Australian medical researchers have successfully developed a new type of vaccine targeting tuberculosis

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There is only one existing vaccine for TB and it is not effective in adults.

Researchers at the Centenary Institute and University of Sydney will next test their new vaccine in clinical trials with humans.

Australian medical researchers from the Centenary Institute and the University of Sydney have successfully developed and tested on mice a new type of vaccine targeting tuberculosis (TB), the world’s top infectious disease killer in humans.

Reported in the Journal of Medicinal Chemistry, the early-stage vaccine was shown to provide substantial protection against TB in a pre-clinical laboratory setting when tested on the rodents.

Tuberculosis is a huge world-wide health problem.

It’s caused by a bacteria that infects the lungs after it’s inhaled, is contagious and results in approximately 1.6 million deaths per year globally,” said Dr. Anneliese Ashhurst, co-lead author of the reported study and affiliated with both the Centenary Institute and the University of Sydney.

The research program targeting the deadly disease has currently taken over five years of effort to implement.

During that time Dr. Ashhurst and a team of scientists have created the advanced synthetic TB vaccine and have now demonstrated its effectiveness using mouse models.

“Two peptides [small proteins] which are normally found in tuberculosis bacteria were synthesized and then bound extremely tightly to an adjuvant [a stimulant] that was able to kick-start the immune response in the lungs,” said Dr. Ashhurst.

“We were then able to show that when this vaccine was inhaled into the lungs, it stimulated the type of T cells known to protect against TB.

Importantly, we then demonstrated that this type of vaccine could successfully protect against experimental airborne TB infection,” she said.

Professor Warwick Britton, Head of the Centenary Institute Tuberculosis Research Program and co-senior researcher on the project with Professor Richard Payne, School of Chemistry, University of Sydney, emphasized the importance of the work being done.

“There currently exists only one vaccine for TB (known as BCG) and this is only effective in reducing the risk of disease for infants,” Professor Britton said.

“It fails to prevent infection or provide long-term protection in older individuals and it isn’t considered suitable for use in individuals with an impaired immune system. More effective vaccines are urgently required to save lives,” he said.

Professor Britton is excited that the team’s vaccine strategy – directly generating immunity in the lungs – has proven to be the right research approach to take.

“The important thing is that the vaccine actually gets to the lungs because that’s where you first see TB.

Ultimately, we would love to see a form of this vaccine available for use in an easily inhaled nasal spray which would provide life-long TB protection.

Although this outcome is still many years away, we are certainly heading in the right direction.

“Our next steps will be to determine if our synthetic vaccine can be developed into a form suitable for use in humans,” said Professor Britton.

There are an estimated two billion individuals carrying TB globally and up to 10% of these individuals develop the disease in their lifetime. More than 50 percent of TB cases occur in the Asia Pacific region.

More information: Anneliese S. Ashhurst et al. Mucosal Vaccination with a Self-Adjuvanted Lipopeptide Is Immunogenic and Protective against Mycobacterium tuberculosisJournal of Medicinal Chemistry (2019). DOI: 10.1021/acs.jmedchem.9b00832

Journal information: Journal of Medicinal Chemistry
Provided by University of Sydney


The World Health Organization (WHO) provides guidance on priority targets and development pathways for vaccines against diseases of high public health interest.

The involvement of the WHO in vaccine development is driven by assessments of medical need and technical feasibility, and an absence of market incentives and sufficient funding to adequately drive the development process.

As tuberculosis (TB) kills more people globally than any other single infectious agent 1, developing a TB vaccine ranks among the highest global health priorities from a medical needs perspective.

A number of factors support the technical feasibility of a TB vaccine, including the fact that an estimated 90% of persons infected with Mycobacterium tuberculosis ( Mtb) do not progress to active disease 1, evidence suggesting that past Mtb infection provides some protection against new infections 23, and the existence of a century-old vaccine, Bacillus Calmette-Guérin (BCG), that provides partial protection in children which may, under some circumstances, extend for decades 4.

The current imperative is to improve our understanding of the type of immunological responses needed to provide robust protection against Mtb infection or TB disease, and to use this information to efficiently develop new, safe and effective TB vaccines.

In response to the compelling public health need for a TB vaccine, in October 2017 the WHO convened experts and representatives of important stakeholder institutions involved in vaccine development to assist the WHO in a two-pronged effort to accelerate TB vaccine development.

The first effort was dedicated to defining a preferred product characteristics (PPC) guidance document for new TB vaccines, now publicly available 5.

The second was to convene a meeting providing an opportunity for the exchange of cutting-edge information relevant to TB vaccine development, from basic science to later stage research. The proceedings of this meeting are summarized in this document.

b. The WHO Global TB Programme

Each year, the WHO publishes the Global Tuberculosis Report, documenting the overall status of the global TB epidemic. The 2017 version of this report highlights the following statistics for the state of the TB epidemic in 2016 1:

  • 1,674,000 TB deaths, of which 374,000 were in HIV co-infected persons (“the ninth leading cause of death worldwide and the leading cause from a single infectious agent, ranking above HIV/AIDS” 1); 374,000 of these deaths occurring in HIV-infected persons
  • 10.4 million cases of TB disease, 56% of which were in 5 countries: India, Indonesia, China, the Philippines and Pakistan;
  • 600,000 cases of rifampicin-resistant TB (RR-TB), of which 490,000 were multidrug-resistant TB (MDR-TB). Globally, an estimated 4.1% of new cases and 19% of previously treated cases had MDR or RR-TB, with 47% of the global total of drug-resistant cases reported from China, India and the Russian Federation. 250,000 of these 490,000 died.
  • A U.S. $2.3 billion funding gap for financing TB care and prevention existed in 2017

The WHO strategy to tackle the global epidemic of TB was set forth in the WHO End TB Strategy, endorsed by the WHO General Assembly in 2014 6.

The End TB Strategy relies on a number of priorities in the global response to the TB epidemic. These priorities include improving approaches to identifying cases of TB, addressing MDR-TB as a true public health crisis, and accelerating strategies to better prevent, identify and treat TB in HIV-infected individuals.

A three-pillared approach to the TB epidemic is being implemented:

1) to advocate for integrated, patient-centered TB care and prevention;

2) to support the creation of bold policies and supportive systems to curb the spread of TB; and

3) to support intensive research and innovation to create the new tools needed to prevent and treat control TB, including better diagnostics and drugs, and a new vaccine capable of preventing TB disease.

A key objective of the WHO End TB Strategy is a 90% reduction in TB incidence, from the 2015 annual incidence of greater than 100 cases per 100,000 population to less than 10 cases per 100,000 persons by 2035 6.

Currently, the annual decline in TB incidence is not nearly fast enough to meet the expressed goals 1.

As evidenced by the successes of the social protections provided under the Marshall Plan in the aftermath of World War II, a 10% rate of decline could be considered feasible through optimization of currently available social and medical interventions, although this is a major proposition in and of itself which would require a heightened degree of global commitment to achieve. Without the development of new TB prevention modalities, however, this rate would be expected to flatten out to a 5% decline per year by 2025, again, not nearly sufficient to meet the End TB Strategy 2035 goals 6.

Only the introduction of new tools, including better point-of-care diagnostics capable of quickly and reliably diagnosing TB, including cases of drug-resistant (DR) TB; better drugs for treating drug-sensitive and DR-TB over a shorter period of time than is currently required; and, most importantly, a new vaccine capable of preventing TB disease, introduced by 2025, would result in an acceleration to the 17% per year decline of TB incidence necessary to meet the 2035 goals6.

Currently, a U.S. $2.3 billion annual research gap exists in efforts to develop new tools to control TB, including better diagnostics and drugs, as well as TB vaccines 1 a figure that may represent a conservative estimate of the actual funding shortfall, particularly considering the need to invest in efforts that will result in the development of an effective vaccine by 2025 for the targets to be reached.

The ongoing United Nations (UN)–led efforts to prioritize action against TB is illustrated by a series of high-level political meetings. Top-level political engagement was demonstrated in Russia in November 2017 at the gathering of 194 ministers of health, research and finance, alongside the WHO Director General and the President of the UN General Assembly. This was followed by an interactive civil society meeting, attended by more than 250 representatives from civil society, academia, NGOs, and the private sector, setting the stage for the first ever UN General Assembly high level meeting (HLM) on TB in New York in September 2018.

The HLM aims to deliver an ambitious political declaration on TB endorsed by Heads of State, which will strengthen action and investments to end TB. Issues to be discussed include the increase in drug-resistant TB strains, the need to provide adequate resources to control the epidemic, and to create a universal monitoring program to track the epidemic and the world’s response to it, will be highlighted. Accelerating development of a vaccine for TB will be a critical component in the future of TB prevention and care, therefore urgently requires increased resource allocation and political support in upcoming years.

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