TY - JOUR
T1 - Identification and characterisation of T-cell epitopes for incorporation into dendritic cell-delivered Listeria vaccines
AU - Calderon-Gonzalez, Ricardo
AU - Raquel, Tobes
AU - Pareja, Eduardo
AU - Frande-Cabanes, Elisabet
AU - Petrovsky, Nikolai
AU - Alvarez-Dominguez, Carmen
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Dendritic cells loaded with antigenic peptides, because of their safety and robust immune stimulation, would be ideal for induction of immunity to protect against listeriosis. However, there is no currently accepted method to predict which peptides derived from the Listeria proteome might confer protection. While elution of peptides from MHC molecules after Listeria infection yields high-affinity immune-dominant epitopes, these individual epitopes did not reliably confer Listeria protection. Instead we applied bioinformatic predictions of MHC class I and II epitopes to generate antigenic peptides that were then formulated with Advax™, a novel polysaccharide particulate adjuvant able to enhance cross-presentation prior to being screened for their ability to induce protective T-cell responses. A combination of at least four intermediate strength MHC-I binding epitopes and one weak MHC-II binding epitope when expressed in a single peptide sequence and formulated with Advax adjuvant induced a potent T-cell response and high TNF-α and IL-12 production by dendritic cells resulting in robust listeriosis protection in susceptible mice. This T-cell vaccine approach might be useful for the design of vaccines to protect against listeriosis or other intracellular infections.
AB - Dendritic cells loaded with antigenic peptides, because of their safety and robust immune stimulation, would be ideal for induction of immunity to protect against listeriosis. However, there is no currently accepted method to predict which peptides derived from the Listeria proteome might confer protection. While elution of peptides from MHC molecules after Listeria infection yields high-affinity immune-dominant epitopes, these individual epitopes did not reliably confer Listeria protection. Instead we applied bioinformatic predictions of MHC class I and II epitopes to generate antigenic peptides that were then formulated with Advax™, a novel polysaccharide particulate adjuvant able to enhance cross-presentation prior to being screened for their ability to induce protective T-cell responses. A combination of at least four intermediate strength MHC-I binding epitopes and one weak MHC-II binding epitope when expressed in a single peptide sequence and formulated with Advax adjuvant induced a potent T-cell response and high TNF-α and IL-12 production by dendritic cells resulting in robust listeriosis protection in susceptible mice. This T-cell vaccine approach might be useful for the design of vaccines to protect against listeriosis or other intracellular infections.
KW - Dendritic cells
KW - Glyceraldehyde-3-phosfate-dehydrogenase
KW - Listeriolysin O
KW - Listeriosis
KW - Vaccines
UR - http://www.scopus.com/inward/record.url?scp=84940462147&partnerID=8YFLogxK
U2 - 10.1016/j.jim.2015.05.009
DO - 10.1016/j.jim.2015.05.009
M3 - Article
VL - 424
SP - 111
EP - 119
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
SN - 0022-1759
ER -