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20 Aug 2020

Vaccine research pipeline flourishes

Six vaccine strategies in development at the Doherty Institute are driving the search for solutions to some of the world’s nastiest infectious diseases.

Vaccination is arguably one of history’s greatest inventions. Vaccines eradicated smallpox globally and have significantly reduced many other infectious diseases.

Yet, vaccines remain elusive for many high-impact diseases such as malaria and HIV. Researchers across the Doherty Institute are at varying stages of creating vaccine strategies for a number of infectious diseases.

Two vaccine strategies against malaria

University of Melbourne is investigating two paths for the development of a vaccine for malaria.

Professor Heath’s team discovered that memory immune cells residing in the liver were more efficient against liver stage malaria parasites than memory cells circulating in the blood.

Based on this finding, they developed a ‘prime and trap’ vaccine method involving two injections.

The ‘priming’ injection sets the immune response in motion, boosting the army of immune cells against malaria and helping to attract those cells to the liver. The ‘trapping’ injection captures an abundance of these immune cells in the liver and then converts them into liver resident immune cells that permanently guard the liver from malaria infection.

“Since this work was published in 2016, we’ve tested this method on real molecules associated with malaria (known as antigens) and we’ve identified a novel malaria antigen that is highly protective,” says Professor Heath.

“However, ‘prime and trap’ is a complex vaccine that has three components and requires two separate injections, making real world use difficult. We’ve worked hard to simplify the vaccine; now all components can be injected at the same time.”

The second strategy is a simpler vaccine that also generates the required immune cell response but comprises a single molecule containing all the critical components. This approach is patented and is a collaboration with University of Melbourne Professor Dale Godfrey and researchers from Victoria University in New Zealand and Avalia Immunotherapies.

A vaccine platform against Zika virus

University of Melbourne Professor Jason Mackenzie and his team investigate viruses such as dengue and the newly emerging Zika virus. The mosquito-borne illness can cause microcephaly and other congenital malformations in children of mothers who contracted the virus during pregnancy.

“Our research on dengue and Zika virus has shown us that these viruses use human proteins to replicate efficiently and they can change the fats of the host cell, which can induce inflammation,” explains Professor Mackenzie.

To advance treatment options against these diseases, they have constructed a vaccine platform against Zika virus. It is extremely effective in producing specific antibodies that recognise the virus and neutralise its ability to infect cells. The team is working with other colleagues at the Doherty Institute to advance these developments further and to move the vaccine into clinical trials.

Antibodies from cows could be the key to an HIV vaccine

University of Melbourne Professor Damian Purcell and his team are working on a vaccine for HIV – using cows.

“We think that cows have a genetic advantage and make special antibodies against tricky viruses,” explains Professor Purcell.

“The HIV virus has a spike on its envelope, which it uses to enter cells. It is shrouded in protective sugars.

“The cow antibodies can more easily reach through these sugars and bind tightly to important underlying protein structures, which enables the antibody to be effective against a wide range of HIV strains.”

Professor Purcell says that some of the antibodies they have made from the cow have been remarkably potent.

“If we could achieve the same results in humans then we would be closer to an effective HIV vaccine.”

Research needs to target virus-infected cells as well as free virus particles

University of Melbourne Professor Stephen Kent and his team made an important discovery when studying how broadly neutralising antibodies prevent transmission of simian immunodeficiency virus (SIV) – an HIV-like virus that infects monkeys.

“During sexual transmission of HIV, virus is present in the form of the seminal plasma that can either be free virus or virus-infected cells,” explains Professor Kent.

Professor Kent and his team administered macaque models with virus-infected cells followed by broadly neutralising antibodies and found that in many cases they couldn’t protect against the cell-associated virus.

“Virus-infected cells are not visible to any immune intervention you might use. You could have the most potent microbicide that stops sexual transmission of the free virus, but if the cells get across, you’re still going to get infected.”

Nanoparticles to boost the immune response

Professor Kent is also a Chief Investigator for the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology. In collaboration with University of Melbourne Professor Frank Caruso, Professor Kent and his team are investigating the use of nanoparticles as vaccine-delivery tools.

“Particles with a wide range of properties – size, charge and material – can be fabricated, and each will interact with cells of the immune system in a different way,” explains Professor Kent.

“We’re trying to determine which nanoparticle properties will elicit the desired immune responses, and we’re using imaging to see how these particles affect vaccine responses in vivo.”

This article was first published in the Celebrating five years of the Doherty Institute Impact Report.