New Method Tests Vaccine Strategies Against Novel Pathogens

by Angela Mohan on Jan 19 2021 11:00 AM

New Method Tests Vaccine Strategies Against Novel Pathogens
Protein-based immunization method developed by the Australian researchers, can be used to test various vaccine strategies against novel pandemic pathogens including SARS-CoV-2.
The research was led by Professor Richard Payne at the University of Sydney and Professor Warwick Britton at the Centenary Institute. The team has demonstrated application of the method with a new vaccine for use against tuberculosis (TB), which has generated a powerful protective immune response in mice.

Researchers want to identify vaccine strategy to assist in the rapid pre-clinical testing of new vaccines, particularly for respiratory illnesses.

"Tuberculosis infects 10 million and kills more than 1.4 million people every year," said joint first author Dr Anneliese Ashhurst from the University of Sydney.

"Historically, it is the leading cause of death worldwide from a single infectious agent. So far, a TB vaccine that is highly effective and safe to use in all populations has eluded medical science."

BCG is the only current vaccine for tuberculosis that uses an injected live bacterium. It is effective in infants but has low effectiveness in adolescents and adults and poses significant health risks for immunocompromised patients, including patients with HIV/AIDS.

Dr Ashhurst said: "The challenge is to ensure that our immune cells see both the protein and adjuvant simultaneously. To overcome this difficulty, for the first time we have developed a method that synthesizes the protein with an attached adjuvant as a single molecule."

The vaccine strategy and synthetic technology could be deployed to rapidly develop new vaccines for pre-clinical testing, the researchers say, including the respiratory pathogen that causes COVID-19. Their results are published in the Proceedings of the National Academy of Sciences of the United States of America.

Vaccines should stimulate behavior in protective T-cells that allows them to recognize the pathogen as an antigen, or foreign body. In the case of tuberculosis, our immune system needs to respond quickly to the bacteria that causes TB - Mycobacterium tuberculosis - to reduce infection in lungs.

Inhaled vaccine provides a low-dose immune-stimulating molecule with a bacterial protein attached directly to an adjuvant.

A major hurdle overcome by the scientists was the difficulty in fusing hydrophobic (water-repellent) adjuvants with a water-soluble protein antigen.

"We got around this problem of keeping hydrophobic and hydrophilic molecules together in a vaccine by developing a way to permanently bind the protein and adjuvant together as a single molecule using synthetic chemistry.

Our approach overcomes the solubility problems faced by other methods," said Professor Payne from the School of Chemistry and Deputy Director of the ARC Centre for Innovations in Peptide & Protein Science (CIPPS).

Professor Britton from the Tuberculosis Research Program at the Centenary Institute said: "As well as providing a rapid method to develop a range of vaccines for pre-clinical testing, we expect that this pulmonary vaccination approach will be particularly beneficial for protecting against respiratory diseases."

He said: "We hope that an inhaled vaccine for tuberculosis using a protein-based immunization will allow us to develop a universal and safe approach to combatting this deadly disease." and they can be developed rapidly and safely in the laboratory.

"We don't need to grow the actual pathogen in the lab to make the vaccine," said Dr Ashhurst, who holds a joint position in the School of Chemistry and the School of Medical Sciences.

"Using this new method, we can rapidly and safely synthesise highly pure vaccines in the lab and take them straight into animal models for pre-clinical testing."