Polylactide Nanoparticles as a Biodegradable Vaccine Adjuvant: A Study on Safety, Protective Immunity and Efficacy against Human Leishmaniasis Caused by Leishmania Major - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecules Année : 2022

Polylactide Nanoparticles as a Biodegradable Vaccine Adjuvant: A Study on Safety, Protective Immunity and Efficacy against Human Leishmaniasis Caused by Leishmania Major

Résumé

Leishmaniasis is the 3rd most challenging vector-borne disease after malaria and lymphatic filariasis. Currently, no vaccine candidate is approved or marketed against leishmaniasis due to difficulties in eliciting broad immune responses when using sub-unit vaccines. The aim of this work was the design of a particulate sub-unit vaccine for vaccination against leishmaniasis. The poly (D,L-lactide) nanoparticles (PLA-NPs) were developed in order to efficiently adsorb a recombinant L. major histone H2B (L. major H2B) and to boost its immunogenicity. Firstly, a study was focused on the production of well-formed nanoparticles by the nanoprecipitation method without using a surfactant and on the antigen adsorption process under mild conditions. The set-up preparation method permitted to obtain H2B-adsorbed nanoparticles H2B/PLA (adsorption capacity of about 2.8% (w/w)) with a narrow size distribution (287 nm) and a positive zeta potential (30.9 mV). Secondly, an in vitro release assay performed at 37 °C, pH 7.4, showed a continuous release of the adsorbed H2B for almost 21 days (30%) from day 7. The immune response of H2B/PLA was investigated and compared to H2B + CpG7909 as a standard adjuvant. The humoral response intensity (IgG) was substantially similar between both formulations. Interestingly, when challenged with the standard parasite strain (GLC94) isolated from a human lesion of cutaneous leishmaniasis, mice showed a significant reduction in footpad swelling compared to unvaccinated ones, and no deaths occurred until week 17th. Taken together, these results demonstrate that PLA-NPs represent a stable, cost-effective delivery system adjuvant for use in vaccination against leishmaniasis.
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hal-04145316 , version 1 (29-06-2023)

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Sana Ayari-Riabi, Noureddine Ben Khalaf, Balkiss Bouhaouala-Zahar, Bernard Verrier, Thomas Trimaille, et al.. Polylactide Nanoparticles as a Biodegradable Vaccine Adjuvant: A Study on Safety, Protective Immunity and Efficacy against Human Leishmaniasis Caused by Leishmania Major. Molecules, 2022, 27 (24), pp.8677. ⟨10.3390/molecules27248677⟩. ⟨hal-04145316⟩
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