Evaluation of different strategies to promote a protective immune response against leptospirosis using a recombinant LigA and LigB chimera

Abstract

Leptospirosis is a zoonosis of worldwide distribution, caused by infection with pathogenic Leptospira species. The vaccines that are currently available are bacterins, with limited human use, that confer short-term, serovar-specific immunity. Lig proteins are considered to be the best vaccine candidates to date. Here, we aimed to construct a recombinant Lig chimera (LC) comprised of LigAni and LigBrep fragments, and to evaluate it as subunit or DNA vaccine using different administration strategies. Vaccines were formulated with 50 µg of recombinant LC associated with different adjuvants or with 100 µg of pTARGET/LC. Four-week-old hamsters received two doses of vaccine with different strategies and were challenged with 5 × DL₅₀Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. The immune response generated by Lig chimera conferred 100% protection to hamsters treated with at least one dose of recombinant LC. Despite the high levels of antibodies that vaccinated animals produced, a sterilizing immunity was not achieved. The lack of a sterilizing immunity could indicate the importance of a mixed humoral and cellular immune response. The present study generated insights that will be useful in the future development of improved subunit vaccines against leptospirosis.

Keywords: DNA vaccine; Leptospira; Leptospiral Immunoglobulin-like; Protection; Subunit vaccine.