Leptospirosis is the leading zoonotic disease in terms of morbidity and mortality worldwide. Effective prevention is urgently needed as the drivers of disease transmission continue to intensify. The key challenge has been developing a widely applicable vaccine that protects against the >300 serovars that can cause leptospirosis. Live attenuated mutants are enticing vaccine candidates and poorly explored in the field. We evaluated a recently characterized motility-deficient mutant lacking the expression of a flagellar protein, FcpA. Although the fcpA- mutant has lost its ability to cause disease, transient bacteremia was observed. In two animal models, immunization with a single dose of the fcpA- mutant was sufficient to induce a robust anti-protein antibodies response that promoted protection against infection with different pathogenic Leptospira species. Furthermore, characterization of the immune response identified a small repertoire of biologically relevant proteins that are highly conserved among pathogenic Leptospira species and potential correlates of cross-protective immunity.
Keywords: cross-protective immunity; infectious disease; leptospira; leptospirosis; live attenuated vaccine; microbiology.
Leptospirosis is a life-threatening disease with flu-like symptoms that is caused by bacteria known as Leptospira. It is more common in warmer regions with high rainfall, especially in impoverished areas. The disease is spread in the urine of animals such as rodents, farm animals or dogs. Humans and other animals can get leptospirosis when they come in contact with urine-contaminated water and soil. Current measures to control leptospirosis are largely ineffective. Although a vaccine is available for animals, it only protects against a few types of the 300 disease-causing Leptospira bacteria. It also fails to stop the bacteria from colonizing the kidneys of the infected animals, which means that vaccinated animals can still spread disease. Previous research has shown that inactivating a protein called FcpA, which is necessary for Leptospira bacteria to move, can stop them from infecting hamsters. Moreover, when these animals were exposed to the mutant bacteria, they did not get sick nor developed the disease. Here, Wunder et al. tested whether bacteria lacking the FcpA protein could be used as an attenuated vaccine. This form of vaccine contains live bacteria that have been modified to become harmless but are able to train the immune system to produce a long-lasting immune response against the invaders. The results showed that a single dose of the vaccine was enough to prevent hamsters and mice from dying of leptospirosis. It also worked against several types of Leptospira and could stop them from colonizing mice kidneys. Moreover, Wunder et al. found that the immune system targeted specific proteins that were common to various types of Leptospira, which may explain the broad spectrum of protection the vaccine offered. Rapid urbanization and climate change are among the main drivers of leptospirosis. An effective vaccine for this disease would reduce the public health burden by providing protection against leptospirosis and by reducing the spread of the disease. A next step will be to ensure the mutant Leptospira are safe to use in animals and potentially humans.