UVA, Va. Tech Virologists Develop Potential Broadly Protective Coronavirus Vaccines

Innovative Approach to Vaccine Development Could Lead to Vaccine Protecting Against Many Coronaviruses, Including COVID-19

Newswise — CHARLOTTESVILLE, Va., March 24, 2021 – A COVID-19 vaccine that could provide protection against both existing and future strains of the COVID-19 virus, and other coronaviruses, and cost about $1 a dose has shown promising results in early animal testing. 

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

Their coronavirus vaccine offers several advantages that could overcome major obstacles to global vaccination efforts. It would be easy to store and transport, even in remote areas of the world, and could be produced in mass quantities using existing vaccine-manufacturing factories. 

The UVA and Virginia Tech scientists created the vaccine using a new platform Zeichner invented to rapidly develop new vaccines. So the testing success bodes well for both the COVID-19 vaccine and Zeichner’s vaccine-development approach. 

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

 

A New Vaccine-Development Approach 

Zeichner’s new vaccine-production platform involves synthesizing DNA that directs the 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 another small circle of DNA called a plasmid that can reproduce within bacteria. The plasmid is then introduced into bacteria, instructing the bacteria to place pieces of proteins on their surfaces. The technique uses the common bacteria E. coli

One major innovation is that the E. coli have had a large number of its genes deleted. Removing many of the bacteria’s 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 simply grown in a fermenter, much like the fermenters used in common microbial industrial processes like brewing, and 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 said. “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 two to three weeks, making the platform ideal for responding to a pandemic.

 

Targeting COVID-19 

Zeichner and Meng’s vaccine takes an unusual approach in that it targets a part of the spike protein of the virus, the “viral fusion peptide,” that is essentially 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 that causes COVID-19, that have been obtained from thousands of patients around the world during the pandemic.

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, but they are distant relatives. PEDV and SARS-CoV-2, like all coronaviruses, share several of the amino acids that constitute the fusion peptide. 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 US, it killed almost 10% of US pigs – a pig pandemic.

One advantage of studying PEDV in pigs is that Meng and Zeichner could study the ability of the vaccines to offer protection against a coronavirus infection in its native host – in this case, pigs. The other models that have been 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. Pigs are also very similar in physiology and immunology to people – they may be the closest animal models to people other than 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 protected the pigs against disease caused by PEDV and primed the immune system to fight the disease, it is reasonable to think that the COVID-19 vaccine would also protect people against severe COVID-19 disease, the scientists say.

 

Next Steps 

Additional testing – including human trials – would be required 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 people, but the collaborators are pleased by 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 well-known sports rivalry, has produced such promising results.

“XJ is just an amazing collaborator and a wonderful scientist. And he is incredibly generous with his time and the resources he has available,” Zeichner said. “If UVA and Virginia Tech scientists can work together to try to do something positive to address the pandemic, then maybe there is some hope for collaboration and cooperation in the country at large.”

 

About the Research

The researchers have described their findings in a preprint: https://biorxiv.org/cgi/content/short/2021.03.15.435497v1. 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 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.

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

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

 

 

 

####

UVA Health is an academic health system that includes a 696-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

SEE ORIGINAL STUDY



Filters close

Showing results

110 of 5861
Released: 23-Jun-2021 12:10 PM EDT
Phone swabs can accurately detect COVID-19
University College London

An accurate, non-invasive, and low-cost method of testing for COVID-19 using samples taken from the screens of mobile phones has been developed by a team led by UCL researchers at Diagnosis Biotech.

Newswise: NIH study suggests COVID-19 prevalence far exceeded early pandemic cases
Released: 23-Jun-2021 11:35 AM EDT
NIH study suggests COVID-19 prevalence far exceeded early pandemic cases
National Institute of Biomedical Imaging and Bioengineering

In a new study, NIH researchers report that the prevalence of COVID-19 in the United States during spring and summer of 2020 far exceeded the known number of cases and that infection affected the country unevenly.

Released: 23-Jun-2021 11:25 AM EDT
Half of young adults with covid-19 have persistent symptoms 6 months after
University of Bergen

A paper published in the prestigious journal Nature Medicine on long-COVID, describes persistent symptoms six months after acute COVID-19, even in young home isolated people.

Newswise:Video Embedded covid-19-vaccine-hesitancy-dr-vin-gupta-narrates-new-american-thoracic-society-video
VIDEO
Released: 23-Jun-2021 9:40 AM EDT
COVID-19 Vaccine Hesitancy: Dr. Vin Gupta Narrates New American Thoracic Society Video
American Thoracic Society (ATS)

The American Thoracic Society rolls out a new video to address vaccine hesitancy and answer common questions amid the COVID-19 pandemic.

18-Jun-2021 11:00 AM EDT
Had COVID-19? One Vaccine Dose Enough; Boosters For All, Study Says
American Chemical Society (ACS)

A new study in ACS Nano supports increasing evidence that people who had COVID-19 need only one vaccine dose, and that boosters could be necessary for everyone in the future.

Released: 22-Jun-2021 5:10 PM EDT
Tecnología de inteligencia artificial y ECG puede rápidamente descartar infección por COVID-19
Mayo Clinic

La inteligencia artificial puede ofrecer un manera de determinar con exactitud que una persona no está infectada con la COVID-19. Un estudio internacional y retrospectivo descubrió que la infección por SARS-CoV-2, el virus que causa la COVID-19, provoca sutiles cambios eléctricos en el corazón. Un electrocardiograma (ECG) mediado por inteligencia artificial detecta estos cambios y puede servir como una prueba rápida y confiable para descartar la infección por COVID-19.

Released: 22-Jun-2021 4:45 PM EDT
Penn Medicine to Use $1M from City of Philadelphia for Additional Community Vaccination Clinics
Perelman School of Medicine at the University of Pennsylvania

Penn Medicine will continue its collaboration with the West and Southwest Philadelphia communities to operate a series of COVID-19 vaccine clinics in partnership with community organizations, faith-based institutions, restaurants, barbershops, and even professional sports teams thanks to $1 million in funding from the City of Philadelphia, in partnership with PMHCC.

Released: 22-Jun-2021 12:30 PM EDT
Political Variables Carried More Weight Than Healthcare in Government Response to COVID-19
Binghamton University, State University of New York

Political institutions such as the timing of elections and presidentialism had a larger influence on COVID-19 strategies than the institutions organizing national healthcare, according to a research team led by a professor at Binghamton University, State University of New York.

22-Jun-2021 12:00 PM EDT
Study Testing How Well COVID-19 Vaccine Prevents Infection and Spread of SARS-CoV-2 Among University Students Now Expands to Include Young Adults Beyond the University Setting
Covid-19 Prevention Network (CoVPN)

The Prevent COVID U study, which launched in late March 2021 to evaluate SARS-CoV-2 infection and transmission among university students vaccinated with the Moderna COVID-19 Vaccine, has expanded beyond the university setting to enroll young adults ages 18 through 29 years and will now also include people in this age group who choose not to receive a vaccine.

Newswise: First Wave COVID-19 Data Underestimated Pandemic Infections
18-Jun-2021 8:30 AM EDT
First Wave COVID-19 Data Underestimated Pandemic Infections
American Institute of Physics (AIP)

Two COVID-19 pandemic curves emerged within many cities during the one-year period from March 2020 to March 2021. Oddly, the number of total daily infections reported during the first wave is much lower than that of the second, but the total number of daily deaths reported during the first wave is much higher than the second wave.


Showing results

110 of 5861

close
1.53929