Salgado, Caio Loureiro;
Corea, Andrés Felipe Mendéz;
Covre, Luciana Polaco;
Fonseca-Martins, Alessandra Marcia;
Falqueto, Aloisio;
Guedes, Herbert Leonel DE Matos;
Rossi-Bergmann, Bartira;
(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.
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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.
| Type: | Article |
|---|---|
| Title: | Intranasal delivery of LaAg vaccine improves immunity of aged mice against visceral Leishmaniasis |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.actatropica.2024.107125 |
| Publisher version: | http://dx.doi.org/10.1016/j.actatropica.2024.10712... |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Ageing, Intranasal vaccine, Leishmania amazonensis, Visceral leishmaniasis, antigen |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187327 |
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