DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination biases towards T helper 1 responses and enhances protection against Leishmania major infection in mice.
Successful resolution of infections by intracellular pathogens requires gamma interferon (IFN-gamma). DNA vaccines promote T helper 1 (Th1) responses by triggering interleukin-12 (IL-12) release by dendritic cells (DC) through Toll-like receptor 9 (TLR9). In humans TLR9 is restricted to plasmacytoid DC. Here we show that DNA-Salmonella enterica serovar Typhimurium primer-booster vaccination, which provides alternative ligands to bind TLR4 on myeloid DC, strongly biases towards Th1 responses compared to vaccination with DNA alone. This results in higher immunoglobulin G2a (IgG2a) responses compared to IgG1 responses, higher IFN-gamma responses compared to IL-10 CD4(+)-T-cell responses, and enhanced protection against Leishmania major infection in susceptible BALB/c mice.
Cambridge Institute for Medical Research, and Department of Medicine, School of Clinical Medicine, University of Cambridge, United Kingdom.
Uta G
UG
Lange
Pietro
P
Mastroeni
Jenefer M
JM
Blackwell
Carmel B
CB
Stober
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007114:Immunization; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics*; D013744:Tetanus Toxin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D013744:Tetanus Toxin; D019444:Vaccines, DNA; C040635:tetanus toxin fragment C; C093139:LACK antigen, Leishmania; D007371:Interferon-gamma