Abstract
Vaccination is the most effective tool against infectious diseases. Subunit vaccines are safer compared to live-attenuated vaccines but are less immunogenic and need to be delivered with an adjuvant. Adjuvants are essential for enhancing vaccine potency by improving humoral and cell-mediated immune responses. Only a limited number of adjuvants are licensed for human vaccines, and their mode of action is still not clear. Leishmania eukaryotic initiation factor (LeIF) has been described having a dual role, as a natural adjuvant and as an antigen that possesses advantageous immunomodulatory properties. In this study, we assessed the adjuvant properties of recombinant Leishmania infantum eukaryotic initiation factor (LieIF) through in vitro and in vivo assays. LieIF was intraperitoneally administered in combination with the protein antigen ovalbumin (OVA), and the widely used alum was used as a reference adjuvant. Our in vitro studies using J774A.1 macrophages showed that LieIF induced stimulatory effects as demonstrated by the enhanced surface expression of CD80 and CD86 co-stimulatory molecules and the induced production of the immune mediators NO and MIP-1α. Additionally, LieIF co-administration with OVA in an in vivo murine model induced a proinflammatory environment as demonstrated by the elevated expression of TNF-α, IL-1β, and NF-κB2 genes in peritoneal exudate cells (PEC). Furthermore, PEC derived from OVA-LieIF-immunized mice exhibited elevated expression of CD80 molecule and production of NO and MIP-1α in culture supernatants. Moreover, LieIF administration in the peritoneum of mice resulted in the recruitment of neutrophils and monocytes at 24 h post-injection. Also, we showed that this immunopotentiating effect of LieIF did not depend on the induction of uric acid danger signal. These findings suggest the potential use of LieIF as adjuvant in new vaccine formulations against different infectious diseases.
Highlights
Vaccines are an indisputable achievement of medical science since millions of lives have been saved from infectious diseases, while they contribute significantly in reducing healthcare expenditure [1]
The phenotypic changes of murine macrophages in response to Leishmania infantum eukaryotic initiation factor (LieIF) were analyzed; since the expression of co-stimulatory molecules (e.g., CD80, CD86) on antigen-presenting cells (APCs), macrophages, and dendritic cells (DCs) is critical in shaping the extent and nature of immune responses [37]
FACS analysis showed that stimulation of J774A.1 macrophages with LieIF induced a significant increase in the expression of CD80 and CD86 costimulatory molecules in terms of median fluorescent intensity (MFI) (Figures 4(a) and 4(c)) along with the percentage (%) of J774A.1 cells (Figures 4(b) and 4(c))
Summary
Vaccines are an indisputable achievement of medical science since millions of lives have been saved from infectious diseases, while they contribute significantly in reducing healthcare expenditure [1]. There are still several diseases that cause significant morbidity and mortality worldwide because either there is no access to vaccine market or the existing vaccines confer suboptimal protection. Another factor is the emergence of new pathogens or reemergence of old ones [2]. New technologies divided into three major categories related to antigen discovery, adjuvants and vaccine vector delivery and deciphering human immune responses, have recently been developed providing a revolution in vaccine development [3]. The term adjuvant, derived from the Latin word adjuvare that means “to help” [4], comprises all compounds that have the ability to enhance and/or shape antigen-specific immune responses [5, 6]. Identification and determination of mode of action of potent adjuvants are important for vaccine discovery [7]
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