Atheroprotective immunization with MDA-modified apo B-100 peptide sequences is associated with activation of Th2 specific antibody expression.
OBJECTIVE
The objective of this study was to evaluate if immunization with MDA-modified human apo B-100 fragments is associated with a shift in the Th1/Th2 balance.


RESULTS
Apo E deficient mice were immunized with one of the peptides (P45; amino acids 688-707, P74; amino acids 1123-1142 or P240; amino acids 3613-3632) at 6, 9 and 11 weeks of age and compared to controls given carrier alone. Immunization with P45 and P74 reduced atherosclerosis in the aorta of 25-week-old mice by 48% (p=0.02) and 31% (p=0.06) and macrophage content in atherosclerotic plaques by 33% (p=0.02) and 39% (p=0.02), respectively. The levels of Th2-specific IgG1 against each peptide increased more than 50-fold in response to immunization, whereas the levels of specific IgM and Th1-associated IgG2a were only marginally affected. However, there was an increase in the plaque expression of both Th1 and Th2 cytokines as assessed by real time PCR. Immunization with P240, a non-homologous peptide used as control, induced a 10-fold increase of specific IgG1 but did not influence atherosclerosis or plaque content.


CONCLUSIONS
Immunization with MDA apo B-100 fragments induce a shift from Th1 to a Th2 specific oxidized LDL antibody expression, but without a concomitant downregulation of plaque IFN-gamma expression.
Fredrikson
Gunilla Nordin
GN
Department of Medicine, Lund University, Wallenberg Labortatory 1st floor, Malmö University Hospital, 205 02 Malmö, Sweden. gunilla.nordin_fredrikson@medforsk.mas.lu.se
Andersson
Linda
L
Söderberg
Ingrid
I
Dimayuga
Paul
P
Chyu
Kuang-Yuh
KY
Shah
Prediman K
PK
Nilsson
Jan
J
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry / Q000276:immunology*; D001057:Apolipoproteins E / Q000172:deficiency; D001161:Arteriosclerosis / Q000517:prevention & control*; D006801:Humans; D007114:Immunization; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D000906:Antibodies; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D010455:Peptides; D022223:Vaccines, Subunit; C099252:oxidized low density lipoprotein