Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity

Autor: João Guilherme Lino da Silva, Ana Alice Maia Gonçalves, Liliam Teixeira Oliveira, Giani Martins Garcia, Maurício Azevedo Batista, Ludmila Zanandreis de Mendonça, Kelvinson Fernandes Viana, Rita de Cássia Oliveira Sant’Ana, Otoni Alves de Oliveira Melo Júnior, Denise Silveira-Lemos, Walderez Ornelas Dutra, Olindo Assis Martins-Filho, Alexsandro Sobreira Galdino, Sandra Aparecida Lima de Moura, Vanessa Carla Furtado Mosqueira, Rodolfo Cordeiro Giunchetti
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Vaccines, Vol 11, Iss 8, p 1309 (2023)
Druh dokumentu: article
ISSN: 11081309
2076-393X
DOI: 10.3390/vaccines11081309
Popis: Recent studies suggest that the association of antigens in microparticles increases the anti-Leishmania vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(D,L-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP1, containing poly(D,L-lactide) (PLA) 1% wt/v and chitosan 1% wt/v; and SMP2, containing PLA 5% wt/v and chitosan 5% wt/v. After a single dose of the unloaded SMP1 or SMP2 in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-β-D-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the Leishmania braziliensis antigen was encapsulated in SMPs (SMP1Ag and SMP2Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3−CD49+) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3+CD4+) and CD3+CD8+) and B cells (CD19+) of the SMP2 group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered Leishmania antigens.
Databáze: Directory of Open Access Journals
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