Abstract
Leptospirosis is the most widespread zoonosis in the world and a neglected tropical disease estimated to cause severe infection in more than one million people worldwide every year that can be combated by effective immunization. However, no significant progress has been made on the leptospirosis vaccine since the advent of bacterins over 100 years. Although protective against lethal infection, particularly in animals, bacterin-induced immunity is considered short term, serovar restricted, and the vaccine can cause serious side effects. The urgent need for a new vaccine has motivated several research groups to evaluate the protective immune response induced by recombinant vaccines. Significant protection has been reported with several promising outer membrane proteins, including LipL32 and the leptospiral immunoglobulin-like proteins. However, efficacy was variable and failed to induce a cross-protective response or sterile immunity among vaccinated animals. As hundreds of draft genomes of all known Leptospira species are now available, this should aid novel target discovery through reverse vaccinology (RV) and pangenomic studies. The identification of surface-exposed vaccine candidates that are highly conserved among infectious Leptospira spp. is a requirement for the development of a cross-protective universal vaccine. However, the lack of immune correlates is a major drawback to the application of RV to Leptospira genomes. In addition, as the protective immune response against leptospirosis is not fully understood, the rational use of adjuvants tends to be a process of trial and error. In this perspective, we discuss current advances, the pitfalls, and possible solutions for the development of a universal leptospirosis vaccine.
Highlights
A Universal Vaccine against LeptospirosisReviewed by: Arup Sarkar, Trident Academy of Creative Technology, India Carla Pagliari, University of São Paulo, Brazil
Following the discovery of leptospirosis, it was primarily associated with rural populations [1]
The first report of protein-based protection came from studies of recombinant OmpL1 and LipL41 in the hamster model [49], and only 1/3 experiments demonstrated significant protection, this provided the initial impetus for further research into proteinbased vaccine candidates against leptospirosis
Summary
Reviewed by: Arup Sarkar, Trident Academy of Creative Technology, India Carla Pagliari, University of São Paulo, Brazil. Protective against lethal infection, in animals, bacterin-induced immunity is considered short term, serovar restricted, and the vaccine can cause serious side effects. Efficacy was variable and failed to induce a cross-protective response or sterile immunity among vaccinated animals. The identification of surface-exposed vaccine candidates that are highly conserved among infectious Leptospira spp. is a requirement for the development of a cross-protective universal vaccine. As the protective immune response against leptospirosis is not fully understood, the rational use of adjuvants tends to be a process of trial and error. In this perspective, we discuss current advances, the pitfalls, and possible solutions for the development of a universal leptospirosis vaccine
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