Construction and immunological evaluation of multivalent hepatitis B virus (HBV) core virus-like particles carrying HBV and HCV epitopes.
A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBcDelta protein (N-terminal aa 1 to 144 of full-length HBc) were produced in Escherichia coli cells and examined for their antigenicity and immunogenicity. The presence of two different foreign epitopes within the HBc molecule did not interfere with its VLP-forming ability, with the HBV pre-S1 epitope exposed on the surface and the HCV core epitope buried within the VLPs. After immunization of BALB/c mice, specific T-cell activation by both foreign epitopes and a high-titer antibody response against the pre-S1 epitope were found, whereas an antibody response against the HBc carrier was notably suppressed. Both inserted epitopes also induced a specific cytotoxic-T-lymphocyte (CTL) response, as shown by the gamma interferon (IFN-gamma) production profile.
Sominskaya
Irina
I
Latvian Biomedical Research and Study Centre, Ratsupites Street 1, LV-1067 Riga, Latvia. irina@biomed.lu.lv
Skrastina
Dace
D
Dislers
Andris
A
Vasiljev
Denis
D
Mihailova
Marija
M
Ose
Velta
V
Dreilina
Dzidra
D
Pumpens
Paul
P
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016174:Hepacivirus / Q000276:immunology* / Q000378:metabolism; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology* / Q000378:metabolism; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D000939:Epitopes; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014761:Viral Hepatitis Vaccines
Clin Immunol. 2004 Apr;111(1):22-7
15093548
World J Gastroenterol. 2005 Jan 28;11(4):492-7
15641132
J Virol. 1989 May;63(5):1981-8
2649690
J Med Virol. 1994 May;43(1):62-8
7521899
Med Microbiol Immunol. 1992;181(4):215-26
1279369
J Clin Invest. 1989 Oct;84(4):1314-9
2529268
J Virol. 1995 Sep;69(9):5859-63
7637033
J Immunol. 2002 Mar 15;168(6):2880-6
11884458
J Immunol Methods. 2002 Feb 1;260(1-2):251-61
11792393
Protein Expr Purif. 2006 Nov;50(1):43-8
16889980
Am J Med. 1999 Dec 27;107(6B):21S-26S
10653451
Intervirology. 1999;42(1):51-6
10393504
J Virol. 1992 Jan;66(1):106-14
1370083
J Virol. 1995 Apr;69(4):2462-70
7884894
J Immunol. 2004 Feb 1;172(3):1777-85
14734761
Mol Immunol. 1993 Feb;30(3):221-31
7679466
Curr Stud Hematol Blood Transfus. 1994;(61):1-11
7956324
Genet Vaccines Ther. 2009 Jun 08;7:7
19505299
Intervirology. 2000;43(4-6):218-26
11251377
J Gen Virol. 2004 Sep;85(Pt 9):2665-2670
15302960
Mol Cell. 1999 Jun;3(6):771-80
10394365
Cell. 1994 Jun 17;77(6):943-50
8004680
J Virol. 2007 Jun;81(11):5841-9
17376925
Vaccine. 2006 May 15;24(20):4369-77
16574285
IUBMB Life. 2000 Dec;50(6):379-84
11327311
J Exp Med. 1988 Jul 1;168(1):293-306
2456369
Dokl Akad Nauk SSSR. 1981;260(4):1022-4
7030681
Biol Chem. 1999 Mar;380(3):315-24
10223334
World J Gastroenterol. 2006 Dec 28;12(48):7774-8
17203519
Vaccine. 2008 Apr 7;26(16):1972-81
18343539
Virology. 1991 Feb;180(2):483-91
1703368
Hepatology. 1996 Jul;24(1):14-20
8707253
Intervirology. 2001;44(2-3):98-114
11509871
Vaccine. 1986 Mar;4(1):35-7
2421497
Nature. 1987 Nov 26-Dec 2;330(6146):381-4
2446137
Vaccine. 2004 Jan 2;22(3-4):439-46
14670326
J Immunol. 2002 May 15;168(10):4951-9
11994446
Anal Biochem. 2004 Sep 1;332(1):153-9
15301960