Research Spotlight: Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model

Posted on October 22, 2021

Tb Research Susan Baldwin Spotlight

Globally, tuberculosis, a treatable and preventable disease, kills 1.6 million people every year. A latent form of tuberculosis, Mycobacterium tuberculosis (Mtb), is estimated to infect nearly a quarter of the world’s total population. It is imperative that we as a scientific community find alternatives to the current TB vaccines being used today. Keep reading to learn more about a research team doing just that!

Why do we need to investigate more TB vaccines if the current vaccine is working?

Drug-resistant TB is becoming more and more of a threat. But aside from this, there are other issues associated with having only the currently approved vaccine for the treatment and prevention of TB. Some of these issues are the cost of the current goods used in the vaccine, supply chain related to the goods used in the vaccine, and possible improvement of the vaccine’s efficacy against latent Mtb. If there are more options of viable treatments for TB, we have a better chance of being able to make and provide these treatments to a larger portion of the population.

Current Efforts to Develop A New Vaccine for TB at Seattle Children’s Research Institute

Recent vaccine prevention of disease trials (POD) have given much hope to subunit vaccines and their utilization in the treatment and prevention of TB. Subunit vaccines differ from traditional vaccines in that only one or a few components of the original pathogen, called antigens, are used in the vaccine. These antigens are highly purified or synthetic and are considered much safer than whole-pathogen vaccines. The use of subunit vaccines has been challenging due to their weakness and lower stability compared to whole-pathogen vaccines. So, antigens alone are not capable of producing the desired immunogenicity to a pathogen – how can we increase the immune response generated by a subunit vaccine? In one word, adjuvants.

Dr. Susan Baldwin and the Coler Research Group from the Seattle Children’s Research Institute partnered with the Infectious Disease Research Institute and the Department of Global Health of the University of Washington to investigate the use of a liposomal adjuvanted antigen formulation in the preventative treatment of TB. The adjuvant used for this study was Avanti’s GLA (Monophosphoryl Lipid A (synthetic) (PHAD)).

The full formulation consisted of four Mtb proteins, GLA, and QS-21 formed into aqueous nanosuspensions, stable emulsions, or one of three types of liposomes. The liposomal carriers used for this study were PEGylated (DPPC:DSPE-PEG2000:cholesterol), anionic (DPPC:DPPG:cholesterol), and neutral (DOPC:cholesterol).

The formulations were tested in mice and the results showed that the anionic and PEGylated liposomal formulations did not elicit a great immune response. However, GLA - stable emulsions and GLA - neutral liposomes containing QS-21 elicited a high cellular and humoral immune response and protected mice against Mtb. The data gathered from this study combined with other studies and trials being conducted for TB vaccines provide invaluable information that could reduce the cost and timeline for highly effective TB vaccine candidates.

To read the full research article follow the link, click HERE!

And, don't forget to check out our Interview with Dr. Susan Baldwin!

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