” Zeichner said.
New Vaccine Approach
The vaccine Zeichner and Meng are working on is a killed whole-cell vaccine.
Zeichner’s new vaccine-production platform involves synthesizing DNA that directs production of a piece of the virus that can instruct the immune system how to mount a protective immune response against the virus.
That DNA is inserted into a plasmid, which can reproduce within bacteria. The plasmid is introduced into E. coli, instructing it to place pieces of proteins on their surfaces.
One major innovation is that the E. coli have had a large number of genes deleted. Removing many of the bacterial genes, including genes that make up part of its exterior surface or outer membrane, appears to substantially increase the ability of the immune system to recognize and respond to the vaccine antigen placed on the surface of the bacteria.
To produce the vaccine, the bacteria expressing the vaccine antigen are grown in a fermenter, much like the fermenters used in common microbial industrial processes like brewing. They're then killed with a low concentration of formalin.
“Killed whole-cell vaccines are currently in widespread use to protect against deadly diseases like cholera and pertussis. Factories in many low-to-middle-income countries around the world are making hundreds of millions of doses of those vaccines per year now, for a $1 per dose or less,” Zeichner explains. “It may be possible to adapt those factories to make this new vaccine. Since the technology is very similar, the cost should be similar, too.”
The entire process, from identifying a potential vaccine target to producing the gene-deleted bacteria that have the vaccine antigens on their surfaces, can take place very quickly, in only 2 to 3 weeks.
Zeroing in on Regions of the Coronavirus
Currently available COVID-19 vaccines focus on the COVID-19 virus’ entire spike protein. Zeichner and Meng’s vaccine concentrates more closely on two regions of that spike protein: the fusion peptide region and the stalk region. These regions have universal vaccine potential because they:
- Appear in every sequence of the COVID-19 virus identified so far
- Seem to be necessary for the virus to survive
- Show little to no variation across all studied viruses
Zeichner sums it up, saying, “We are trying to make a vaccine against a piece of the virus that cannot mutate. The fusion peptide region, for example, is so invariant that every single coronavirus we know of has the same 6 amino acids in the center of that region — not just in humans, but in animals.”
The Advantage of Studying a Native Host
Meng and Zeichner made two vaccines, one designed to protect against COVID-19, and another designed to protect against PEDV. PEDV and the virus that causes COVID-19 are both coronaviruses. Though distant relatives, they, like all coronaviruses, share several of the amino acids that constitute the fusion peptide.
One advantage of studying PEDV in pigs is that Meng and Zeichner could observe the ability of the vaccines to offer protection against a coronavirus infection in the native host. Other models used to test COVID-19 vaccines study SARS-CoV-2 in non-native hosts, such as monkeys or hamsters, or in mice that have been genetically engineered to enable them to be infected with SARS-CoV-2. Because of their similar physiology and immunology, pigs may be the closest animal models to people outside of primates.
In some unexpected results, Meng and Zeichner observed that both the vaccine against PEDV and the vaccine against SARS-CoV-2 protected the pigs against illness caused by PEDV. The vaccines did not prevent infection, but they protected the pigs from developing severe symptoms, much like the observations made when primates were tested with candidate COVID-19 vaccines. The vaccines also primed the immune system of the pigs to mount a much more vigorous immune response to the infection.
If both the PEDV and the COVID-19 vaccines protect pigs against disease caused by PEDV and prime the immune system to fight disease, it's reasonable to think that the COVID-19 vaccine would also protect people against severe COVID-19 disease, the scientists say.
While additional testing is needed, the collaborators are pleased by the early successes of the vaccine-development platform.
The researchers published their findings in the scientific journal PNAS. The findings are under peer review. The research team consisted of Denicar Lina Nascimento Fabris Maeda, Debin Tian, Hanna Yu, Nakul Dar, Vignesh Rajasekaran, Sarah Meng, Hassan Mahsoub, Harini Sooryanarain, Bo Wang, C. Lynn Heffron, Anna Hassebroek, Tanya LeRoith, Xiang-Jin Meng, and Steven L. Zeichner.
Zeichner is the McClemore Birdsong Professor in the UVA Departments of Pediatrics and Microbiology, Immunology and Cancer Biology, the director of the Pendleton Pediatric Infectious Disease Laboratory, and part of UVA Children’s Child Health Research Center. Meng is University Distinguished Professor and a member of Virginia Tech’s Department of Biomedical Sciences & Pathobiology.