The team of scientists behind Australia’s first mRNA COVID-19 vaccine have published a preclinical study demonstrating the vaccine’s potential to overcome the issue of ‘immune imprinting.’
Immune imprinting occurs when exposure to one virus strain – acquired by way of either vaccination or viral infection – starts to limit our immunity against new variants of the virus as they arise.
Led by the Monash Institute of Pharmaceutical Sciences (MIPS) in collaboration with the Peter Doherty Institute for Infection and Immunity (Doherty Institute), the researchers focused on tackling immune imprinting by testing a vaccine designed to encode the proteins on the surface of the receptor-binding domain (the tip of the virus ‘spike’).
In mice, the team tested their mRNA ‘membrane-anchored receptor-binding domain’ (mRNA RBD-TM) vaccine against ancestral COVID vaccines by looking at third-dose immune responses to Omicron variants.
The study showed the mRNA RBD-TM vaccine induced a significantly stronger antibody response than ancestral vaccines (antibody fold increase for ancestral vaccine was 1.3, compared with a 16.3 fold-increase for the mRNA RBD-TM vaccine), despite previous exposure to SARS-CoV-2, thus suggesting the potential to overcome the detrimental effects of immune imprinting.
Corresponding author, Professor Colin Pouton from MIPS, said to protect ageing and vulnerable populations from future infections by evasive mutants, next generation COVID-19 vaccines will need to overcome the problem of 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 Pouton said.
“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 (in mice), 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.”
First author, Dr Harry Al-Wassiti – who was pivotal to the development of the MIPS vaccine – said the new 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. Its smaller mRNA size also means it can be more stable at higher storage temperatures, a feature important for future mRNA vaccines,” Dr Al-Wassiti said.
Professor Damian Purcell, Head of Molecular Virology at the Doherty Institute and a senior author on the study said collaboration has been key to getting the vaccine candidate to this point.
“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,” Professor Purcell said.
The MIPS COVID-19 mRNA vaccine has already completed a Phase 1 clinical trial, in partnership with the Doherty Institute, as a fourth-dose booster against COVID-19. Professor 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-19 vaccine to address immune imprinting.
Monash’s COVID-19 vaccine was the first example of an mRNA vaccine candidate developed and manufactured for clinical trials in Australia, thanks to funding provided by the Victorian Government through mRNA Victoria, a dedicated government agency established to lead mRNA research, development, and advanced manufacturing capability to establish a world-class Australian mRNA and RNA industry, based in Victoria.
The study is published in Molecular Therapy Methods and Clinical Development.
