Reduced Renal Colonization and Enhanced Protection by Leptospiral Factor H Binding Proteins as a Multisubunit Vaccine against Leptospirosis in Hamsters

Abstract

Subunit vaccines conferring complete protection against leptospirosis are not currently available. The interactions of factor H binding proteins (FHBPs) on pathogenic leptospires and host factor H are crucial for immune evasion by inhibition of complement-mediated killing. The inhibition of these interactions may be a potential strategy to clear leptospires in the host. This study aimed to evaluate a multisubunit vaccine composed of four known leptospiral FHBPs: LigA domain 7–13 (LigAc), LenA, LcpA, and Lsa23, for its protective efficacy in hamsters. The mono and multisubunit vaccines formulated with LMQ adjuvant, a combination of neutral liposome, monophosphoryl lipid A, and Quillaja saponaria fraction 21, induced high and comparable specific antibody (IgG) production against individual antigens. Hamsters immunized with the multisubunit vaccine showed 60% survival following the challenge by 20 LD50 of Leptospira interrogans serovar Pomona. No significant difference in survival rate and pathological findings of target organs was observed after vaccinations with multisubunit or mono-LigAc vaccines. However, the multisubunit vaccine significantly reduced leptospiral burden in surviving hamsters in comparison with the monosubunit vaccines. Therefore, the multisubunit vaccine conferred partial protection and reduced renal colonization against virulence Leptospira infection in hamsters. Our multisubunit formulation could represent a promising vaccine against leptospirosis.

A Comparison of Intramuscular and Subcutaneous Administration of LigA Subunit Vaccine Adjuvanted with Neutral Liposomal Formulation Containing Monophosphoryl Lipid A and QS21

“…The rLigAc was produced as described previously [11]. Briefly, inclusion bodies were isolated by centrifugation, washed with Tris buffer, pH 8.0 (50 mM Tris and 200 mM NaCl) containing 0.5% Triton X-100 and 1 M urea at 4 • C for 3 h, and solubilized in Tris buffer containing 6 M urea and 5 mM DTT overnight at 4 • C. The extracted proteins were purified by Ni 2+ Chelating Sepharose column (GE Healthcare, Buckinghamshire, UK) under denaturing conditions.…”

“…The variable carboxy-terminal domain 7-13 of leptospiral immunoglobulin-like protein A (LigAc) is currently the most promising antigen for leptospirosis vaccines [5][6][7]. Different types and formulations of LigAc-based vaccines, including DNA [8,9], recombinant single subunit [5][6][7], multisubunit [10,11], chimeric [12][13][14] vaccines, delivery systems [15], and adjuvants [16,17], have been tested for their efficacy in animal models. However, all these strategies were unable to completely prevent Leptospira renal colonization and pathological changes.…”

“…Our previous study showed that recombinant LigAc (rLigAc) formulated with a liposome-based adjuvant called LMQ, composed of neutral liposome and two immunostimulants (MPL and QS21), conferred partial protection in hamsters [11] with overall 60% survival rate comparable with those obtained with rLigAc plus Freund's adjuvant and alum [16,25]. To investigate the role of immunization route on the efficacy of rLigAc-LMQ, two common vaccination routes (IM and SC) were evaluated in the present study for the induction of rLigAc-specific antibody and the protective efficacy in hamsters, an animal model of acute leptospirosis.…”

Investigating the Immunological and Biological Equilibrium of Reservoir Hosts and Pathogenic Leptospira: Balancing the Solution to an Acute Problem?

“…Interestingly, this phenomenon is also host species specific. Calves challenged with L. interrogans serovar Pomona resulted in hemoglobinemia and RBC damage and abnormalities (Thompson, 1986), while these features are not reported in the hamster, despite the fact that hamsters are still susceptible to Pomona (Srinivas et al, 2013;Techawiwattanaboon et al, 2019). In contrast, infection with L. interrogans serovar Ballum results in the opposite, with hemoglobinemia and morphological changes seen in the RBCs of the hamster and not in cattle (Thompson and Manktelow, 1986).…”

“…Original magnification 10,000×. (Natarajaseenivasan et al, 2005;Ramirez-Ramirez et al, 2015) SP (Boey et al, 2019) SP (Campos et al, 2017) A (Ojeda et al, 2018;Loureiro and Lilenbaum, 2020) SP (Hamond et al, 2015;Simbizi et al, 2016) A (Hamond et al, 2015) R (Gay et al, 2014) SP (Lee et al, 2017) A (Mitchell et al, 1966) A (Adin and Cowgill, 2000;Greenlee et al, 2005) SP (Goldstein et al, 2006) A (Srinivas et al, 2013;Techawiwattanaboon et al, 2019) Tarassovi A (Maze et al, 2016) SP (Boey et al, 2019) SP (Campos et al, 2017) SP (Simbizi et al, 2016) SP (Lee et al, 2017) R SP (Barmettler et al, 2011) NE Hardjo A (Bolin and Koellner, 1988;Ezeh et al, 1991) R SP (Boey et al, 2019) R* (Ellis et al, 1981;Ellis et al, 1986;Rajala et al, 2017;Loureiro and Lilenbaum, 2020) SP (Campos et al, 2017;Nally et al, 2018a) A (Hamond et al, 2015) SP (Simbizi et al, 2016) SP (Hathaway et al, 1983;Lee et al, 2017) SP (Goldstein et al, 2006;Harland et al, 2013) A (Zuerner et a...…”