Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis. According to the World Health Organization (WHO) around 10 million people around the world had TB in 2017 and is one of the top ten causes of death worldwide.
Reaching the WHO End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence, worldwide, by 2035, will require a new vaccine that is effective in adult individuals who have not yet been infected with Mtb, as well as in those with latent Mtb infection.
The current TB vaccine utilizes a ‘cold chain’ system to store and transport vaccines at recommended temperatures from the point of manufacture to the point of use. 75–100% of vaccines being exposed to suboptimal temperatures during dissemination. As a consequence, up to 50% of manufactured vaccines are discarded before administration. Moreover, The cold chain can also raise vaccination costs by up to 80%, further limiting the widespread distribution of safe and effective vaccines.
So scientists developed a method that prevents these crucial vaccine components from spoiling outside of a fridge - meaning vaccines will be thermally and can be reliably delivered to remote areas around the world more easily.
The technique is called ensilication which is:
“based on the solution-gelation process whereby negatively-charged silanol groups associate with charged amino acid residues through non-covalent electrostatic interactions. This results in growth of a protective silica cage around protein molecules which is subsequently vacuum-filtered and dried. The resultant silica-coated powder is capable of physically preventing thermal denaturation of the encased immobilized proteins. Subsequent chemical digestion of the silica is then used to release the protein back into solution in a native state suitable for applications such as vaccines and other therapeutic treatments.”
The antigen that the researchers targeted for improved thermal stability was the Mycobacterium tuberculosis antigen 85b (Ag85b); a leading candidate in the development of new tuberculosis (TB) vaccines. However, Ag85 alone is not sufficiently immunogenic to generate a protective immune response against M tuberculosis. However, the research group discovered that Staphylococcus aureus immunomodulator Sbi can enhance the immunogenicity of Ag85b.
Ag85b undergoes an irreversible loss of secondary structure at high temperatures and possesses a melting temperature of 73.7 °C. Researchers showed that these components were protected from heat damage when ensilicated and kept at room temperature for long periods of time without loss of structure or function.
Lead author Professor Jean van den Elsen, said: “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.”
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