Researchers working on a new tuberculosis (TB) vaccine say they have achieved a major step forward by showing that a promising TB antigen and a novel vaccine adjuvant can be protected from heat damage with a technique developed at the University of Bath.

Their method prevents these vaccine components from spoiling outside of a refrigerator, meaning a thermally stable vaccine that can be reliably delivered to remote areas around the world is more likely, the team pointed out.

There is an urgent need not only for a new TB vaccine, but also for methods to keep vaccines stable outside of the refrigeration cold chain as up to 50% of vaccine doses are discarded before use due to exposure to suboptimal temperatures. Thermostable vaccines have therefore been named a priority research area in the World Health Organisation’s Global Vaccine Action Plan 2011–2020.

The scientists published their study (“Ensilication Improves the Thermal Stability of the Tuberculosis Antigen Ag85b and an Sbi-Ag85b Vaccine Conjugate”) in Scientific Reports.

Source: University of Bath

“Ensilication, a method that encases proteins in a resistant silica cage, has been shown to physically prevent the thermal denaturation of a number of model proteins. In this study, we investigate the utility of this promising approach in improving the thermal stability of antigens and vaccine conjugates highly relevant to the development of candidate tuberculosis vaccines, including antigen 85b conjugated with the Staphylococcus aureus-protein based adjuvant Sbi,” the investigators wrote.

“Here we analyze the sensitivity of these constructs to thermal denaturation and demonstrate for the first time the benefits of ensilication in conferring these vaccine-relevant proteins with protection against temperature-induced loss of structure and function without the need for refrigeration. Our results reveal the potential of ensilication in facilitating the storage and transport of vaccines at ambient temperatures in the future and therefore in delivering life-saving vaccines globally, and in particular to remote areas of developing countries where disease rates are often highest.”

Developed at the University of Bath, ensilication shrink-wraps vaccine proteins in position using layers of silica that build up into a cage around the molecules so they don’t unravel when exposed to temperatures that would usually break them down. The proteins are held in place until ready to be removed from the silica cage and delivered.

TBA vaccine screenshot
Source: University of Bath

The research team from the departments of biology & biochemistry and chemistry first demonstrated that the TB antigen ag85b and a vaccine fused with the adjuvant protein Sbi are sensitive to breaking down outside of refrigerated temperatures. They then showed that these vaccine components were protected from heat damage when ensilicated and kept on a shelf at room temperature for long periods of time without loss of structure and function.

This is the first time that ensilication has been used to improve the thermal stability of proteins in a vaccine setting, after proof-of-principle work using model proteins, according to the researchers. The results are a big step forward not only in developing a thermally-stable TB vaccine, but in showing that ensilication could be used for many different kinds of vaccines, noted Jean van den Elsen, PhD, professor of biochemistry at the University of Bath.

“A new TB vaccine is really urgently needed to supplement or replace the existing BCG vaccine and reduce the number of TB cases and deaths, particularly as drug-resistant TB infections remain high,” he said.

vial of ensilicated protein
Asel Sartbaeva, PhD, with a vial of ensilicated protein. [University of Bath]

“Our results reveal the potential of ensilication in storing and transporting life-saving vaccines at ambient temperatures globally, in particular to remote areas of developing countries where disease rates are often highest, said Asel Sartbaeva, PhD, a lecturer in the department of chemistry and who invented the technique.

“With up to 50% of vaccines being thrown away, and refrigeration raising vaccine costs by up to 80%, this is a major global health challenge that we need to overcome. By demonstrating for the first time that ensilication works to protect vaccine-relevant proteins from breaking down outside a fridge we’re a big step closer to achieving this goal.”

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