David Lewinsohn
Working Group on New TB Vaccines

Developing a TB vaccine takes many years and carries a high risk of failure. There are challenges that we need to overcome to increase the likelihood of success.

Developing TB vaccines is especially challenging compared to other diseases. One reason is the TB bacteria can hide inside immune cells where they are protected against a broad variety of immune
responses. This means we have to develop vaccines that can kill or control TB bacteria despite its ability to hide inside some immune cells.

Another challenge is that no animal models used in the preclinical stage of development, before testing in humans, have yet been demonstrated to predict vaccine efficacy. Specifically, we do not have animal models that reflect important clinical outcomes such as
remaining healthy once infected. Developing fit-for-purpose animal models, models that more accurately reflect how TB progresses in humans, would better predict how effective a vaccine would
be prior to entering human trials, allowing for a greater chance of success.

Another challenge is ensuring that new TB vaccine candidates are being developed and are progressing through the stages of research.

A related challenge is to ensure that there is diversity in the types of TB vaccine candidates being explored in the TB vaccine pipeline. Many of the vaccine candidates in the TB vaccine pipeline use the same platform and include similar antigens, each attempting to trigger similar immune responses.

It's important to note that most vaccine candidates that are in development will fail testing at some point. It's likely that we'll need more than one TB vaccine approved for use in different populations and with different indications. What this means is that we need to get more TB vaccine candidates into clinical development.

Achieving this will require investment in laboratory capacity and infrastructure, and more funding to support the work of researchers currently involved in TB vaccine research and importantly to
encourage and support young scientists to engage in TB vaccine research.

We do not yet have what is known as a correlate of protection against TB. A correlate of protection refers to the specific type or types of immune responses and the levels of these responses that
need to be stimulated in order to achieve protection against TB infection or TB disease.

Identifying a correlate of protection would give TB vaccine developers a way to predict how well a vaccine candidate might work, making the research process more efficient
and far less costly.

There are some solutions for speeding up vaccine trials while not cutting any corners when it comes to safety, and with additional funding these approaches could be feasible to carry out.

One way to do this would be to invest in conducting clinical trials in parallel, potentially overlapping different phases of clinical trials and clinical trials in different populations.

Another would be to streamline the design and reduce the length of efficacy trials while still meeting regulatory requirements for licensure.

Another would be to reduce the lag time between different phases of trials. This could be done by ensuring that funding and resources are available to advance multiple promising vaccine candidates
through each stage or phase of development without delay.

We need more trial sites, particularly in places with a high burden where the need for new TB vaccines is greatest. We need to be able to conduct vaccine trials in different regions, working with different populations. To be able to conduct multiple large-scale trials at the same time will require a significant investment in increasing the number and capacity of clinical trial sites.

Committing to actually manufacturing new vaccines once we have a strong indication that they are safe and effective is essential to making them available quickly once the regulatory authorities
approved them. Sometimes it becomes clear the vaccines are safe and effective during late stages of research. So if manufacturers start preparing to produce vaccines at that time, it can cut the lag
time between when a vaccine is approved and when it becomes available to the public.

The key takeaway is that the research community knows what we need to successfully develop new TB vaccines. If researchers have the resources and the coordination, we could accelerate the development of new TB vaccines.