December 6, 2023

The moment is now: navigating the path to TB vaccine success at the Union Conference and beyond

This year’s Union Conference set the scene for what could be the biggest year to date for tuberculosis (TB) vaccines.

Union 2023We joined thousands of researchers, advocates, and global health experts in Paris in November for the first in-person Union World Conference on Lung Health since 2019. This year’s Union Conference provided the first major in-person gathering for the global TB community since the United Nations High Level Meeting (HLM) on TB in September. With the commitments endorsed by member states still fresh in our collective psyche, delegates were doubly focused on what we must now do to translate member state commitments into action.

The week was also framed around the recently released WHO 2023 Global Tuberculosis Report. In 2022, 7.5 million people were diagnosed with TB — the highest number since global monitoring began in 1995 — and the number of people estimated to fall ill with TB stayed steady at 10.6 million. The gap between those who fell ill with TB and those who were diagnosed, while still large, was reduced by 900,000 people in 2022 and has returned to the pre-pandemic level of 2019. Further, 1.3 million people died from TB in 2022, down from 1.6 million in 2021. Drug-resistant TB remains a priority ahead of next year’s HLM on antimicrobial resistance. Of an estimated 410,000 people who developed drug-resistant TB in 2022, only about 40% accessed treatment.

While these findings signal the start of a recovery in the global TB response following damaging COVID-19-related setbacks, we urgently need new TB vaccines, diagnostics, and drugs if we stand a chance of meeting the End TB goals by 2030. Vaccines remain the key missing puzzle piece. Now, new TB vaccines may finally be within reach more than a hundred years since the first and only TB vaccine, bacille Calmette-Guérin (BCG), was introduced. Getting there this decade, however, will require dramatic funding increases.

The last year has provided real momentum to realize this goal. A range of efforts are underway across the field, from preclinical development to clinical trials to policymaking and country preparedness. We heard from experts at sessions throughout the conference about this work and what more must be done to make new TB vaccines a reality.

The promise of the pipeline

With 17 TB vaccine candidates in clinical development and multiple candidates in late-stage efficacy testing, there is genuine optimism that the pipeline may soon (i.e., this decade) bear fruit. Several late-stage efficacy trials are on the verge of commencing in 2024, including the Phase III clinical trial of M72/AS01E and a Phase IIb trial of MTBVAC in adolescents and adults. Results presented at the Union Conference on the Phase II of M72/AS01E in people living with HIV (PLWHIV) demonstrated a favorable safety profile and support the inclusion of PLWHIV in the planned Phase III trial.

But the first TB vaccine across the line won’t be a catch-all solution. We need to support the efficacy testing of other promising candidates in late-stage clinical trials and develop next-generation candidates that are more effective, easier to administer, and work for all forms of TB, in all populations. At present, the pipeline is an ‘inverted pyramid’, with more candidates in late-stage than early development. We need to flip this on its head and bring diverse candidates into the pipeline based on new strategies, antigens, and platforms to ensure better and more effective candidates reach the last mile.

Work on next-generation candidates is advancing, including two mRNA vaccine candidates from BioNTech, which entered Phase I testing this year. In the preclinical space, researchers shared updates on the development of new BCG formulations, such as a dry powder inhaled BCG vaccine tested in a guinea-pig model and a modified BCG vaccine candidate to induce enhanced protection against TB in mice. Elsewhere, new epitopes are under investigation in in vitro studies to inform a new multi-epitope TB vaccine.

Vaccines don’t save lives, vaccination saves lives

To quote a recent correspondence in Nature, “A vaccine cannot deliver on its potential unless it reaches those who need it, when they need it.” Ensuring access is an endeavor that must begin years in advance of market entry. The foundations for country implementation are already being laid. Speakers at an IAVI-coordinated symposium on the need for coordinated action to accelerate access and a Community Connect session from SMART4TB highlighted a range of efforts underway. These include country-level demand forecasts, complementary efforts to identify gaps in country readiness from SMART4TB and the WHO, and forthcoming policy frameworks from the WHO on evidence considerations for vaccine policy and a Global Framework to Prepare for Country Introduction.

IAVI, FIND, and TB Alliance were joined by Nandita Venkatesan, a TB survivor and activist, for a Community Connect panel on the final day of the conference, where a discussion on gaps in TB research explored the potential implications for access to new TB tools. The need for further research on the role of subclinical TB in TB transmission was one such gap discussed. Panelists also echoed the demands of members of the Global TB Community Advisory Board in an earlier symposium, calling for the inclusion of key groups in TB vaccine research who have been historically left out of clinical trials, including people successfully treated for TB and pregnant women and people of other gender identities.

The full participation of communities across the research-to-implementation continuum will be critical to develop TB tools that meet the needs of those who seek to benefit most. This is a role that extends to accountability, as emphasized by Venkatesan who said, “Even if we serve on community boards of organizations, that doesn’t mean we hold back in holding them accountable.”

Deeds not words!

The last 12 months have in principle been a banner year for TB vaccine funding, dominated by the $550 million investment from the Bill & Melinda Gates Foundation and Wellcome to conduct the Phase III trial of M72/AS01E. This funding represents almost five times what the world spends on TB vaccine development in any given year. While it’s laudable that two of the world’s largest charities stepped up to fund M72/AS01E, developing vaccines against the world’s deadliest infectious disease should not be left to the charity sector.

TB vaccine stakeholders redoubled their calls throughout the week for increased public sector funding for TB vaccine development. Advocates are taking a solutions-oriented approach, illustrating how and where member states can deliver joint investments. During the TB Vaccine Advocacy Roadmap (TB Vax ARM) Community Connect panel on resource mobilization, panelists urged governments and other funders to step up and invest their fair share in TB R&D, including by leveraging in-country research, regulatory, and manufacturing infrastructure. Read this T20 policy brief from the TB Vax ARM for more detail.

The role of middle-income high-burden countries was explored in a symposium on sustainable models for TB vaccine development and delivery in BRICS countries. Insights were shared on how to strengthen country-level ownership, such as through domestic investments in the research agenda and supporting local vaccine manufacturing and distribution.

New champions, like Brazil, are also stepping to the fore. Brazil assumed the 2024 G20 presidency on December 1, 2023, and will preside over the G20 during a year that the Africa Union is for the first time a permanent member, representing the interests of its almost 1.4 billion residents. Brazil is also co-chairing the WHO TB Vaccine Accelerator Council alongside Indonesia and will host the 7th Global Forum on TB Vaccines in Rio de Janeiro this coming October.

What’s next?

The Union Conference set the scene for what could be the biggest year to date for TB vaccines. It really is now a matter of when, not if, we get new TB vaccines. And as Lord Nick Herbert, chair of the Global TB Caucus, said during the opening ceremony, “Securing these resources will require political leadership in every country… This isn’t a medical or scientific challenge, it’s a political challenge. Tell them that no pandemic has been ended without an effective vaccine, and we don’t have one.”