Australia’s first mRNA vaccine candidate for Covid could solve ‘immune imprinting’ problem

Researchers developing Australia’s first mRNA Covid vaccine say they may have solved the issue of “immune imprinting” that has contributed to the decline in effectiveness of boosters as the virus mutates.

Immune imprinting, also known as antigenic original sin, occurs when the body’s original immune response to a virus – either from vaccination or infection – becomes less effective against new variants of the same virus.

The Australian-based vaccine candidate, developed by the Monash Institute of Pharmaceutical Sciences (MIPS) in collaboration with the Doherty Institute, aims to tackle the problem by encoding proteins on the surface of the receptor-binding domain – the tip of the virus ‘spike’.

In a preclinical study, published in Molecular therapy methods and clinical developmentresearchers tested their “membrane-anchored receptor-binding domain” mRNA vaccine (RBD-TM mRNA) against ancestral Covid vaccines by comparing third-dose immune responses to Omicron variants in mice.

The study showed a 16.3-fold increase in antibodies to the RBD-TM mRNA vaccine compared to 1.3 for the ancestral vaccine, despite prior exposure to the SARS-CoV-2 virus, suggesting the potential to overcome immune entrainment.

“The concept of immune imprinting is not new – the same phenomenon occurs with influenza, and there is now growing evidence of widespread suppression attributable to exposure to ancestral Covid-19 strains,” said Professor Colin Pouton from MIPS. a statement.

“To address this, we developed an alternative platform designed to target mutations of the SARS-CoV-2 virus at the tip of the ‘spike,’ otherwise known as the receptor binding domain. We found that, when administered as a third-dose booster after two doses of the ancestral vaccine—our vaccine was able to effectively induce new variant-specific antibodies, making it a promising candidate for next generation to protect against new and emerging Covid 19 strains.â€

Prof Pouton said next-generation Covid vaccines were needed to protect elderly and vulnerable populations from future mutant strains of the virus.

Lead author Dr Harry Al-Wassiti said the study could help pave the way for the development of a new, refined, home-grown vaccine to protect against Covid-19.

“Another advantage of the RBD-TM mRNA vaccine is that, because it is about one-fourth the size of its full-length equivalents, it can be effective at lower doses, making it more tolerable,” he said. .

“Its smaller mRNA size also means it can be more stable at higher storage temperatures, an important feature for future mRNA vaccines.”

Professor Damian Purcell from the Doherty Institute said: “Our previous 20 years of research at the University of Melbourne on prototype RNA vaccines and on protective antiviral immunity encouraged us to prioritize rigorous research and development of the mRNA vaccine candidate Monash RBD-TM.

“We used our extensive resources to demonstrate that safe and effective immune responses were generated in mice against novel isolates of immune-evading virus variants.”

The MIPS Covid-19 mRNA vaccine has already completed a phase 1 clinical trial as a fourth dose booster.

Prof Pouton said ideally the next step would be to test the RBD-TM mRNA candidate in clinical trials to further prove its effectiveness as a next-generation Covid vaccine to address immune entrainment.

Monash University’s Covid vaccine was the first mRNA vaccine candidate developed and produced for clinical trials in Australia, funded by the Victorian Government through mRNA Victoria.

Established in May 2021, mRNA Victoria aims to turn the state into “the leading center in the Asia-Pacific for research, commercialisation, advanced manufacturing and training of the mRNA and RNA workforce”.

Messenger RNA (mRNA), a type of single-stranded molecule involved in protein synthesis, has been researched for decades but was not widely used until Covid vaccines.

The technology is now being applied to a number of other diseases including infectious diseases, Alzheimer’s and cancer.

mRNA Victoria has so far funded 57 research projects for a total of nearly $29 million and has partnered with Moderna to build an mRNA vaccine manufacturing facility in Clayton capable of producing up to 100 million doses of vaccine per year.

The Australian government currently recommends a booster dose every six months for everyone aged 75 and over, every 12 months for those over 65 and every 12 months for severely immunocompromised over 18s.

Adults without severe immunocompromise and children aged five to 17 with severe immunocompromise are eligible for a booster every 12 months.

A total of 930,000 doses were administered in the six months to 11 December.

The latest Department of Health figures show 18.5 per cent of people over 75 have had a booster in the past six months, 9.6 per cent of those aged 65 to 74 and just 1.8 per cent of people over 18.