Clinical trial commences for Melbourne-made COVID vaccines

Researchers are looking for 114 healthy people aged 18–70 living in Victoria to roll up their sleeves for a Phase 1 clinical trial of two Melbourne-made COVID-19 vaccines.

The two vaccine candidates, created by researchers at the Peter Doherty Institute for Infection and Immunity and the Monash Institute of Pharmaceutical Sciences (MIPS), are distinct from existing vaccines because they focus the immune response on the tip of the SARS-CoV-2 spike protein, called the receptor binding domain (RBD). The RBD enables the virus to enter and infect cells in the body and elicits over 90% of neutralising antibodies (antibodies that can block the virus) following SARS-CoV-2 infection.

The two candidates are:

• RBD protein vaccine — This uses part of the virus protein, rather than genetic material or another virus, to elicit an immune response.
• RBD mRNA vaccine — This represents the virus genetic sequence that codes for the tip of the spike, which will lead to production of the RBD protein.
   

They are ‘proof of principle’ variant vaccines that present the Beta variant to the immune system, which was of the greatest concern when these vaccines were designed. Furthermore, the Beta variant has two of the same key RBD mutations as the Omicron variants (BA.1 and BA.2), so they may also improve immunity to Omicron.

The Phase 1, first-in-human trial will assess the safety and efficacy of a single dose of the vaccines as a fourth dose of a COVID-19 vaccine; therefore, participants must have had their third dose at least three months prior to the study commencing. People who have been infected with COVID-19 are also eligible provided they had their infection at least three months prior, and have had their third vaccine dose.

The trial will be led by Professor Terry Nolan, Head of the Vaccine and Immunisation Research Group at the Doherty Institute. He said, “What’s … unique about this gold-standard, randomised, double-blind, placebo-controlled trial is that it will be the first time a side-by-side comparison will be undertaken of two new COVID-19 vaccine platforms.”

Dr Georgia Deliyannis, who performed most of the RBD protein vaccine experiments at the Doherty Institute, said in preclinical trials the vaccine induced high levels of RBD-specific antibodies, including high neutralising antibodies, following two doses.

“Immunity induced by the RBD protein vaccine protects against virus challenge in a mouse model of SARS-CoV-2 infection, even 100 days following the boost,” Dr Deliyannis said.

“As well as inducing strong neutralising antibody immunity to the Beta variant in mice, it also retains its potential to neutralise the original ancestral strain, and preliminary in-lab studies have demonstrated neutralising activity against other variants including Delta and Omicron.”

MIPS Professor Colin Pouton, who led the development of the RBD mRNA vaccine, said the team used similar strategies to formulate and manufacture the vaccine to those used by other global biotech manufacturers, but designed the mRNA to focus on the RBD in alignment with the RBD protein vaccine.

“In common with the RBD protein vaccine, the RBD mRNA vaccine induced high levels of RBD-specific antibodies and protected against virus challenge in the mouse model,” Prof Pouton said. “We have good reason to think that both vaccines will perform well in the clinic.”

Professor Sharon Lewin, Director of the Doherty Institute, said with millions more doses of COVID-19 vaccines still to be administered globally, and new variants arising, next-generation vaccines with innovative technology are required.

“Both vaccines are efficient to produce and can be rapidly modified to incorporate distinct or multiple RBD mutations arising in future variants,” Prof Lewin said.

For more information on the trial or to sign up to participate, email virgo-studies@unimelb.edu.au or call (03) 8344 9325.

Image credit: ©stock.adobe.com/au/pickup

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