Abstract
Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins) are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV) has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.
Highlights
The worldwide incidence of leptospirosis is increasing year on year, from an initial estimate of 500,000 cases in 1999 [1] to over one million cases and 60,000 fatalities in 2015 [2]
Rather than select individual proteins for evaluation, the reverse vaccinology (RV) approach analyses the entire genome of the pathogen and uses bioinformatics to reduce the number of potential targets, to approximately 500 proteins, followed by their high-throughput production as recombinant proteins and subsequent evaluation as potential vaccine candidates in the laboratory
We highlight the importance of leptospirosis and the urgent need for the development of new recombinant vaccines, and we focus on the application of RV to leptospirosis
Summary
The worldwide incidence of leptospirosis is increasing year on year, from an initial estimate of 500,000 cases in 1999 [1] to over one million cases and 60,000 fatalities in 2015 [2]. While some progress has been made, the development of a broad-range vaccine remains elusive. During this time, the vaccine candidate discovery process underwent several major advances following the so-called “-omics boom”. The ever-increasing numbers and refinements in the quality of pathogenic genome sequences and bioinformatics tools, combined with advances in pathogenesis and immunology, led to the development and establishment of the process known as reverse vaccinology (RV) [6]. Rather than select individual proteins for evaluation, the RV approach analyses the entire genome of the pathogen and uses bioinformatics to reduce the number of potential targets, to approximately 500 proteins, followed by their high-throughput production as recombinant proteins and subsequent evaluation as potential vaccine candidates in the laboratory. We highlight the importance of leptospirosis and the urgent need for the development of new recombinant vaccines, and we focus on the application of RV to leptospirosis
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