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Leptospira Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis.

Authors :
Varma, Vivek P.
Kadivella, Mohammad
Kavela, Sridhar
Faisal, Syed M.
Source :
Vaccines; Dec2023, Vol. 11 Issue 12, p1824, 25p
Publication Year :
2023

Abstract

Leptospirosis is a globally significant zoonotic disease. The current inactivated vaccine offers protection against specific serovars but does not provide complete immunity. Various surface antigens, such as Leptospira immunoglobulin-like proteins (LigA and LigB), have been identified as potential subunit vaccine candidates. However, these antigens require potent adjuvants for effectiveness. Bacterial lipopolysaccharides (LPSs), including lipid A, are a well-known immunostimulant, and clinical adjuvants often contain monophosphoryl lipid A (MPLA). Being less endotoxic, we investigated the adjuvant properties of lipid A isolated from L. interrogans serovar Pomona (PLA) in activating innate immunity and enhancing antigen-specific adaptive immune responses. PLA activated macrophages to a similar degree as MPLA, albeit at a higher dose, suggesting that it is less potent in stimulation than MPLA. Mice immunized with a variable portion of LigA (LAV) combined with alum and PLA (LAV-alum-PLA) exhibited significantly higher levels of LAV-specific humoral and cellular immune responses compared to alum alone but similar to those induced by alum-MPLA. The adjuvant activity of PLA resembles that of MPLA and is primarily achieved through the increased recruitment, activation, and uptake of antigens by innate immune cells. Furthermore, like MPLA, PLA formulation establishes a long-lasting memory response. Notably, PLA demonstrated superior potency than MPLA formulation and provided sterilizing immunity against the leptospirosis in a hamster model. Overall, our study sheds light on the adjuvant properties of Leptospira lipid A and offers promising avenues for developing LPS-based vaccines against this devastating zoonotic disease. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
2076393X
Volume :
11
Issue :
12
Database :
Complementary Index
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
174493855
Full Text :
https://doi.org/10.3390/vaccines11121824