Wednesday, September 15, 2021

A rare Tibetan worm may hold key to long-acting COVID vaccines


Caterpillars with emerging Ophiocordyceps sinensis
Credit: William Rafti Institute
A molecule isolated from the world’s most valuable parasite, the caterpillar fungus (Ophiocordyceps sinensis), may provide clues to better and more stable mRNA vaccines, according to research being done in Australia.

The molecule was first isolated from cordyceps fungi in the 1950s. These fungi infect ghost moth larvae, to make 'summer grass' prized in Tibetan and Chinese medicines for its benefits as a tonic and as a treatment for sexual dysfunction.

Associate Professor Traude Beilharz, from the Biomedicine Discovery Institute at Monash University in Melbourne, and her team have been studying the cordycepin molecule because of its ability to trick cells into increasing nucleotides and making mRNA with longer 3'UTRs. According to Associate Professor Beilharz, understanding how 3' UTRs work is really important to improving the stability and function of vaccines. Their research was recently published in the eLife journal.

The lab is now using what they have learned about 3'UTRs from that study to create a screening

Associate Professor Traude Beilharz

platform to identify optimal 3'UTRs for new mRNA vaccines. These 3’UTRs are crucial in stimulating immunity and may reduce the need for booster shots to maintain this immunity. Rachael Turner, first author of the study, has nearly completed her PhD thesis. Next she will apply her expertise in 3’ UTR function toward improving future mRNA vaccines.

The caterpillar fungus, Ophiocordyceps sinensis, is the world’s most valuable parasite. It’s a relative of the tropical fungus that turns ants into zombies, but unlike its infamous cousin, it is found only on the Tibetan plateau, where it infects the larvae of ghost moths. It has long been part of traditional Chinese medicine, and demand for it has risen so sharply in recent decades that in Beijing it is now worth three times its weight in gold. In Bhutan, one of the countries where the fungus is harvested, it accounts for a significant slice of the gross domestic product.

The development of mRNA vaccines, largely due to COVID-19, has been rapid. In addition, the development of mRNA vaccines against cancer has also developed at pace. According to Associate Professor Beilharz, “mRNA vaccines are a promising technology as the production process is simple, safety profiles are better than those of DNA vaccines, and mRNA-encoded antigens are readily expressed in cells, which stimulate immunity against the virus.”

However, mRNA vaccines also possess some inherent limitations. While side effects such as allergy, renal failure, heart failure, and infarction remain a risk, the vaccine mRNA may also be degraded quickly after administration, leading to the need for boosters.

The best types of mRNA vaccines are those that only encode the target antigen (in the case of COVID vaccines, the spike protein) and contain 5' and 3' untranslated regions (UTRs), which provide comprehensive stimulation of the adaptive and innate immunity. “Studying the cordyceps fungi molecule and how it can be used to understand the function of 3’UTRs is a key step in making better vaccines against infectious diseases like COVID-19 and also cancers,” Associate Professor Beilharz said.

Monash is home to Australia's largest network of RNA and mRNA researchers. Keep up to date with our work on life-saving vaccines and therapeutic treatments on the Monash RNA webpage.

Source/Credit: Monash University