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GNP-GAPDH1-22 nanovaccines prevent neonatal listeriosis by blocking microglial apoptosis and bacterial dissemination

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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Oncotarget. 2017 Jul 20;8(33):53916-53934

Editorial: Impact Journals

 Fecha de publicación: 01/07/2017

Nº de páginas: 19

Tipo de publicación: Artículo de Revista

 DOI: 10.18632/oncotarget.19405

ISSN: 1949-2553

Proyecto español: SAF2012-34203 ; RD12/0018/0004 ; SAF2013-42850-R ; CTQ2011-27268

Autores/as

RICARDO CALDERON GONZALEZ

ELISABET FRANDE CABANES

HECTOR TERAN NAVARRO

MARIMON, JOSÉ MARÍA

JAVIER FREIRE SALINAS

SALCINES CUEVAS, DAVID

GONZÁLEZ RICO, CLAUDIA

MARRADI, MARCO

GARCIA, ISABEL

ALKORTA GURRUTXAGA, MIRIAN

AIDA SAN NICOLAS GOMEZ

CASTAÑEDA SAMPEDRO, ANA

PENADES, SOLEDAD

PUNZON, CARMEN

FERNANDO RIVERA HERRERO

FRESNO, MANUEL

CARMEN ALVAREZ DOMINGUEZ