Overview of MHF and Precision Vaccines Program Partnership
Given the heavy burden of global TB and the newfound promise in translational vaccinology, the Precision Vaccines Program (PVP) at Boston Children’s Hospital, directed by Dr. Ofer Levy, has engaged in a partnership with The Mueller Health Foundation to reduce the burden of tuberculosis (TB) via immunization. The Mueller Health Foundation will partner with the PVP in three inter-related projects: 1) Establish a working group to advance and implement an optimal Bacille Calmette-Guérin (BCG) vaccine; 2) discovery of a novel adjuvanted tuberculosis vaccine and 3) create educational videos to communicate and raise awareness of the importance of TB vaccines and treatment options. The three main aims of the collaboration are outlined in greater detail below.
Aims of the Collaboration
Aim 1: Establish a Working Group to Advance and Implement an Optimal BCG Vaccine
PVP will apply human in vitro modeling of BCG responses, systems biology approaches such as metabolomics as well as analysis of clinical trial results to:
- Convene a BCG administrative working group to include experts in vaccinology, immunology, infectious diseases, from both within and outside of the PVP. This group will conduct a landscape analysis and generate the data and engage the key stakeholders and decision makers to move forward an optimal BCG plan;
- Assist the Mueller Foundation in a supportive role with TB conference planning & implementation;
- Determine which of the licensed BCG vaccine provides optimal vaccine-specific protection against TB and non-specific heterologous protection against off-target respiratory infections (e.g., influenza and SARS-CoV-2);
- Define biomarkers of BCG immunogenicity and protection to guide selection of optimal BCG vaccines and inform development of novel TB vaccines; and
- Inform design of a clinical trial to compare BCG formulations in vivo.
Aim 2: Discovery of a Novel Adjuvanted TB Vaccine
PVP will employ cutting edge techniques to develop a novel adjuvanted TB vaccine that would be amenable to much more precise formulation and production and could eventually replace BCG. PVP will:
- Perform in silico analysis of TB genes expressed in hypoxic granulomas to identify candidate antigens;
- Define immunogenic epitopes in silico;
- Conduct a screen of small molecule adjuvants active towards human newborns and adults as benchmarked to BCG to determine which is optimal to enhance both specific (vs TB) and heterologous (broad innate immune memory) responses to a novel lead TB vaccinal antigen in vitro (human) and in vivo (mice); and
- Synthetically mimic the release kinetics of BCG for sustained immunostimulation in an in vivo neonatal mouse vaccination/challenge model
Aim 3: Create Video Documentary
PVP will partner with documentary film maker Joe Winston (Ow My Eye Productions; Chicago, IL) to develop and disseminate optimized content conveying the importance of vaccines to a lay audience. The PVP and MHF partnership will develop a series of modular educational films aimed at high school and college students.
About The Precision Vaccines Program (PVP)
Established at Boston Children’s Hospital in 2016, the Precision Vaccines Program (PVP) fosters international collaboration among academia, government and industry to employ advanced technologies to discover and develop vaccines tailored to protect vulnerable populations such as the very young and the elderly. Program members have domain expertise in vaccinology, clinical trials, immunology, molecular biology, administration, data management, biostatistics, bioinformatics, and systems biology. The PVP has developed a multi-disciplinary team to advance vaccine development, including (a) development of human in vitro models to accelerate and de-risk targeted vaccine development, b) use of systems biology including proteomics and metabolomics, (c) a robust Data Management Core implementing data security, quality control, quality assurance and integration, and (d) development of local and collaborative social media and documentary to disseminate findings to the lay public. For more information regarding the PVP, please visit:
Link to Dr. Ofer Levy’s TED talk re Precision Vaccines: