A Dendritic Cell-Targeted Vaccine Loaded with Glyceraldehyde-3-Phosphate Dehydrogenase Peptides Proposed for Individuals at High Risk of ListeriosisRicardo Calderon-Gonzalez1, Elisabet Frande-Cabanes1, Raquel Tobes2, Eduardo Pareja2, Lidia Alaez-Alvarez1 and Carmen Alvarez-Dominguez1 *
- *Corresponding Author:
- Carmen Alvarez-Dominguez
Grupo de Genómica, Proteómica y Vacunas. Instituto de Investigación Marqués de Valdecilla (IDIVAL)
Laboratorio 124, Edificio IDIVAL, Avda
Cardenal Herrera Oria, s/n. 39011 Santander, Cantabria, Spain
E-mail: [email protected]
Received date: December 15, 2014; Accepted date: January 16, 2015; Published date: January 20, 2015
Citation: Calderon-Gonzalez G, Frande-Cabanes E, Tobes R, Pareja E, Alaez-Alvarez L, et al. (2015) A Dendritic Cell-Targeted Vaccine Loaded with Glyceraldehyde-3-Phosphate Dehydrogenase Peptides Proposed for Individuals at High Risk of Listeriosis . J Vaccines Vaccin 6:266. doi: 10.4172/2157-7560.1000266
Copyright: © 2015 Calderon-Gonzalez R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Individuals at risk of Listeria infection lacked vaccines to prevent the development of severe listeriosis symptoms. Here, we identify the best epitopes from Listeria proteins GAPDH and LLO for an optimal DC vaccine candidate to protect against individuals high susceptible to listeriosis.
Methods: We vaccinated high susceptible Balb/c and low susceptible C57BL/6 mice with a single dose of DC-LLO91-99, DC-LLO189-200, DC-LLO190-201, DC-LLO189-201, DC-LLO296-304, DC-GAPDH1-15 or DC-GAPDH1-22 vaccines. CFU in spleens, predictions of DC- peptide binding to MHC-I and MHC-II and analysis of Th1 immune responses were used to assess vaccine efficiency.
Results: DC-GAPDH1-22 and DC-GAPDH1-15 vaccines with intermediate binding epitopes to MHC-I and weak binders to MHC-II, provided maximal protection in Listeria susceptible and resistant mice. DC-LLO91-99 vaccine with a strong binding epitope to MHC-I follows protection in both mice strains. DC-LLO296-304 vaccine conferred protection only in resistant mice and DC-LLO190-201, DC-LLO189-200 and DC-LLO189-201 vaccines with binding epitopes to MHC-II, lacked protection properties. Maximal protection in listeriosis correlated with increased splenic CD8α+ DC, enhanced IL-12 production and high frequencies of CD8+ and CD4+ producing IFN- T cells in both mice strains.
Discussion: Maximal protection against listeriosis in susceptible and resistant mice is only achieved with DC-GAPDH1-22 and DC-GAPDH1-15 vaccines, able to activate simultaneously CD4+ and CD8+ T cells as they include binding epitopes to both, MHC-I and MHC-II. CD8+ T cell activation seemed predominant as DC-LLO91-99 and DC-LLO296-304 vaccines that exclusively activate CD8+ T cells in both mice strains conferred significant listeriosis protection. In this regard, DC-LLO189-201, DC-LLO189-200 or DC-LLO190-201 vaccines that activated CD4+ T cells caused no protection at all. We observed that a combination of several MHC-I and at least one MHC-II binding epitopes in a single peptide provided the highest listeriosis protection.
Conclusion: DC-GAPDH1-22 and DC-GAPDH1-15 vaccines might protect against human listeriosis in high susceptible immune-compromise patients.