Leptospira borgpetersenii Leucine-Rich Repeat Proteins Provide Strong Protective Efficacy as Novel Leptospiral Vaccine Candidates

Abstract

Leucine-rich repeat (LRR) proteins are advocated for being assessed in vaccine development. Leptospiral LRR proteins were identified recently in silico from the genome of Leptospira borgpetersenii serogroup Sejroe, the seroprevalence of leptospiral infections of cattle in Thailand. Two LRR recombinant proteins, rKU_Sej_LRR_2012M (2012) and rhKU_Sej_LRR_2271 (2271), containing predicted immunogenic epitopes, were investigated for their cross-protective efficacies in an acute leptospirosis model with heterologous Leptospira serovar Pomona, though, strains from serogroup Sejroe are host-adapted to bovine, leading to chronic disease. Since serovar Pomona is frequently reported as seropositive in cattle, buffaloes, pigs, and dogs in Thailand and causes acute and severe leptospirosis in cattle by incidental infection, the serogroup Sejroe LRR proteins were evaluated for their cross-protective immunity. The protective efficacies were 37.5%, 50.0%, and 75.0% based on the survival rate for the control, 2012, and 2271 groups, respectively. Sera from 2012-immunized hamsters showed weak bactericidal action compared to sera from 2271-immunized hamsters (p < 0.05). Therefore, bacterial tissue clearances, inflammatory responses, and humoral and cell-mediated immune (HMI and CMI) responses were evaluated only in 2271-immunized hamsters challenged with virulent L. interrogans serovar Pomona. The 2271 protein induced prompt humoral immune responses (p < 0.05) and leptospiral tissue clearance, reducing tissue inflammation in immunized hamsters. In addition, protein 2271 and its immunogenic peptides stimulated splenocyte lymphoproliferation and stimulated both HMI and CMI responses by activating Th1 and Th2 cytokine gene expression in vaccinated hamsters. Our data suggest that the immunogenic potential renders rhKU_Sej_LRR_2271 protein a promising candidate for the development of a novel cross-protective vaccine against animal leptospirosis.

Enhancement of clinical signs in C3H/HeJ mice vaccinated with a highly immunogenicLeptospiramethyl-accepting chemotaxis protein following challenge

“…In our study MCP antigen elicited significant IgG antibody levels in immunized C3H/HeJ mice, predominantly IgG1 and IgG2a isotypes but minimal IgG3, despite the lack of protection. Factors associated with correlates of protection are still unknown in cases of leptospirosis (17,19,21,22,(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81). In fact, our study reinforces the need to improve our understanding of the protective immune responses against leptospirosis, especially the role of cellular immune response, which is poorly evaluated in experimental vaccines tested in the hamster model.…”

Comparative membrane proteomic analysis of Tritrichomonas foetus isolates

“…On the other hand, in Bacteroides forsythus, the BspA protein has been postulated as a target for the host immune response 95 . In the case of the bacteria Leptospira borgpetersenii, the recombinant modified leucine-rich repeat protein rhKU_Sej_LRR_2271 has been suggested as a candidate for leptospiral vaccine development 96 . Finally, the same recombinant protein was used to develop a lateral flow strip test for the detection of anti-leptospiral IgG in dogs 97 .…”

Human leptospirosis: In search for a better vaccine

“…In silico studies, two Leptospira LRR proteins, rKU_Sej_LRR_2012M (LRR2012) and rKU_Sej_LRR_2271 (LRR2271) from L. borgpetersenii were identified and subsequently tested in a hamster model 155 . The study observed that 50% of animals immunized with LRR2012 and 75% of animals immunized with LRR2271 recombinant proteins were protected when challenged with Pomona serovar.…”

“…The study observed that 50% of animals immunized with LRR2012 and 75% of animals immunized with LRR2271 recombinant proteins were protected when challenged with Pomona serovar. In addition, the LRR2271 protein induced a strong humoral response and activated the expression of cytokine genes related to Th1 and Th2 responses 155 …”

“…In addition, the LRR2271 protein induced a strong humoral response and activated the expression of cytokine genes related to Th1 and Th2 responses. 155…”