A vaccine candidate that could provide protection against the COVID-19 virus and other coronaviruses has shown promising results in early animal tests.
Candidate coronavirus vaccines, created by distinguished professor XJ Meng of Virginia Tech University and professor Steven L. Zeichner of UVA Health, have prevented pigs from getting sick with swine coronavirus, the epidemic diarrhea virus porcine (PEDV).
The researchers recently published their findings in the Proceedings of the National Academy of Sciences.
“The vaccine candidate was developed using an innovative vaccine platform targeting a highly conserved genomic region of coronaviruses,” said Meng, professor emeritus in the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland College of Veterinary Medicine. “The new vaccine platform uses a small-genome bacteria to express the coronavirus vaccine antigen on its surface. Such a vaccine platform can be manufactured at low cost in existing facilities around the world, which could meet pandemic demand. “
Their coronavirus vaccine offers several benefits that could overcome major obstacles to global vaccination efforts. It would be easy to store and transport, even to remote parts of the world, and could be produced in large quantities in existing vaccine factories.
“Our new platform offers a new avenue to rapidly produce very low cost vaccines that can be manufactured in existing facilities around the world, which should be particularly useful for the response to a pandemic,” said Zeichner.
A new approach to vaccine development
The new vaccine production platform involves synthesizing DNA that directs the production of a piece of the virus that can tell the immune system how to mount a protective immune response against a virus.
This DNA is inserted into another small circle of DNA called a plasmid which can reproduce in bacteria. The plasmid is then introduced into the bacteria, causing the bacteria to place pieces of protein on their surfaces. The technique uses common bacteria E. coli.
A major innovation is that the E. coli have had many of his genes deleted. Eliminating many of the bacteria’s genes, including genes that make up part of its outer surface or outer membrane, appears to dramatically increase the ability of the immune system to recognize and respond to vaccine antigen placed on the surface. bacteria. To produce the vaccine, bacteria expressing the vaccine antigen are simply grown in a fermenter, much like fermenters used in common microbial industrial processes like brewing, and then killed with a low concentration of formalin.
“Killed whole cell vaccines are now widely used to protect against deadly diseases like cholera and pertussis.” Factories in many low- and middle-income countries around the world currently manufacture hundreds of millions of doses of these vaccines per year, for a dollar per dose or less, ”said Zeichner. “It may be possible to adapt these factories to make this new vaccine. Since the technology is very similar, so should the cost.”
The whole process, from identifying a potential vaccine target to producing the bacteria deleted from the gene that have the vaccine antigens on their surface, can take place very quickly, in just two to three weeks, making makes the perfect platform to respond to a pandemic.
The team’s candidate vaccines take an unusual approach in that they target part of the virus’s spike protein, the “viral fusion peptide,” which is highly universal among coronaviruses. The fusion peptide has not been observed to differ at all in the many genetic sequences of SARS-CoV-2, the virus responsible for COVID-19, which has been obtained from thousands of patients worldwide over the course of the pandemic.
“With the emergence of various variants of SARS-CoV-2, a vaccine targeting a conserved region of all coronaviruses, such as the fusion peptide, can potentially lead to a widely protective vaccine candidate. Such a vaccine, if successful, would be of significant value against variant viral strains, ”said Meng, who is also the founding director of the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens at the Fralin Life Sciences Institute. by Virginia Tech.
To create their vaccine, the researchers used the new vaccine platform, synthesizing DNA with instructions to make the fusion peptide and bacteria modified to place proteins on the surface of bacteria that had many of its characteristics. genes removed, then grew and inactivated the bacteria to make the candidate coronavirus vaccine.
Meng and Zeichner have made two vaccines, one designed to protect against COVID-19 and the other designed to protect against the swine coronavirus, PEDV. PEDV and SARS-CoV-2, the virus that causes COVID-19, are both coronaviruses, but they are distant relatives. PEDV and SARS-CoV-2, like all coronaviruses, share a number of basic amino acids that make up the fusion peptide. PEDV infects pigs, causing diarrhea, vomiting and high fever and places a heavy burden on pig farmers around the world. When PEDV first appeared in pig herds in the United States in 2013, it killed millions of pigs in the United States alone.
One of the benefits of studying PEDV in pigs is that researchers could study the ability of vaccines to provide protection against coronavirus infection in its native host – in this case, pigs. Other models that have been used to test COVID-19 vaccines are studying SARS-CoV-2 in non-native hosts, such as monkeys or hamsters, or in mice that have been genetically engineered to allow them to be infected with SARS-CoV-2. Pigs are also very similar in physiology and immunology to humans – they may be the closest animal models to people other than primates.
In some unexpected results, Meng and Zeichner observed that the candidate vaccine against PEDV and the candidate vaccine against SARS-CoV-2 protected pigs against disease caused by PEDV. The vaccines did not prevent infection, but they did protect the pigs from developing serious symptoms, much like the observations made when the primates were tested with candidate COVID-19 vaccines. The vaccines also caused the pig’s immune system to develop a much more vigorous immune response to the infection. If the PEDV and COVID-19 vaccines protected pigs against disease caused by PEDV and prompted the immune system to fight the disease, it is reasonable to believe that the COVID-19 vaccine would also protect people against COVID-19 disease. severe.
Additional testing – including human trials – would be needed before the COVID-19 vaccine can be approved by the Federal Food and Drug Administration or other regulatory agencies around the world for use in humans, but employees are satisfied with the initial successes of the vaccine development platform.
“Although the initial results from the animal study are promising, more work is needed to refine both the vaccination platform using different bacterial strains with reduced genome and the target of the fusion peptide vaccine,” said Meng. “It will also be important to test the peptide fusion vaccine in a monkey model against SARS-CoV-2 infection.”
Zeichner added that he was encouraged that a collaboration between UVA and Virginia Tech, schools with a well-known athletic rivalry, had produced such promising results.
“If scientists at AVU and Virginia Tech can work together to try and do something positive to combat the pandemic, then perhaps there is hope for collaboration and cooperation in the country in general, ”Zeichner said.
Virginia Tech and UVA research team
The research team consisted of Denicar Lina Nascimento Fabris Maeda, Hanna Yu, Nakul Dar, Vignesh Rajasekaran, Sarah Meng and Steven L. Zeichner of UVA Health; and Debin Tian, Hassan Mahsoub, Harini Sooryanarain, Bo Wang, C. Lynn Heffron, Anna Hassebroek, Tanya LeRoith, and Xiang-Jin Meng of the Virginia-Maryland College of Veterinary Medicine at Virginia Tech.
Zeichner is Professor McClemore Birdsong in the Departments of Pediatrics and Microbiology, Immunology and Cancer Biology; the director of the Pendleton Pediatric Infectious Diseases Laboratory; and part of the UVA Child and Child Health Research Center. Meng is a University Professor Emeritus and Director of the Virginia Tech Center for Emerging, Zoonotic, and Arthropod -borne Pathogens and a member of the Department of Biomedical Sciences and Pathobiology at Virginia Tech.
Their vaccine development work has been supported by the Pendleton Pediatric Infectious Disease Laboratory, the McClemore Birdsong Chair, and support from the University of Virginia Manning Fund for COVID-19 Research and the Ivy Foundation. The work was also partially funded by the Virginia-Maryland College of Veterinary Medicine and internal funds from Virginia Tech.