Developing Cross Protective Vaccine to Control Leptospira Infection

About This Grant

Developing a cross-protective vaccine to control Leptospira infection Project Summary Leptospirosis is a leading zoonotic cause of human morbidity and mortality, occurring in diverse epidemiologic settings, with estimates of 1.03 million cases and 58,000 deaths per year. It is one of the underrecognized and neglected diseases of humans and animals with similar clinical manifestations. The presence of numerous Leptospira species/serovars, infecting a broad range of animal reservoirs and the resulting environmental contamination, makes control and prevention in humans and animals a cumbersome task. The bacterin-based vaccines available for animals do not offer complete protection or prevent renal colonization and urinary shedding. Due to these limitations and adverse effects, vaccination of humans is not practiced. A broader cross-protective vaccine is urgently needed to prevent Leptospira infection in humans and animals. The availability of a large number of genome sequences and advanced bioinformatics tools has allowed us to use reverse and structural vaccinology approaches to identify a repertoire of conserved antigenic epitopes from Leptospira. Probing these epitopes using a high- throughput microarray and serum from naturally infected animals resulted in identifying proteins that are exposed to the host immune system. In the proposed research, we will confirm their surface exposure and evaluate their protective efficacy in hamsters and mice. Our proposed strategy will overcome the traditional linear, time-consuming, and cost-prohibitive process of antigen discovery for vaccine design. We expect that the vaccination with a cocktail of selected candidates will induce a focused protective response toward relevent immunogenic protein regions. Our long-term goal is to develop a safe and cross-protective vaccine that provides long- lasting immunity against Leptospira infection irrespective of infecting Leptospira serovar and affected host species. Leptospirosis is a globally significant human and animal health problem and a perfect paradigm for an infectious disease of “one health” importance. Development of a cross-protective multispecies vaccine is highly desirable to control this disease, and such a product will have public health, economic, and social impact.