Abstract
Leptospirosis vaccines with higher potency and reduced adverse effects are needed for human use. The carboxyl terminal domain of leptospiral immunoglobulin like protein A (LigAc) is currently the most promising candidate antigen for leptospirosis subunit vaccine. However, LigAc-based vaccines were unable to confer sterilizing immunity against Leptospira infection in animal models. Several factors including antigen properties, adjuvant, delivery system, and administration route need optimization to maximize vaccine efficacy. Our previous report demonstrated protective effects of the recombinant LigAc (rLigAc) formulated with liposome-based adjuvant, called LMQ (neutral liposome combined with monophosphoryl lipid A and Quillaja saponaria fraction 21) in hamsters. This study aimed to evaluate the impact of two commonly used administration routes, intramuscular (IM) and subcutaneous (SC), on immunogenicity and protective efficacy of rLigAc-LMQ administrated three times at 2-week interval. Two IM vaccinations triggered significantly higher levels of total anti-rLigAc IgG than two SC injections. However, comparable IgG titers and IgG2/IgG1 ratio was observed for both routes after the third immunization. The route of vaccine administration did not influence the survival rate (60%) and renal colonization against lethal Leptospira challenge. Importantly, the kidneys of IM group showed no pathological lesions while the SC group showed mild damage. In conclusion, IM vaccination with rLigAc-LMQ not only elicited faster antibody production but also protected from kidney damage following leptospiral infection better than SC immunization. However, both tested routes did not influence protective efficacy in terms of survival rate and the level of renal colonization.
Highlights
Leptospirosis, caused by pathogenic Leptospira spp., is a neglected zoonosis affecting humans and animals mainly in poor sanitary and rural areas
All protocols involving manipulation of hamsters were approved by the Institutional Animal Care and Use Committee (IACUC)—the Armed
His-tagged recombinant LigAc (rLigAc) was produced in E. coli as inclusion bodies
Summary
Leptospirosis, caused by pathogenic Leptospira spp., is a neglected zoonosis affecting humans and animals mainly in poor sanitary and rural areas. The pathogenic bacteria may persist in asymptomatic carriers and cause chronic infection of the renal tubules in various wild and domestic animals. Pathogenic leptospires enter across broken skin or mucus membrane and subsequently penetrate and disseminate hematogenously to target organs resulting in multiple organ dysfunction, such as tubulointerstitial nephritis, jaundice, liver failure, pulmonary hemorrhage, and myocarditis [1,3]. Inactivated whole-cell vaccines for leptospirosis are commercially available, they have not been widely acceptable for human use because they confer short-term immunity, restrict cross-protection among pathogenic serovars, and induce several adverse effects such as local edema, pain, and fever [4]. The variable carboxy-terminal domain 7–13 of leptospiral immunoglobulin-like protein
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