Treatment with apo B peptide vaccines inhibits atherosclerosis in human apo B-100 transgenic mice without inducing an increase in peptide-specific antibodies.
OBJECTIVE
Autoantibodies to apolipoprotein (apo) B-100 peptides are present in human plasma and have been shown to be associated with decreased cardiovascular risk. The present study aimed to determine if apo B-100 peptide vaccines are atheroprotective in mice expressing human apo B-100 and if the effectiveness of the vaccines is influenced by the level of pre-existing peptide-specific autoantibodies.


METHODS
LDL receptor(-/-)/human apo B-100 transgenic mice were immunized with native human apo B-100 peptides p45 or p210 at 6, 9 and 11 weeks and the extent of atherosclerosis determined by en face Oil Red O staining of the aorta at 25 weeks. Autoantibody levels were determined by enzyme-linked immunosorbent assay, and RNA expression in the spleen was assessed by real time PCR.


RESULTS
Control mice had high levels of autoantibodies against p210 but only low levels against p45. Immunization with native p45 and p210 reduced atherosclerosis by 66% (P < 0.02) and 59% (P = 0.06), respectively. The atheroprotective effect of apo B peptide immunization occurred in the absence of an increase in peptide-specific IgG, but was associated with an increase in IgM recognizing native and copper-oxidized LDL.


CONCLUSIONS
Immunization with apo B peptide-based vaccines inhibits atherosclerosis in mice expressing human apo B-100 suggesting that they can interact with their target as expressed in humans. The protective effect is independent of the pre-existing level of apo B peptide autoantibodies and can occur without activating an increase in peptide-specific antibodies suggesting that atheroprotection can be mediated by cellular immune responses.
Fredrikson
G N
GN
Department of Clinical Sciences, Malmö University Hospital, Lund University, Lund, Sweden. Gunilla.Nordin_Fredrikson@med.lu.se
Björkbacka
H
H
Söderberg
I
I
Ljungcrantz
I
I
Nilsson
J
J
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics* / Q000378:metabolism; D001055:Apolipoproteins B / Q000276:immunology / Q000494:pharmacology*; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D001323:Autoantibodies / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D015870:Gene Expression; D006801:Humans; D008077:Lipoproteins, LDL; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D011973:Receptors, LDL / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D014280:Triglycerides / Q000097:blood; D022223:Vaccines, Subunit / Q000494:pharmacology*
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001323:Autoantibodies; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides; D022223:Vaccines, Subunit; C099252:oxidized low density lipoprotein; D002784:Cholesterol