TY  - JOUR
TI  - Intranasal delivery of LaAg vaccine improves immunity of aged mice against visceral Leishmaniasis
AV  - public
Y1  - 2024/04/25/
VL  - 252
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ID  - discovery10187327
N2  - 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-? and nitrite compared to the respective unvaccinated group. Interestingly, the LaAg intranasal vaccination promoted increased production of IFN-? 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.
SN  - 0001-706X
UR  - http://dx.doi.org/10.1016/j.actatropica.2024.107125
PB  - Elsevier BV
JF  - Acta Tropica
KW  - Ageing
KW  -  Intranasal vaccine
KW  -  Leishmania amazonensis
KW  -  Visceral leishmaniasis
KW  -  antigen
A1  - Salgado, Caio Loureiro
A1  - Corea, Andrés Felipe Mendéz
A1  - Covre, Luciana Polaco
A1  - Fonseca-Martins, Alessandra Marcia
A1  - Falqueto, Aloisio
A1  - Guedes, Herbert Leonel DE Matos
A1  - Rossi-Bergmann, Bartira
A1  - Gomes, Daniel Cláudio Oliviera
ER  -