Highly efficient antiviral CD8+ T-cell induction by peptides coupled to the surfaces of liposomes.
In previous studies, we have demonstrated that liposomes with differential lipid components display differential adjuvant effects when antigens (Ags) are chemically coupled to their surfaces. When ovalbumin was coupled to liposomes made by using unsaturated fatty acids, it was found to be presented not only to CD4(+) T cells but also to CD8(+) T cells and induced cytotoxic T lymphocytes (CTLs) which effectively eradicated the tumor from mice. In this study, we coupled liposomes to immunodominant CTL epitope peptides derived from lymphocytic choriomeningitis virus (LCMV) and evaluated its potency as an antiviral vaccine. The intramuscular immunization of mice with the peptide-liposome conjugates along with CpG resulted in the efficient induction of antiviral CD8(+) T-cell responses which conferred complete protection against not only LCMV Armstrong but also a highly virulent mutant strain, clone 13, that establishes persistent infections in immunocompetent mice. The intranasal vaccination induced mucosal immunity effective enough to protect mice from the virus challenge via the same route. Complete protection was achieved in mice even when the Ag dose was reduced to as low as 280 ng of liposomal peptide. This form of vaccination with a single CTL epitope induced Ag-specific memory CD8(+) T cells in the absence of CD4(+) T-cell help, which could be shown by the complete protection of CD4-knockout mice in 10 weeks as well as by the analysis of recall responses. Thus, surface-linked liposomal peptide might have a potential advantage for the induction of antiviral immunity.
Takagi
Akira
A
Department of Microbiology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama 350-0495, Japan.
Matsui
Masanori
M
Ohno
Satoshi
S
Duan
Hongying
H
Moriya
Osamu
O
Kobayashi
Nobuharu
N
Oda
Hiroshi
H
Mori
Masahito
M
Kobayashi
Akiharu
A
Taneichi
Maiko
M
Uchida
Tetsuya
T
Akatsuka
Toshitaka
T
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000235:genetics; D007156:Immunologic Memory; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D015704:CD4 Antigens; C408982:CPG-oligonucleotide; D016056:Immunodominant Epitopes; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D014764:Viral Proteins; D010047:Ovalbumin
J Virol. 2002 Jun;76(11):5646-53
11991993
Vaccine. 2007 Jun 21;25(26):4914-21
17531358
J Virol. 2002 Apr;76(7):3329-37
11884558
J Virol. 1993 Dec;67(12):7340-9
7693969
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3987-91
7732018
Curr Drug Deliv. 2007 Oct;4(4):297-305
17979650
Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5189-94
18362362
J Virol. 1995 Apr;69(4):2574-82
7884908
J Exp Med. 1998 May 18;187(10):1647-57
9584143
J Virol. 2001 Nov;75(21):10421-30
11581410
Nat Immunol. 2004 Sep;5(9):927-33
15300249
J Virol. 2004 Jul;78(14):7843-5
15220461
J Immunol. 2004 Nov 15;173(10):6284-93
15528367
Nature. 1994 Jun 23;369(6482):648-52
7516038
J Immunol. 1997 Jun 1;158(11):5366-73
9164957
J Exp Med. 2008 Mar 17;205(3):533-41
18332180
J Virol. 1989 Oct;63(10):4311-6
2476571
J Exp Med. 1988 May 1;167(5):1719-24
3367096
Immunol Rev. 1998 Aug;164:29-36
9795761
Science. 2002 Sep 20;297(5589):2060-3
12242444
Science. 2003 Apr 11;300(5617):263-5
12690179
Virology. 1999 Oct 10;263(1):175-83
10544092
J Exp Med. 1998 Dec 21;188(12):2205-13
9858507
J Virol. 2004 Apr;78(8):3906-18
15047807
J Immunol. 2006 Aug 15;177(4):2324-30
16887993
J Virol. 2005 Jul;79(14):8960-8
15994790
J Exp Med. 1995 Jul 1;182(1):261-6
7540654
J Biol Chem. 1996 Jul 26;271(30):17829-36
8663374
J Exp Med. 1999 May 17;189(10):1555-64
10330434
J Clin Invest. 2006 Feb;116(2):465-75
16424939
Curr Protoc Immunol. 2001 May;Chapter 19:Unit 19.10
18432751
J Exp Med. 1998 Mar 2;187(5):685-91
9480978
J Exp Med. 2008 Mar 17;205(3):543-55
18332181
Science. 2003 Apr 11;300(5617):339-42
12690202
J Virol. 2005 Oct;79(20):12798-806
16188982
Vaccine. 2000 Aug 15;19(1):23-32
10924783
Immunity. 1996 Jan;4(1):25-36
8574849
Adv Drug Deliv Rev. 2008 May 22;60(8):915-28
18325628
Eur J Immunol. 2002 Jun;32(6):1541-9
12115636
Nature. 2003 Feb 20;421(6925):852-6
12594515
J Virol. 1999 May;73(5):4120-6
10196308
J Exp Med. 1984 Aug 1;160(2):521-40
6332167
Bioconjug Chem. 2001 May-Jun;12(3):391-5
11353537
Science. 2003 Apr 11;300(5617):337-9
12690201
Int Arch Allergy Immunol. 1999 Nov;120(3):199-208
10592465
J Virol. 1993 Jul;67(7):4372-8
8510226