New method of rapid vaccine development for preclinical testing

Scientists have developed a method for the rapid synthesis of safe vaccines, an approach that could be used to test vaccine strategies against new pandemic pathogens such as SARS-CoV-2, the virus that causes COVID-19. The study was conducted at the University of Sydney, Australia.

The team demonstrated the application of this method with a new vaccine against tuberculosis, which generated a powerful protective immune response in mice. The only current vaccine against tuberculosis, the Bacille Calmette-Guérin vaccine, uses live bacteria that are injected. It is effective in infants but has reduced effectiveness in adolescents and adults and poses significant health risks for immunocompromised patients, especially for people living with HIV / AIDS.

Protein vaccines have been shown to be very safe, but they have to be mixed with activators or adjuvants to make them effective, which is not easy.

“The challenge is to make sure that our immune cells see the protein and the adjuvant simultaneously. To overcome this difficulty, for the first time, we have developed a method which synthesizes the protein with an attached adjuvant as a single molecule, ”said lead co-author Dr Anneliese Ashhurst.

A major hurdle overcome by scientists has been the difficulty of fusing hydrophobic adjuvants with a water-soluble protein antigen.

“We got around this problem of keeping the hydrophobic and hydrophilic molecules together in a vaccine by developing a way to permanently bind the protein and adjuvant together into a single molecule using synthetic chemistry. Our approach overcomes solubility problems encountered by other methods, ”said Professor Richard Payne, one of the principal investigators.

The team claims that the synthesis of a whole bacterial protein with an attached adjuvant has not been done before.

According to the researchers, the other major advantage of this method is that vaccines for a range of diseases can be developed quickly and safely in the laboratory.

“We don’t need to grow the actual pathogen in the lab to make the vaccine,” Dr Ashhurst said. “With this new method, we can quickly and safely synthesize very pure vaccines in the laboratory and integrate them directly into animal models for preclinical testing.”

The results are published in PNAS.