PLGA nanoparticle-delivered Leishmania antigen and TLR agonists as a therapeutic vaccine against cutaneous leishmaniasis in BALB/c mice

• Published in: International immunopharmacology 2024-09, Vol.138, p.112538, Article 112538
• Main Authors: Katebi, Asal, Riazi-rad, Farhad, Varshochian, Reyhaneh, Ajdary, Soheila
• Format: Article
• Language: English
• Subjects: Cutaneous leishmaniasis; Pam3CSK4; PLGA nanoparticles; R848; Therapeutic vaccine
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112538

[Display omitted] •PLGA nanoparticles loaded with SLA and TLR agonists R848 and Pam3CSK4 (PLGA NPs (SLA-R848-Pam3CSK4)) can be used as a therapeutic vaccine against L. major infection in BALB/C mice.•PLGA NPs (SLA-R848-Pam3CSK4) control the disease by reducing footpad swelling and parasite burden.•PLGA NPs (SLA-R848-Pam3CSK4) enhance Th1-based immune responses through the induction of IFN-γ, NO, and IgG2a antibodies. Leishmaniasis, caused by Leishmania (L.) species, remains a neglected infection. Therapeutic vaccination presents a promising strategy for its treatment. In this study, we aimed to develop a therapeutic vaccine candidate using Leishmaniaantigens (SLA) and Toll-like receptor (TLR) 7/8 agonist (R848) encapsulated into the poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Moreover, TLR1/2 agonist (Pam3CSK4) was loaded onto the NPs. The therapeutic effects of these NPs were evaluated in L. major-infected BALB/c mice. Footpad swelling, parasite load, cellular and humoral immune responses, and nitric oxide (NO) production were analyzed. The results demonstrated that the PLGA NPs (SLA-R848-Pam3CSK4) therapeutic vaccine effectively stimulated Th1 cell responses, induced humoral responses, promoted NO production, and restricted parasite burden and lesion size.Our findings suggest that vaccination with SLA combined with TLR1/2 and TLR7/8 agonists in PLGA NPs as a therapeutic vaccine confers strong protection againstL. majorinfection. These results represent a novel particulate therapeutic vaccine against Old World cutaneous leishmaniasis.