University of Oxford - Testing new ways to fight TB: Challenge trials
The video highlights the urgent need for a TB vaccine, given its high mortality rate compared to other pathogens. Unlike diseases with significant funding, TB lacks financial backing despite its global impact. The discussion introduces a novel approach using a controlled human infection model, where volunteers are deliberately infected with a surrogate like BCG instead of TB. This method helps test the efficacy of vaccines by observing if vaccinated individuals clear the BCG infection faster, indicating a protective effect. The video also contrasts the complexity of developing a TB vaccine with the relatively straightforward process for COVID-19, due to TB's 4000 proteins compared to COVID-19's single target protein. This complexity, coupled with the high cost and large scale of traditional trials, makes the controlled human infection model a promising alternative for prioritizing vaccine candidates for further trials.
Key Points:
- TB kills more people than any other pathogen but lacks significant funding.
- A controlled human infection model uses BCG as a surrogate to test vaccine efficacy.
- Volunteers are monitored to see if vaccinated individuals clear BCG faster, indicating protection.
- TB vaccine development is complex due to 4000 proteins, unlike COVID-19's single protein target.
- Human challenge models can help prioritize vaccine candidates for costly phase three trials.
Details:
1. 🦠 The Global Threat of TB
- Tuberculosis (TB) is the leading cause of death by an infectious disease, surpassing others despite low industry investment.
- In 2021, TB caused an estimated 1.6 million deaths worldwide, highlighting its severe impact.
- Approximately 10 million people fell ill with TB in 2021, demonstrating its widespread reach.
- The disease disproportionately affects low and middle-income countries, exacerbating existing health inequalities.
- Efforts to combat TB face significant challenges due to drug resistance and lack of new treatments.
2. 🌍 Collaborative Vaccine Development
- Developing vaccines requires a global community approach to effectively address pathogens that impact multiple regions.
- Collaborative efforts can leverage diverse expertise and resources, leading to more efficient vaccine development processes.
- International collaborations can help in sharing data, distributing resources equitably, and ensuring faster response times to emerging health threats.
- An example of successful collaboration is the rapid development of COVID-19 vaccines through partnerships across countries and organizations.
3. 🧪 Innovative Human Infection Models
3.1. Controlled Human Infection Models
3.2. Use of BCG as a Surrogate Pathogen
4. 🔬 Inside the Vaccine Trial Process
- Vaccine trials are structured into phases, beginning with small-scale safety assessments and progressing to larger efficacy trials.
- Participants are randomly divided into two groups: one receiving the vaccine and the other a placebo, ensuring a controlled comparison of outcomes.
- The trial uses BCG administration to measure how quickly vaccinated individuals clear the infection, indicating the vaccine's protective effect.
- Success is defined by vaccinated participants demonstrating a faster clearance of BCG compared to the control group, highlighting the vaccine's efficacy.
- This structure allows researchers to assess both the safety and effectiveness of the vaccine through a rigorous, phased approach.
5. 👩🔬 The Volunteer Perspective
- A volunteer participates in a TB trial, undergoing a bronchoscopy to assess the immune response to an aerosolised vaccine administered two weeks earlier.
- The volunteer expresses pride in contributing to research that could benefit individuals suffering from tuberculosis, highlighting the trial's potential impact on public health.
- The trial aims to evaluate the effectiveness of new TB vaccines, with volunteers playing a crucial role in advancing medical research.
6. 🧬 Overcoming Vaccine Development Challenges
- Covid-19 was relatively easy to target with a vaccine because it involves one protein, whereas TB involves 4000 proteins, making vaccine development more complex.
- TB vaccine trials are especially challenging due to the need for large-scale trials involving 20,000 subjects, costing around half a billion dollars, limiting the number of studies that can be conducted.
- Human challenge models could allow for the testing of multiple vaccines to identify the most promising candidates, which can then be prioritized for phase three trials.