New COVID-19 Vaccine May Offer Broad Protection Against Existing and Future Coronavirus Strains at a Cost of $1

Steven L. Zeichner, MD, PhD, of UVA Children’s, says the vaccine can be produced very quickly and at a very low cost in existing factories around the world. The vaccine was developed using a platform invented by Zeichner to speed up vaccine development. Credit: Dan Addison | UVA communication

A COVID-19 vaccine that could protect against existing and future strains of the COVID-19 coronavirus and other coronaviruses, costing approximately $ 1 per dose, has shown promising results in early animal studies.

Vaccines made by Steven L. Zeichner, MD, PhD, of UVA Health and Xiang-Jin Meng, MD, PhD of Virginia Tech, prevented pigs from becoming ill with a porcine model coronavirus, porcine epidemic diarrhea virus (PEDV). The vaccine was developed using an innovative approach that Zeichner says could one day open the door for a universal vaccine against coronaviruses, including coronaviruses that previously threatened pandemics or perhaps even coronaviruses that cause some cases of the common cold.

Their coronavirus vaccine offers several benefits that could overcome major obstacles to global vaccination efforts. It could be easily stored and transported, even in remote areas of the world, and could be produced in large quantities using existing vaccine manufacturing plants.

The scientists at UVA and Virginia Tech created the vaccine using a new platform that Zeichner invented to quickly develop new vaccines. The success of the tests thus bodes well for both the COVID-19 vaccine and Zeichner’s vaccine development approach.

“Our new platform provides a new way to rapidly produce vaccines at very low cost that can be manufactured in existing facilities around the world, which should be especially useful for pandemic response,” said Zeichner.

New vaccine approach

Zeichner’s new vaccine production platform involves synthesizing DNA that directs the production of a slice of the virus that can instruct the immune system how to set up a protective immune response against the virus.

That DNA is inserted into another small circle of DNA called a plasmid that can reproduce in bacteria. The plasmid is then introduced into bacteria, instructing the bacteria to place pieces of protein on their surface. The technique uses the common bacterium E. coli.

An important innovation is that E. coli has deleted many of its genes. Removing many of the bacteria’s genes, including genes that make up the outer surface or membrane, seems to significantly increase the immune system’s ability to increase and respond to the vaccine antigen placed on the surface of the bacterium.

To produce the vaccine, the bacteria that express the vaccine antigen are simply grown in a fermenter, just like the fermenters used in common microbial industrial processes such as brewing, and then killed with a low concentration of formalin.

Xiang-Jin Meng, MD, PhD of Virginia Tech, is co-creator of the new vaccine, which has shown promising results in early testing. Credit: Virginia Tech

“Killed whole-cell vaccines are currently in widespread use to protect against deadly diseases such as cholera and whooping cough. Factories in many low- to middle-income countries around the world now make hundreds of millions of doses of those vaccines a year, at $ 1 per dose or less, ”said Zeichner. “It may be possible to adapt those factories to make this new vaccine. Since the technology is very similar, the costs should also be comparable. “

The entire process from identifying a potential vaccine target to producing the gene-deleted bacteria that have the vaccine antigens on their surface can be done very quickly, in as little as two to three weeks, making the platform ideal for responding to a pandemic.

Targeting Coronavirus

The Zeichner and Meng vaccine takes an unusual approach in that it targets part of the virus’ spike protein, the “viral fusion peptide,” which is essentially universal among coronaviruses. The fusion peptide has not been observed to differ entirely in the many genetic sequences of SARS-CoV-2, the virus that causes COVID-19, obtained during the pandemic from thousands of patients around the world.

Meng and Zeichner have created 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, but they are distant relatives. PEDV and SARS-CoV-2, like all coronaviruses, share different amino acids that make up the fusion peptide. PEDV infects pigs, causes diarrhea, vomiting and high fever, and is a major burden on pig farmers around the world. When PEDV first appeared in pig herds in the US, it killed nearly 10% of US pigs – a swine pandemic.

An advantage of studying PEDV in pigs is that Meng and Zeichner can study the vaccines’ ability to protect against coronavirus infection in the original host, in this case pigs. The other models used to test COVID-19 vaccines study SARS-CoV-2 in non-native hosts, such as monkeys or hamsters, or in mice 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 humans other than primates.

In some unexpected results, Meng and Zeichner noted that both the PEDV vaccine and the SARS-CoV-2 vaccine protected the pigs from disease caused by PEDV. The vaccines could not prevent infection, but they protected the pigs from developing severe symptoms, as did the observations made when primates were tested with candidate COVID-19 vaccines. The vaccines also stimulated the pigs’ immune systems to build a much more potent immune response to the infection. If both the PEDV and COVID-19 vaccines protected the pigs from disease caused by PEDV and the immune system primed to fight the disease, it is reasonable to think that the COVID-19 vaccine would also protect humans from the severe COVID-19 disease, the scientists say.

Next steps

Additional testing – including human trials – would be needed before the COVID-19 vaccine could be approved by the federal Food and Drug Administration or other regulatory agencies around the world for use in humans, but employees are pleased with the early successes of the vaccine development platform.

Zeichner added that he was encouraged that a collaboration between UVA and Virginia Tech, schools with a known sports rivalry, has produced such promising results.

“XJ is just a great employee and a great scientist. And he is incredibly generous with his time and the resources at his disposal, ”said Zeichner. “If scientists from UVA and Virginia Tech can work together to do something positive to address the pandemic, there may be some hope for collaboration and collaboration in the country as a whole.”

About the research

The researchers have published their findings in the scientific journal PNAS. The findings are peer-reviewed. The research team included 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.

Reference: “Killed Whole Genome Reduced-Genome Coronavirus Vaccines Protect Against Diseases in a Pig Model” by Denicar Lina Nascimento Fabris Maeda, Debin Tian, ​​Hanna Yu, Nakul Dar, Vignesh Rajasekaran, Sarah Meng, Hassan M. Mahsoub, Harini Sooryanarain, Bo Wang, C. Lynn Heffron, Anna Hassebroek, Tanya LeRoith, Xiang-Jin Meng, and Steven L. Zeichner, April 15, 2021, Proceedings of the National Academy of Sciences.
DOI: 10.1073 / pnas.2025622118

Zeichner is the McClemore Birdsong professor in the departments of Pediatrics and Microbiology, Immunology and Cancer Biology, the director of the Pendleton Pediatric Infectious Disease Laboratory, and part of the UVA Children’s Child Health Research Center. Meng is a University Distinguished Professor and Member of Virginia Tech’s Department of Biomedical Sciences & Pathobiology.

Their vaccine development work was supported by the Pendleton Pediatric Infectious Disease Laboratory, the McClemore Birdsong Endowed Chair, and generous support from the University of Virginia Manning Fund for COVID-19 Research and the Ivy Foundation. The work was also supported in part by the Virginia-Maryland College of Veterinary Medicine (FRS # 175420) and Virginia Tech internal funds (FRS # 440783).