@article{10902/13461,
year = {2017},
month = {7},
url = {http://hdl.handle.net/10902/13461},
abstract = {Clinical cases of neonatal listeriosis are associated with brain disease and fetal loss due to complications in early or late pregnancy, which suggests that microglial function is altered. This is believed to be the first study to link microglial apoptosis with neonatal listeriosis and listeriosis-associated brain disease, and to propose a new nanovaccine formulation that reverses all effects of listeriosis and confers Listeria monocytogenes (LM)-specific immunity. We examined clinical cases of neonatal listeriosis in 2013-2015 and defined two useful prognostic immune biomarkers to design listeriosis vaccines: high anti-GAPDH1-22 titres and tumor necrosis factor (TNF)/interleukin (IL)-6 ratios. Therefore, we developed a nanovaccine with gold glyco-nanoparticles conjugated to LM peptide 1-22 of GAPDH (Lmo2459), GNP-GAPDH1-22 nanovaccinesformulated with a pro-inflammatory Toll-like receptor 2/4-targeted adjuvant. Neonates born to non-vaccinated pregnant mice with listeriosis, showed brain and vascular diseases and significant microglial dysfunction by induction of TNF-?-mediated apoptosis. This programmed TNF-mediated suicide explains LM dissemination in brains and livers and blocks production of early pro-inflammatory cytokines such as IL-1? and interferon-?/?. In contrast, neonates born to GNP-GAPDH1-22-vaccinated mothers before LM infection, did not develop listeriosis or brain diseases and had functional microglia. In nanovaccinated mothers, immune responses shifted towards Th1/IL-12 pro-inflammatory cytokine profiles and high production of anti-GAPDH1-22 antibodies, suggesting good induction of LM-specific memory.},
publisher = {Impact Journals},
publisher = {Oncotarget. 2017 Jul 20;8(33):53916-53934},
title = {GNP-GAPDH1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination},
author = {Calderón González, Ricardo and Frande Cabanes, Elisabet and Terán Navarro, Héctor and Marimon, José María and Freire Salinas, Javier and Salcines Cuevas, David and Fariñas Álvarez, María del Carmen and González Rico, Claudia and Marradi, Marco and Garcia, Isabel and Alkorta Gurrutxaga, Mirian and San Nicolás Gómez, Aida and Castañeda Sampedro, Ana and Yáñez Díaz, Sonsoles Juana and Penades, Soledad and Punzon, Carmen and Gómez Román, José Javier and Rivera Herrero, Fernando and Fresno, Manuel and Álvarez Domínguez, Carmen},
}