Vaccines & Vaccination

Biography

Biography: Carmen Alvarez-Dominguez

Abstract

Susceptible and resistant mice to listeriosis are convenient models to examine vaccines efficiency since they mimic human diversity. Dendritic cells (DC) vaccines loaded with immunogeneic peptides are powerful tools for the vaccination against intracellular bacteria. To produce a vaccine against the human bacterial pathogen, Listeria monocytogenes, we assessed DC loaded with immunogenic listeriolysin O (LLO) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) peptides. Our approach consisted on examining DC-LLO or DC-GAPDH vaccines coupled with peptides with different binding capacities to MHC molecules in susceptible or resistant mice. DC-GAPDH1-22 vaccines that contained weak binding sequences to IAb and IAd MHC class II molecules and medium binding sequences to H-2Kb and H-2Kd MHC class I molecules, provided the best protection to listeriosis in susceptible and resistant mice. DC-LLO91-99 vaccines loaded with a strong peptide binder to H-2Kd but weak binder to H-2Kb MHC class I molecules, conferred better protection than DC-LLO296-304 vaccines loaded exclusively with a strong peptide binder to H-2Kb. DC-LLO190-201, DC-LLO189-200 and DC-LLO189-201 vaccines loaded exclusively with weak peptide binders to IAb and IAd MHC class II molecules, respectively, presented no significant protection. Enhanced protection in listeriosis correlated with increased splenic CD8+ DC, enhanced IL-12 and expansion of Listeria antigen specific CD8+ and CD4+ T cells producing IFN-. DC-GAPDH1-22 vaccines that combine any type of CD8+ epitopes and CD4+ weak binder epitopes conferred higher protection to listeriosis in susceptible and resistant mice, than DC-LLO91-99 or DC-LLO296-304 vaccines that include exclusively CD8+ epitopes. DC-GAPDH1-22 vaccines could be an effective vaccine for prophylactic protection against human listeriosis in susceptible and resistant individuals.