- Using bio-engineered yeast, the common single-celled fungal cells used by bakers, a team of researchers led by a Filipino-American scientist hopes to transform COVID into a common cold.
- 'The goal from this scrappy vaccine is not to prevent you from getting COVID. It’s actually to prevent you from getting severe COVID that will require hospitalisations,' says scientist-priest.
- Yeast-based vaccine does not require intramuscular injection — it can be administered orally (like the oral polio vaccine).
Dubai: A Filipino-American scientist hopes to beat the coronavirus with a vaccine developed using baker’s yeast. By using bio-engineered yeast, the common single-celled fungal cells, Rev. Nicanor Austriaco hopes to transform COVID into a common cold. “The goal from this scrappy vaccine is not to prevent you from getting COVID. It’s actually to prevent you from getting severe COVID that will require hospitalisations,” the churchman-scientist told Gulf News.
Rev. Austriaco, 52, earned his doctorate degree in yeast molecular biology from the Massachusetts Institute of Technology (MIT). His COVID-19 shot is currently in pre-clinical development in the US. A license to conduct clinical trials will be sought in the Philippines, the home of his ancestors, after the “mouse work” (test on animals), he added. He currently consults with the Manila government on the coronavirus pandemic response.
Upshots for a yeast-based vaccine
- It doesn’t require refrigeration, and will remain shelf-stable, making it ideal for developing countries.
- It does not require intramuscular injection — it can be administered orally (like the oral polio vaccine).
- Can be more widely distributed among the poorest of the poor, especially in the hard-to-reach places of the planet.
• It lives on the outside of wheat, fruits, lentils, etc.
• The earliest historical evidence of the use of yeast by humans goes back 10,000 BCE.
• Yeast takes sugar and converts it into carbondioxide, before turning them into alcohol.
• Yeast has been used in understanding medicine, as its cells have a lot of properties that look like human cells.
About a dozen COVID-19 vaccines had already been approved in different jurisdictions; dozens more are under development, though initial shortfalls in vaccine supplies had been reported due to the sheer demand. None of the approved COVID-19 vaccines uses yeast as a development or delivery platform.
Path to yeast vaccine?
It’s not a straight path to success. Vaccine researchers and producers are all racing against time to test its viability. The method goes something like this: take the coronavirus (or strains that cause severe infections and deaths), introduce some of its properties (like the spike protein) into yeast, and have the yeast (specifically, Saccharomyces cerevisiae) multiply the virus.
With programmed cell death in yeast, the virus dies too, so then you can administer it as a vaccine (to train the body to recognise the pathogen in it, now dead, but still able to kick up antibodies so they’re ready when the real thing comes).
As a molecular biologist, Austriaco’s specialisation is "programmed yeast cell death”. He says his planned COVID jab can be orally taken. He currently runs his own research lab (Austriaco Labs).and is set to open a COVID-19 vaccine research lab at the University of Santo Tomas (UST) in Manila, Philippines.
This process is therefore called programmed cell death, although it is more commonly called apoptosis (from a Greek word meaning “falling off,” as leaves from a tree).
He's not alone in this endeavour. On May 4, 2020, Nature published a study done by researchers in Switzerland who managed to generate a “full-length clone” SARS-CoV-2 genome with rapid, yeast-based method. The team reported on the use of yeast artificial chromosomes as enabler for the “rapid genetic reconstruction of the deadly coronavirus”.
In virology, reconstructing and modifying the genomes of disease-causing viruses is the starting point of many research endeavours. These genetic manipulations are essential for studying a virus’s method of infection, its replication, drugs that might work against it, and potential vaccines.
Hope for yeast, inexpensive vaccine?
The use of yeast is not new. The record of human use of yeast goes back at least 10,000 years. In recent years, scientists had been investigating its utility as a vaccine development platform,
For example, in March 2020, Chinese experts led by Dr Han Lei (of China’s Southwest Jiaotong University, in Chengdu), published in Microbial Cell Factory results of a study on the use of yeast as display platform technology to prepare oral vaccines against lethal H7N9 virus challenge in mice.
My hope is this vaccine, because it is shelf-stable, you can actually keep it in your shelf, it does not require refrigeration, it does not require injection, it does not require a nurse, it does not require a doctor.
“My hope is this vaccine, because it is shelf-stable, you can actually keep it in your shelf, it does not require refrigeration, it does not require injection, it does not require a nurse, it does not require a doctor, that would be the vaccine that would allow the Philippines to vaccinate the poorest of the poor, as well as those who are living in the far-flung islands of our archipelago,” he said.
On the cost front, he also hopes this vaccine would be “available to the them cheaply, but would still be safe and efficacious.”
What’s the value of yeast in COVID vaccine research?
To learn about a virus, scientists usually put together DNA fragments and introduce them into Escherichia coli bacteria for replication — one of the most common methods for cloning viral genomes. While there are advantages in doing this, there’s one major downside: for some viruses (including those from the Coronavirudae family, like SARS-CoV-2), this method is cumbersome.
Reason: coronaviruses have relatively large genomes, explained Volker Thiel of the University of Bern, in Switzerland, who formed part of the team that published their study in Nature. This makes them (coronaviruses) difficult for the bacteria to cope with. Moreover, parts of the genome are unstable or can be toxic to the bacteria.
Enter yeast: Their cells are larger than bacteria, so they can handle bigger pieces of DNA. Another big advantage offered by yeast: their cells have an inherent ability to assemble fragments of DNA into one big molecule.
What does this mean?
For virologists, it means instead of having to reconstruct the viral DNA first before introducing it into cells, “you can instead put all these fragments in the yeast and it magically puts them together,” microbiologist and coronavirus expert Susan Weiss of the University of Pennsylvania Perelman School of Medicine told The Scientist. She did not form part of the Swiss-led research team. “The exciting thing about the yeast is that ... it’s fast. The other methods are tedious and difficult,” added Dr Weiss.
What is yeast artificial chromosome (YAC)?
Yeast naturally allows for automatic fragment assembly, the core of the cloning method used by researchers. It is also known as transformation-associated recombination (TAR). To reconstruct SARS-CoV-2, a Swiss-led research team who reported their work in Nature used 14 fragments of DNA representing the entire SARS-CoV-2 genome. Each fragment shared a short region of overlapping sequence with the next.
The researchers explained that the two end fragments of the genome also shared overlapping sequences with a plasmid “vector” that would contain the viral genome and allow it to form a yeast artificial chromosome (YAC).
This gluing process (“homologous recombination”) — involves trimming away nucleotides at the end of one strand of DNA and annealing the remaining complimentary sequences (the overlapping section) to another fragment. The capacity to recombine things to a YAC by themselves is just amazing,” says Joerg Jores, one of the study authors.
Encouraging people to vaccinate
On social media, Rev. Austriaco, stresses his belief in the COVID-19 vaccine and its benefit to society. He encourages people to receive a coronavirus vaccine, and rues the high velocity of anti-vaxx disinformation and misinformation on social media platforms.
COVID-19 vaccine will help save lives as well as slow social disruptions and lockdowns, which will help society return to a level of normalcy.
‘Vaccine scientists did not start from scratch’
Austriaco has dispelled high-velocity fear-mongering, especially on social media, by the anti-vaxx camp, especially regarding the speed by which the vaccines were developed. He pointed to the fact that RNA viruses, including the coronavirus subclass (Coronaviridae), have been studied for decades. Even the messenger RNA technology was not developed overnight, he explained. The development of mRNA vaccines (Pfizer/BioNTech and Moderna), started about 50 years ago.
“I trust the scientific process that has gone into the development and testing of these vaccines. These vaccines rely on decades of research. It is not like scientists just woke up one morning at the beginning of the pandemic and started from scratch.”
They were developed in record time because scientists had unlimited funding by governments who are seeking to resolve a global pandemic and its negative effect on every country’s economy.
The scientist-priest also dispelled medical rumours about vaccine side effects, such as allergic reactions. He said the vaccine has known minor side effects — like a slight fever and a feeling of exhaustion. He explained that these are, in fact, signs that the process is working and the vaccine is jumpstarting the immune system.
Before he became a priest, Rev. Austriaco trained as a scientist. In 1989, he completed his Bachelor’s Degree (B.S.E.) in Bioengineering (summa cum laude) at the University of Pennsylvania. In 1996, he earned his doctorate in Biology from MIT. He was ordained a priest in May of 2004 (also completed Moral Theology, summa cum laude, at the Dominican House of Studies in Washington, DC, in 2005). He did Pontifical Doctorate in Sacred Theology, magna cum laude, at the University of Fribourg in Switzerland, in 2015.
As a researcher, Fr. Austriaco has team up with top scientists whose work had been peer-reviewed and published in scientific journals. Papers describing his research have been published in PLoS ONE, FEMS Yeast Research, Microbial Cell, Cell, the Journal of Cell Biology, and the Proceedings of the National Academy of Sciences (PLoS USA), among others. His NIH-funded laboratory at Providence College is investigating the genetics of programmed cell death using the yeasts, Saccharomyces cerevisiae and Candida albicans, as model organisms.
Fr. Austriaco currently serves as Professor of Biology and Theology at Providence College in Providence, Rhode Island (US). He is also currently a research fellow at the Center for Religious Studies and Ethics at the University of Santo Tomas in Manila, Philippines, and a consultant of the Philippine government.
His book, Biomedicine and Beatitude: An Introduction to Catholic Bioethics, was published in 2011