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

Silva, João Guilherme Lino da; Gonçalves, Ana Alice Maia; Oliveira, Liliam Teixeira; Garcia, Giani Martins; Batista, Maurício Azevedo; Mendonça, Ludmila Zanandreis de; Viana, Kelvinson Fernandes; Sant’Ana, Rita de Cássia Oliveira; Melo Júnior, Otoni Alves de Oliveira; Silveira-Lemos, Denise; Dutra, Walderez Ornelas; Martins-Filho, Olindo Assis; Galdino, Alexsandro Sobreira; de Moura, Sandra Aparecida Lima; Mosqueira, Vanessa Carla Furtado; Giunchetti, Rodolfo Cordeiro

doi:10.3390/vaccines11081309

Open AccessArticle

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

by

João Guilherme Lino da Silva

^1,2,†

,

Ana Alice Maia Gonçalves

^1,†

,

Liliam Teixeira Oliveira

³,

Giani Martins Garcia

³,

Maurício Azevedo Batista

¹,

Ludmila Zanandreis de Mendonça

¹,

Kelvinson Fernandes Viana

¹,

Rita de Cássia Oliveira Sant’Ana

¹,

Otoni Alves de Oliveira Melo Júnior

¹,

Denise Silveira-Lemos

⁴,

Walderez Ornelas Dutra

^1,5,

Olindo Assis Martins-Filho

⁶,

Alexsandro Sobreira Galdino

⁷

,

Sandra Aparecida Lima de Moura

⁸,

Vanessa Carla Furtado Mosqueira

³

and

Rodolfo Cordeiro Giunchetti

^1,5,*

¹

Laboratory of Biology of Cell Interactions, Department of Morphology, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil

²

Nucleus for Research in Biological Sciences (NUPEB), Federal University of Ouro Preto, Ouro Preto 35400-000, Brazil

³

Laboratory of Pharmaceutics and Nanotechnology (LDGNano), School of Pharmacy, Federal University of Ouro Preto, Ouro Preto 35400-000, Brazil

⁴

Integrated Research Group on Biomarkers, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte 30190-009, Brazil

⁵

National Institute of Science and Technology in Tropical Diseases, INCT-DT, Salvador 40110-060, Brazil

⁶

Laboratory of Diagnosis and Monitoring Biomarkers, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte 30190-009, Brazil

⁷

Laboratory of Microorganism Biotechnology, Federal University of São João Del-Rei (UFSJ), Midwest Campus, Divinópolis 35501-296, Brazil

⁸

Laboratory of Biomaterials and Experimental Pathology, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35402-136, Brazil

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Vaccines 2023, 11(8), 1309; https://doi.org/10.3390/vaccines11081309

Submission received: 26 April 2023 / Revised: 13 July 2023 / Accepted: 18 July 2023 / Published: 31 July 2023

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies: Edition II)

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Abstract

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.

Keywords: visceral leishmaniasis; submicrometric particles; vaccine; polymeric nanoparticles

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MDPI and ACS Style

Silva, J.G.L.d.; Gonçalves, A.A.M.; Oliveira, L.T.; Garcia, G.M.; Batista, M.A.; Mendonça, L.Z.d.; Viana, K.F.; Sant’Ana, R.d.C.O.; Melo Júnior, O.A.d.O.; Silveira-Lemos, D.; et al. Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity. Vaccines 2023, 11, 1309. https://doi.org/10.3390/vaccines11081309

AMA Style

Silva JGLd, Gonçalves AAM, Oliveira LT, Garcia GM, Batista MA, Mendonça LZd, Viana KF, Sant’Ana RdCO, Melo Júnior OAdO, Silveira-Lemos D, et al. Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity. Vaccines. 2023; 11(8):1309. https://doi.org/10.3390/vaccines11081309

Chicago/Turabian Style

Silva, João Guilherme Lino da, 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, and et al. 2023. "Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity" Vaccines 11, no. 8: 1309. https://doi.org/10.3390/vaccines11081309

APA Style

Silva, J. G. L. d., Gonçalves, A. A. M., Oliveira, L. T., Garcia, G. M., Batista, M. A., Mendonça, L. Z. d., Viana, K. F., Sant’Ana, R. d. C. O., Melo Júnior, O. A. d. O., Silveira-Lemos, D., Dutra, W. O., Martins-Filho, O. A., Galdino, A. S., de Moura, S. A. L., Mosqueira, V. C. F., & Giunchetti, R. C. (2023). Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity. Vaccines, 11(8), 1309. https://doi.org/10.3390/vaccines11081309

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

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