Abstract
BackgroundLeptospirosis is an important zoonotic disease worldwide. Humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. Such complications are thought to depend on several factors, including the host immunity. Protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired Leptospira infection.Methods and principal findingsHere, we used protein microarray chip to profile the antibody responses of patients with severe and mild leptospirosis against the complete Leptospira interrogans serovar Copenhageni predicted ORFeome. We discovered a limited number of immunodominant antigens, with 36 antigens specific to patients, of which 11 were potential serodiagnostic antigens, identified at acute phase, and 33 were potential subunit vaccine targets, detected after recovery. Moreover, we found distinct antibody profiles in patients with different clinical outcomes: in the severe group, overall IgM responses do not change and IgG responses increase over time, while both IgM and IgG responses remain stable in the mild patient group. Analyses of individual patients’ responses showed that >74% of patients in the severe group had significant IgG increases over time compared to 29% of patients in the mild group. Additionally, 90% of IgM responses did not change over time in the mild group, compared to ~51% in the severe group.ConclusionsIn the present study, we detected antibody profiles associated with disease severity and speculate that patients with mild disease were protected from severe outcomes due to pre-existing antibodies, while patients with severe leptospirosis demonstrated an antibody profile typical of first exposure. Our findings represent a significant advance in the understanding of the humoral immune response to Leptospira infection, and we have identified new targets for the development of subunit vaccines and diagnostic tests.
Highlights
Leptospirosis causes over one million cases and nearly 60,000 deaths annually, with the greatest disease burden in urban slums in tropical and subtropical countries [1,2,3]
We detected antibody profiles associated with disease severity and speculate that patients with mild disease were protected from severe outcomes due to preexisting antibodies, while patients with severe leptospirosis demonstrated an antibody profile typical of first exposure
Our findings represent a significant advance in the understanding of the humoral immune response to Leptospira infection, and we have identified new targets for the development of subunit vaccines and diagnostic tests
Summary
Leptospirosis causes over one million cases and nearly 60,000 deaths annually, with the greatest disease burden in urban slums in tropical and subtropical countries [1,2,3]. The factors contributing to disease severity remain poorly understood, but bacterial virulence, inoculum dose and the host immune response are thought to play important roles in development of severe outcomes [2, 4]. Passive transfer of whole cell leptospiral vaccine and specific anti-leptospiral antibodies (Ligs) are protective against homologous infection in animal models, demonstrating antibodies are sufficient for immunity against experimental homologous infection [10,11,12,13]. Humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. Such complications are thought to depend on several factors, including the host immunity. Protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired Leptospira infection.
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