The long road to a leprosy vaccine

Where are we now in developing LepVax, and what work is left to do?

The long road to a leprosy vaccine

Why has LepVax — the name for the leprosy vaccine — taken decades to develop, while an effective Covid-19 vaccine took less than a year to create?

In May, The Leprosy Mission and Hope Rises International co-hosted a webinar to give an update on LepVax's development, and how far we have left to go.

Dr Paul Saunderson, former Medical Director at Hope Rises International and retired clinician with ample experience in leprosy and NTDs, walked through the lengthy timeline leading up to this point. Multi Drug therapy (MDT) revolutionised leprosy treatment in 1981, and the discovery of the human and M. leprae genomes made the reality of a vaccine closer within reach. 25 year later, though, we still don't have a vaccine.

Saunderson attributed LepVax's slow development to a few causes: bacillus, the bacteria that grows leprosy, is a slow-developing bacteria, so trials take longer. Additionally, as is implied with the designation “neglected,” there is less political pressure, and thus less funding, for a vaccine.

Nonetheless, scientists, policymakers, donors and project managers are working to bring a finished vaccine to communities in need.

MDT treats leprosy, but treatment has not ended transmission

Covid's strengths: political pressure and sufficient funding

Leprosy's challenges: slow-growing bacillus, slow trials, lower funding & political urgency

How LepVax works: Making the science accessible

Dr Veronica Schmitz Pereira walked through the science behind LepVax, explaining how the vaccine will contribute to the goal of zero leprosy by working in both post-exposure and pre-exposure instances. For persons already affected by leprosy, the vaccine will prevent further damage and development, and for individuals who have not been exposed, the vaccine will prevent leprosy from ever developing.

“LepVax works like fight training. The vaccine shows your body what the enemy looks like, so it knows how to fight when the enemy really appears.”

1. The vaccine is applied	It contains harmless pieces of bacteria, and it does not cause the disease.
2. The body learns	The immune system recognises these pieces, creating a “memory” of defense.
3. The defense is activated	Defense cells (T lymphocytes) learn to attack the real bacteria.
4. Guaranteed protection	If the bacteria appear, the body already knows how to fight it — before and after contact.

What makes LepVax different

For those familiar with the development of the leprosy vaccine, Pereira explained how LepVax is distinct from the BCG vaccine. The BCG vaccine was primarily developed for tuberculosis, but it also offers some level of protection against leprosy. Studies have shown BCG's overall protective effect in preventing leprosy is just 26 percent, which is a far cry from full protection.

LepVax, in constrast to BCG, will offer full protection against leprosy, as it is designed specifically to prevent leprosy development. The vaccine is composed of LEP-F1 — a fusion of four leprosy antigens — that have proven acceptable and safe when administered in 21 healthy adults.

For preclinical evidence, researchers found the antigen reduced the M. leprae bacterial burden in the mouse model, and LepVax showed a safer nerve protection profile than BCG.

As for the goals of LepVax, the vaccine will reduce not only leprosy diagnoses, but it will also reduce nerve damage and cases of relapse, and it will enhance the wellbeing of those treated with the vaccine.

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The science exists. The next challenge is creating the conditions to translate this science into impact for patients and communities affected by leprosy.

Dr Veronica Schmitz Pereira

Two goals, one vaccine

Prevent new cases

Dr Becky Rivoire, LepVax Program Coordinator for Hope Rises International, expanded upon LepVax's ability to both prevent new cases and reduce impairment — something neither BCG nor MDT can accomplish. As for preventing new cases, LepVax will stop transmission by vaccinating close contacts and people in endemic communities before they become infected.

She clarified how this prevention will not require any new infrastructure: LepVax is administered as a simple injection, the same technique as childhood vaccines, and it has a low cost for scalable manufacturing. Last, LepVax is stable to be shipped alongside other medicines, and researchers are working towards stability at ambient temperatures. With newer drugs and PEP constantly getting better, LepVax could work alongside these to provide lasting immunity.

Reduce impairment

As for the second goal of LepVax — reducing impairment — the vaccine will help people already being treated for leprosy to improve their outlook and quality of life. In animal studies, LepVax delayed nerve damage, which is a major cause of disability. In this way, LepVax could serve as a therapeutic alongside MDT to improve the lifestyle and wellbeing of persons affected by leprosy. Rivoire explained that this therapeutic purpose will be tested in future trials.

What researchers know, and what we still need to prove

What we know

LepVax prevents infection by blocking M. leprae
LepVax reduces nerve damage, delaying impairment (in animal models)
LepVax is safe to use in people, as demonstrated in Phase 1a

What we need to prove

LepVax's safety in endemic areas — does LepVax work where leprosy exists?
LepVax's efficacy — does LepVax prevent leprosy?
LepVax dosage — can we aim for fewer than three doses, which is what we have now?

Where the bottleneck comes in: funding and manufacturing

If the science exists, what is keeping the progress for developing LepVax from coming to fruition?

Before beginning on the Phase 1b Trial with 54 adults in an endemic area, we need to work on a few priority areas, with the chief of these being acquiring more funding. At this point, we have met 32 percent of funding needs, and we still are looking for a total of $1.037 million USD before manufacturing can start.

After the funding is secured, the next milestones can proceed. These include completing manufacturing, implementing the Phase 1b Trial in Rio de Janeiro, identifying a commercial partner to take LepVax production and distribution to a global scale, and strengthening partnerships to ensure the rollout goes smoothly.

“A leprosy-specific vaccine is no longer a dream. It is in development, and it is within reach," Rivoire said.

Project status timeline

2020: Phase 1a complete (USA) — LepVax is proven to be safe in healthy adults, which marks the first time the vaccine is successfully tested in people.

2026: Manufacturing in queue — This will start once Phase 1b funding is secure.

2027: Phase 1b Trial (Brazil) — Researchers will conduct an approved study on 54 adults in an endemic area.

2029+: Phase 2/3 trials — This is a seven-year trial window.

~2038: Vaccine reaches people — Following regulatory approval and WHO prequalification, LepVax will be available for use.

Closing: A vaccine is a justice issue

Ultimately, millions of people are affected by leprosy, and stigma and discrimination against the disease taints countries across the globe. The development of LepVax has the power to turn this narrative around.

Dr Alice Cruz, a social anthropologist, offered a human-rights lens for the vaccine's development that should shape our efforts moving forward. She suggested that those working towards a vaccine should have conversations more often that include persons affected by leprosy. She said we can't just co-produce knowledge — science and experience work hand-in-hand, and experiental knowledge brings insight that straight-forward science cannot grasp. Scientific progress must not repeat old patterns of exclusion, and following this line of thought, a leprosy vaccine will only be successful if people affected by leprosy are treated as partners, not merely as recipients.

Dr Paula Brandão is a nurse and teacher affected by leprosy, and she has supported and advocated for the rights of persons affected by leprosy. Brandão stressed that vaccination is a right, and every person should have the right to access technologies that prevent transmissable diseases.

“We have the right to protection and care. How long will Hansen’s disease continue to be neglected?" Brandão said. "How long will we wait for a vaccine that protects us, our families and our communities?"