Intranasal vaccine from whole Leishmania ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis.
Author(s) :
Helou, Doumet Georges [Auteur]
Université Paris Cité [UPCité]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Mauras, A. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Fasquelle, Francois [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Lanza, J. S. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Loiseau, P. M. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Betbeder, Didier [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Cojean, S. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Université Paris Cité [UPCité]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Mauras, A. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Fasquelle, Francois [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Lanza, J. S. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Loiseau, P. M. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Betbeder, Didier [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Cojean, S. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Journal title :
PLoS Neglected Tropical Diseases
Abbreviated title :
PLoS Negl Trop Dis
Volume number :
15
Pages :
e0009627
Publication date :
2021-08-22
ISSN :
1935-2735
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects ...
Show more >Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects are not uncommon. Moreover, an approved vaccine against human leishmaniasis does not exist yet. Using whole antigens from Leishmania donovani promastigotes (LdAg), we investigated the protective potential of a novel adjuvant-free vaccine strategy. Immunization of mice with LdAg via the intradermal or the intranasal route prior to infection decreases the parasitic burden in primary affected internal organs, including the liver, spleen, and bone marrow. Interestingly, the intranasal route is more efficient than the intradermal route, leading to better parasite clearance and remarkable induction of adaptive immune cells, notably the helper and cytotoxic T cells. In vitro restimulation experiments with Leishmania antigens led to significant IFN-γ secretion by splenocytes; therefore, exemplifying specificity of the adaptive immune response. To improve mucosal delivery and the immunogenic aspects of our vaccine strategy, we used polysaccharide-based nanoparticles (NP) that carry the antigens. The NP-LdAg formulation is remarkably taken up by dendritic cells and induces their maturation in vitro, as revealed by the increased expression of CD80, CD86 and MHC II. Intranasal immunization with NP-LdAg does not improve the parasite clearance in our experimental timeline; however, it does increase the percentage of effector and memory T helper cells in the spleen, suggesting a potential induction of long-term memory. Altogether, this study provides a simple and cost-effective vaccine strategy against visceral leishmaniasis based on LdAg administration via the intranasal route, which could be applicable to other parasitic diseases.Show less >
Show more >Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects are not uncommon. Moreover, an approved vaccine against human leishmaniasis does not exist yet. Using whole antigens from Leishmania donovani promastigotes (LdAg), we investigated the protective potential of a novel adjuvant-free vaccine strategy. Immunization of mice with LdAg via the intradermal or the intranasal route prior to infection decreases the parasitic burden in primary affected internal organs, including the liver, spleen, and bone marrow. Interestingly, the intranasal route is more efficient than the intradermal route, leading to better parasite clearance and remarkable induction of adaptive immune cells, notably the helper and cytotoxic T cells. In vitro restimulation experiments with Leishmania antigens led to significant IFN-γ secretion by splenocytes; therefore, exemplifying specificity of the adaptive immune response. To improve mucosal delivery and the immunogenic aspects of our vaccine strategy, we used polysaccharide-based nanoparticles (NP) that carry the antigens. The NP-LdAg formulation is remarkably taken up by dendritic cells and induces their maturation in vitro, as revealed by the increased expression of CD80, CD86 and MHC II. Intranasal immunization with NP-LdAg does not improve the parasite clearance in our experimental timeline; however, it does increase the percentage of effector and memory T helper cells in the spleen, suggesting a potential induction of long-term memory. Altogether, this study provides a simple and cost-effective vaccine strategy against visceral leishmaniasis based on LdAg administration via the intranasal route, which could be applicable to other parasitic diseases.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2024-01-12T06:11:46Z
2024-02-28T15:37:41Z
2024-02-28T15:37:41Z
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