Researchers developing Australia’s first mRNA Covid vaccine say they may have solved the “immune imprinting” issue that has contributed to the declining effectiveness of boosters as the virus mutates.
Immune imprinting, also known as original antigenic 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, being developed by the Monash Institute of Pharmaceutical Sciences (MIPS) in collaboration with the Doherty Institute, aims to tackle the problem by encoding the 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 Development, the researchers tested their mRNA ‘membrane-anchored receptor-binding domain’ (mRNA RBD-TM) vaccine 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 for the mRNA RBD-TM vaccine compared with 1.3 for the ancestral vaccine, despite previous exposure to the SARS-CoV-2 virus, suggesting the potential to overcome immune imprinting.
“The concept of immune imprinting is not a new one — the same phenomenon occurs with influenza, and there is now mounting evidence of widespread imprinting attributed to exposure to ancestral Covid-19 strains,” Professor Colin Pouton from MIPS said in a statement.
“To address this, we developed an alternative platform designed to target SARS-CoV-2 virus mutations in the tip of the ‘spike’, otherwise known as the receptor binding domain. We found that, when administered as a third-dose booster following two doses of ancestral vaccine … our vaccine was able to effectively induce new variant-specific antibodies, making it a promising next-generation candidate to protect against new and emerging Covid-19 strains.”
Prof Pouton said next-generation Covid vaccines were needed to protect ageing 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 developing a new refined, homegrown vaccine to protect against Covid-19.
“Another advantage to the mRNA RBD-TM vaccine is that, because it’s about a quarter of the size of its whole-spike equivalents, it could be effective at lower doses, therefore making it more tolerable,” he said.
“Its smaller mRNA size also means it can be more stable at higher storage temperatures, a feature important for future mRNA vaccines.”
Professor Damian Purcell from the Doherty Institute said, “Our 20 years of prior University of Melbourne research on prototype RNA vaccines and on protective antiviral immunity encouraged us to prioritise rigorous research and development of the Monash mRNA RBD-TM vaccine candidate.
“We used our broad resources to demonstrate that safe and effective immune responses were generated in mice against new immune-evading variant virus isolates.”
The MIPS Covid-19 mRNA vaccine has already completed a phase one clinical trial as a fourth-dose booster.
Prof Pouton said ideally the next step would be to test the mRNA RBD-TM candidate in clinical trials to further validate its effectiveness as a next generation Covid vaccine to address immune imprinting.
Monash University’s Covid vaccine was the first mRNA vaccine candidate developed and manufactured 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 hub in the Asia-Pacific for mRNA and RNA research, commercialisation, advanced manufacturing and workforce training”.
Messenger RNA (mRNA), a type of single-stranded molecule involved in protein synthesis, has been researched for decades but was not widely used until the Covid vaccines.
The technology is now being applied to a range of other illnesses 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 on the construction of an mRNA vaccine manufacturing facility in Clayton, capable of producing up to 100 million vaccine doses per year.
The Australian government currently recommends a booster dose every six months for everyone aged 75 and older, every 12 months for those aged over 65, and every 12 months for over 18s with severe immunocompromise.
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 December 11.
The latest Health Department figures show 18.5 per cent of over-75s have had a booster in the last six months, 9.6 per cent of those aged 65 to 74, and just 1.8 per cent of over-18s.
