Estudios fenotípicos y funcionales inducidos en células dendríticas humanas por vacunas de origen bacteriano

  1. Cirauqui Armendáriz, Cristina
Dirigée par:
  1. Oscar Palomares Gracia Directeur

Université de défendre: Universidad Complutense de Madrid

Fecha de defensa: 14 juin 2017

Jury:
  1. María José Feito Castellano President
  2. Silvia Ortega Gutiérrez Secrétaire
  3. José Luis Subiza Garrido-Lestache Rapporteur
  4. Javier Cuesta Herranz Rapporteur
  5. Alberto Lázaro Fernández Rapporteur
Département:
  1. Bioquímica y Biología Molecular

Type: Thèses

Résumé

Recurrent respiratory tract infections (RRTIs) and recurrent urinary tract infections (RUTIs) are the most common infections worldwide with a significant mortality rate. RRTIs and RUTIs represent a major health problem with a very high socioeconomic impact. Up to date, antibiotics remain the mainstay of treatment and they show clinical efficacy in many cases. However, RRTIs and RUTIs require repeated and prolonged antibiotic cycles, further increasing the risk to develop antibiotic resistances. Other negative factors associated to the overuse of antibiotics include deleterious effects for the normal microbiome, which favour pathogen invasion and subsequent bacterial and fungal superinfections. Therefore, the last reports from the World Health Organization (WHO) stated that there is an urgent need for new alternative approaches to antibiotics for the prevention and treatment of RRTIs and RUTIs able to overcome the main drawbacks associated to the overuse of antibiotics. At this regard, mucosal bacterial vaccines have demonstrated efficacy in the prevention and treatment of recurrent infections as they can potentiate immune responses both at the site of administration as well as in distant tissues, thus contributing to avoid the pathogen colonization and infection at their natural site of entrance. Recent studies showed that sublingual immunizations with MV130 (Bactek®) and MV140 (Uromune®), polybacterial preparations (PBPs) based on whole inactivated components from Inmunotek S.L., significantly reduced the infection rates in patients suffering from RRTIs and RUTIs, respectively. MV130 is composed of different proportions of whole heat-inactivated Gram-positive and –negative bacteria often present in the respiratory tract and causing the majority of upper and lower respiratory infections in Europe (90% Gram-positive: 60% Streptococcus pneumoniae, 15% Staphylococcus aureus, 15% Staphylococcus epidermidis; 10% Gram-negative: 4% Klebsiella pneumoniae, 3% Moraxella catarrhalis and 3% Haemophilus influenzae). MV140 is composed of different proportions of whole heat-inactivated Gram-positive and –negative bacteria often causing urinary infections (75% Gram-negative bacteria: 25% Escherichia coli, 25% Proteus vulgaris, 25% Klebsiella pneumoniae; and 25% Gram-positive bacteria: Enterococcus faecalis)...