Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice.
Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine-phosphate-guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design.
Lu
Baojing
B
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Science, Wuhan.
Huang
Yi
Y
Huang
Li
L
Li
Bao
B
Zheng
Zhenhua
Z
Chen
Ze
Z
Chen
Jianjun
J
Hu
Qinxue
Q
Wang
Hanzhong
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016367:Baculoviridae; D004195:Disease Models, Animal; D005260:Female; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000493:pharmacokinetics*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology / Q000493:pharmacokinetics*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D014765:Viral Vaccines
Proteomics. 2004 Feb;4(2):492-504
14760722
Clin Vaccine Immunol. 2007 Jul;14(7):894-901
17494640
J Immunol. 1998 Nov 1;161(9):4463-6
9794366
J Virol. 1998 Oct;72(10):8220-9
9733865
J Immunol. 1998 Jan 15;160(2):870-6
9551923
Methods. 2006 Sep;40(1):60-5
16997714
Cell. 1989 Oct 6;59(1):103-12
2676191
Biochem Biophys Res Commun. 2004 Jun 11;318(4):833-8
15147946
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7956-61
12060741
Vaccine. 2008 Aug 19;26 Suppl 10:K53-61
18847557
Vaccine. 1998 Jul;16(11-12):1216-24
9682382
J Immunol. 2001 Mar 1;166(5):3451-7
11207303
Viral Immunol. 2008 Mar;21(1):27-37
18355120
Science. 2003 May 30;300(5624):1394-9
12730500
Vaccine. 2003 Sep 8;21(25-26):3885-900
12922123
J Biol Chem. 2005 Aug 19;280(33):29588-95
15980414
Nature. 1995 Apr 6;374(6522):546-9
7700380
Immunobiology. 1992 Feb;184(2-3):157-79
1587541
J Virol. 2005 Sep;79(18):11638-46
16140741
Proc Natl Acad Sci U S A. 1997 May 13;94(10):5267-72
9144226
Vaccine. 2006 Jan 30;24(5):652-61
16214268
Eur J Immunol. 2008 Jan;38(1):114-26
18081037
Arch Virol. 2005 Feb;150(2):341-9
15578236
N Engl J Med. 2003 May 15;348(20):1967-76
12690091
PLoS One. 2008 Jul 16;3(7):e2685
18628832
Science. 2002 Apr 12;296(5566):356-9
11896235
Immunology. 2007 Dec;122(4):496-502
17680799
FEBS Lett. 2004 Oct 8;576(1-2):174-8
15474033
Virology. 2009 Jun 5;388(2):344-53
19409593
J Virol. 2005 Nov;79(22):13915-23
16254327
Vaccine. 2009 Apr 14;27(17):2326-34
19428847
Nature. 2004 Apr 1;428(6982):561-4
15024391
J Biotechnol. 2005 Oct 17;120(1):72-82
16023241
Science. 2003 May 30;300(5624):1399-404
12730501
Proc Natl Acad Sci U S A. 2003 May 27;100(11):6753-8
12748380
Lancet. 2003 Apr 19;361(9366):1319-25
12711465
J Virol. 2003 Mar;77(6):3615-23
12610137
J Virol. 2004 Jul;78(13):6995-7003
15194776
Cell Immunol. 1998 Nov 25;190(1):77-82
9826449