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U.Va. research team contributes to development of universal coronavirus vaccine

Researchers at the University and Virginia Tech are developing a new approach to a bacteria-based vaccine


The University’s School of Medicine and Virginia Tech are developing a widely-accessible universal vaccine that has the potential to protect against many different coronavirus disease strains. 

COVID-19 is still a prominent influence in the lives of people around the world and has heavily affected countries with weaker economies who struggle to mitigate the spread of the virus as vaccination efforts are significantly challenged by little to no domestic production of vaccines.

For these reasons, Steven Zeichner, infectious diseases specialist and lead researcher, said it is important to create a vaccine that is cheap and easy to produce.

“Our approach was [asking] what would be the ideal goals of a vaccine, especially for use globally in poor countries,” Zeichner said. 

Zeichner explained how the team’s goal is not to take away from or discredit existing vaccines, but rather expand upon the original vaccine concept from a different perspective.

The existing COVID-19 vaccines — namely Pfizer and Moderna — inject mRNA into the upper arm, where the cells use the instructions from the mRNA to make a protein piece found on the surface of the COVID-19 virus. This spike protein is what allows the virus to penetrate host cells and cause infection. The protein triggers an immune response, training the body in how to fight off the virus if it were ever to be introduced again — for example, if the individual were exposed to COVID-19. 

Conversely, the Johnson & Johnson vaccine uses a disabled adenovirus that is not related to coronavirus. Unlike mRNA vaccines, Johnson & Johnson does not require extremely cold temperatures for its storage. 

The universal aspect of this new vaccine stems from the fusion peptide, a sequence of amino acids that cannot mutate and is found in all coronavirus variants. Fusion peptides allow viruses to bring their membranes into contact with the membrane of the host cell in order to deposit genetic information and replicate, causing disease. This peptide is an integral component of the viral life cycle, particularly for membrane functionality. 

The method Zeichner and his team have developed involves using bacteria instead of viral mRNA. The starting material of the vaccine is purely a culture of bacteria and a growth medium, like yeast extract, which promotes cell proliferation. The vaccine antigen is placed on the surface of the inactive bacteria, and the bacteria itself is incubated and grown, resulting in the final vaccine.

A benefit of this method is the inexpensive production of plasmids — an extrachromosomal DNA molecule that can replicate independently — used in the bacterial transformation. 

Biotechnology companies — such as GeneWiz, used by Zeichner’s research team — can synthesize DNA at just fifteen cents per base pair. The synthetic gene is added to a plasmid, which is then cloned many times. The plasmids will modify the bacteria culture by adding recombinant vaccine proteins onto the surface of bacteria. This allows for the inactivated bacteria itself to be injected into the body and to function as a vaccine by teaching the immune system how to fight off the specific illness.

In mitosis, the passenger protein facilitates the split of a cell after the chromosomes separate by controlling the attachment of spindle fibers to the chromosomes.

“So subject to some limitations, you can replace coding sequence for the passenger protein with coding sequence for some other protein — for example, a vaccine antigen — which means that you can then put coding sequence for a vaccine antigen into this plasmid and get it to express the antigen on the surface of the bacteria,” Zeichner said.

Through this process known as an expression cassette, up to about 200,000 vaccine antigens can be expressed on the surface of every bacteria, which translates to easier mass production. 

“If we pull this out, express it with our system, we can focus the immune system on this little piece and get it to make an immune response that's going to cover all sorts of different variants,” Zeichner said. 

These new vaccines cost less than one dollar per dose, which is crucial because a third of the world lives on less than $5 a day. Additionally, mRNA vaccines are difficult to make, biologically and logistically. They require complex transcription processes and designated factories at which each step is completed. The ability to produce such an elaborate vaccine takes the resources of multi-billion dollar companies, which many countries do not have.

“The other thing that people need to think about is that trying to get vaccines for COVID, for everyone in the world, is not charity — it's self-defense,” Zeichner said.

A specific timeline for the vaccine does not yet exist. However, if this new vaccine continues its success with protecting against coronaviruses in future studies, many poorer countries will be able to produce this vaccine domestically with existing technologies, since it can be done in a research lab setting. 

Zeichner discussed the partnership between his team and the International Vaccine Institute in South Korea, which is part of the World Health Organization. The main purpose of this institute is to develop vaccines for poorer countries in the world through wholesale production, and the new bacteria vaccine fits well into their technical capabilities. 

Zeichner and his team, including researchers at Virginia Tech, are planning to further their work through this collaboration by testing on mice and planning early stage clinical trials. 

“With our partners at Virginia Tech — our great collaborator [Xiang-Jin] Meng — we made a vaccine against SARS-CoV-2 fusion peptide and porcine epidemic diarrhea virus fusion peptide,” Zeichner said. “This six amino acid sequence in the middle of the fusion peptide is ... completely ... conserved among all coronaviruses that have ever been sequenced.”

Currently, Zeichner and his team are focused on acquiring more funding for their research and working towards conducting human trials. Zeichner emphasizes the strong discipline it requires to pursue such novel research and the importance of not being discouraged by the inevitable setbacks.

“The key is to try to understand how it fails and to fix it so it doesn't fail the next time.” Zeichner said.