Leprosy is curable, and the medicine is free. Yet every year more than 170,000 people are newly diagnosed, and that number has barely fallen in a decade. Today’s cure, multidrug therapy (MDT), kills the bacteria that causes the disease, stopping active infection. But nerve damage that is already established when treatment begins may be permanent, making the success of MDT in preventing disability heavily dependent on the timing of diagnosis. Likewise, although a patient becomes non-contagious within just a few days of starting MDT, close contacts can be exposed or infected during the period before diagnosis. In other words, MDT is a valuable tool, but it is not enough by itself to eliminate leprosy. To make progress against the disease, we need more tools. Hope Rises International believes in the potential of LepVax, the world’s first vaccine designed specifically for leprosy, to become a safe and effective tool.

A leprosy-specific vaccine

Traditional vaccine development for leprosy has not been possible because the bacterium that causes the disease, Mycobacterium leprae, cannot be grown in a laboratory petri dish or culture. The next-best solution has been to use the BCG vaccine developed for tuberculosis. M. leprae and M. tuberculosis are closely related mycobacteria, and BCG offers some cross-protection. However, the protection is partial, variable, and wanes over time.

Genome sequencing of M. leprae, completed and published in 2001, opened new ways to design a vaccine without needing to grow the bacterium in the lab. Using reverse vaccinology, LepVax researchers identified four M. leprae proteins that could stimulate a protective T-cell response. They joined the genes for these proteins into a single engineered protein called LEP-F1, and then mixed it with GLA-SE, an ingredient that helps to trigger a strong immune response. The kind of vaccine that they created – made from specific, purified parts of the pathogen’s genome – is called a “defined subunit vaccine.”

Compared to vaccines made from a weakened or killed whole bacterium, like BCG, subunit vaccines are more targeted and less likely to trigger unwanted responses from the immune system. As a subunit vaccine, LepVax has unique potential to improve immune protection while also helping to prevent damage to nerves.¹

Studies and testing

In a laboratory study of armadillos infected with M. leprae, 3 of 24 armadillos vaccinated with LepVax developed sustained nerve damage (12.5%) compared to 21 of 24 unvaccinated armadillos (87.5%). This suggests that, in armadillos at least, vaccination after infection helps to protect nerves from injury.

In a safety study of healthy United States-based adult volunteers with no history of travel to leprosy-endemic countries, LepVax proved safe and well tolerated.²

The next stage in safety testing will take place in Brazil. It is important to test in a leprosy-endemic country because participants may have prior exposure to mycobacteria that could influence immune responses. Researchers want to confirm that the vaccine remains safe and immunogenic in the kind of population where it will matter most.

Hope for the future

The free, effective cure we have today, MDT, does its work after leprosy takes hold. A vaccine like LepVax would make the fight against leprosy less dependent on the timing of treatment. It has the potential to prevent leprosy from taking hold, in effect interrupting transmission, and to protect the nerves of infected persons even before diagnosis. LepVax is not ready to be used yet – there are still many trials that must happen to ensure safety and efficacy – but we know enough to make those trials worth pursuing.

References

¹ “Our studies demonstrate that BCG vaccination precipitates nerve damage in M. leprae-infected armadillos. . . . In direct contrast, immunization with LepVax reduced and significantly delayed nerve damage.” M.S. Duthie, M.T. Pena, G.J. Ebenezer, et al., LepVax, a defined subunit vaccine that provides effective pre-exposure and post-exposure prophylaxis of M. leprae infection, npj Vaccines 3, no. 12 (2018), https://doi.org/10.1038/s41541-018-0050-z.

² M.S. Duthie, A. Frevol, T. Day, R.N. Coler, et al., A phase 1 antigen dose escalation trial to evaluate safety, tolerability and immunogenicity of the leprosy vaccine candidate LepVax (LEP-F1 + GLA–SE) in healthy adults, Vaccine 38, no. 7 (2020): 1700-1707, https://doi.org/10.1016/j.vaccine.2019.12.050.