Varma, V.P.; Kadivella, M.; Kavela, S.; Faisal, S.M. Leptospira Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis. Vaccines2023, 11, 1824.
Varma, V.P.; Kadivella, M.; Kavela, S.; Faisal, S.M. Leptospira Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis. Vaccines 2023, 11, 1824.
Varma, V.P.; Kadivella, M.; Kavela, S.; Faisal, S.M. Leptospira Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis. Vaccines2023, 11, 1824.
Varma, V.P.; Kadivella, M.; Kavela, S.; Faisal, S.M. Leptospira Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis. Vaccines 2023, 11, 1824.
Abstract
Leptospirosis is a zoonotic disease of global importance. The current killed vaccine provides serovar-specific protection without sterilizing immunity. Several surface antigens, including Leptospira immunoglobulin-like proteins (LigA and LigB), have been identified as subunit vaccine candidates; however, they require potent adjuvants. Bacterial Lipopolysaccharide (LPS), including lipid A, is a well-known immunostimulatory agent, and the formulation of Monophosphoryl Lipid A (MPLA) in Alum is a clinical adjuvant. Being less endotoxic, we tested the adjuvant activity of lipid A purified from L. interrogans serovar Pomona (PLA) for its ability to activate innate and enhance antigen-specific adaptive immune response. PLA-induced activation of macrophages similar to levels induced by MPLA, albeit at a much higher dose, indicating that it is less stimulatory than MPLA. Mice immunized with a Variable portion of LigA (LAV) formulated in Alum and PLA (LAV-Alum-PLA) induced significantly higher levels of LAV-specific humoral and cellular immune response than Alum but similar to levels induced by Alum-MPLA. The adjuvant activity of PLA seems to be quite similar to MPLA and primarily mediated through enhanced recruitment, activation, and uptake of antigens by innate immune cells. Moreover, like MPLA, the PLA formulation was able to generate a long-term memory response. Most importantly, PLA demonstrated better potency than MPLA formulation and generated sterilizing immunity against challenge in a hamster model of leptospirosis. Altogether, our study has provided important insight into the adjuvant activity of Leptospira lipid A and has opened avenues for the development of LPS-based vaccines against this dreadful zoonosis.
Keywords
Lig A; Lipid A; Adjuvant; Vaccine; MPLA; Alum; Leptospirosis
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
