eprintid: 10187327 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/18/73/27 datestamp: 2024-02-19 08:59:25 lastmod: 2025-02-10 11:45:16 status_changed: 2024-02-19 08:59:25 type: article metadata_visibility: show sword_depositor: 699 creators_name: Salgado, Caio Loureiro creators_name: Corea, Andrés Felipe Mendéz creators_name: Covre, Luciana Polaco creators_name: Fonseca-Martins, Alessandra Marcia creators_name: Falqueto, Aloisio creators_name: Guedes, Herbert Leonel DE Matos creators_name: Rossi-Bergmann, Bartira creators_name: Gomes, Daniel Cláudio Oliviera title: Intranasal delivery of LaAg vaccine improves immunity of aged mice against visceral Leishmaniasis ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G94 keywords: Ageing, Intranasal vaccine, Leishmania amazonensis, Visceral leishmaniasis, antigen note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: There are no approved vaccines yet for human visceral leishmaniasis (VL), the most severe form of the leishmaniasis clinical manifestations that is fatal in over 95% of untreated cases. It is well-accepted that immunological changes during ageing have deleterious impact on the efficacy of vaccines and response to infections. In this work, we compared the response of young and aged mice to intranasal vaccination with killed Leishmania amazonensis promastigote antigens (LaAg) that were then challenged with L. infantum infection, a species that causes visceral leishmaniasis. Intranasal vaccination with LaAg induced a similar reduction in parasitism and hepatosplenomegaly in both young and aged mice compared to their unvaccinated counterparts. Following infection, there was also a less prominent inflammatory profile particularly in the vaccinated aged group, with lower production of TNF-α and nitrite compared to the respective unvaccinated group. Interestingly, the LaAg intranasal vaccination promoted increased production of IFN-γ that was observed in both young- and aged vaccinated groups. Additionally, CD4+ and CD8+ T cells from both vaccinated groups presented decreased expression of the inhibitory receptors PD-1 and KLRG1 compared to their unvaccinated controls. Interestingly, a strong positive correlation was observed between the expression of both inhibitory receptors PD-1 and KLRG1 and parasitism, which was more conspicuous in the unvaccinated-aged mice than in the others. Overall, this study helps define new strategies to improve vaccine effectiveness and provides a perspective for prophylactic alternatives against leishmaniasis. date: 2024-04-25 date_type: published publisher: Elsevier BV official_url: http://dx.doi.org/10.1016/j.actatropica.2024.107125 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2245222 doi: 10.1016/j.actatropica.2024.107125 pii: S0001-706X(24)00009-3 lyricists_name: Polaco Covre, Luciana lyricists_id: LPOLA68 actors_name: Polaco Covre, Luciana actors_id: LPOLA68 actors_role: owner full_text_status: public publication: Acta Tropica volume: 252 article_number: 107125 event_location: Netherlands issn: 0001-706X citation: Salgado, Caio Loureiro; Corea, Andrés Felipe Mendéz; Covre, Luciana Polaco; Fonseca-Martins, Alessandra Marcia; Falqueto, Aloisio; Guedes, Herbert Leonel DE Matos; Rossi-Bergmann, Bartira; Salgado, Caio Loureiro; Corea, Andrés Felipe Mendéz; Covre, Luciana Polaco; Fonseca-Martins, Alessandra Marcia; Falqueto, Aloisio; Guedes, Herbert Leonel DE Matos; Rossi-Bergmann, Bartira; Gomes, Daniel Cláudio Oliviera; - view fewer <#> (2024) Intranasal delivery of LaAg vaccine improves immunity of aged mice against visceral Leishmaniasis. Acta Tropica , 252 , Article 107125. 10.1016/j.actatropica.2024.107125 <https://doi.org/10.1016/j.actatropica.2024.107125>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10187327/1/2024%20SALGADO.pdf