Immunization with plasmid DNA encoding the integral membrane protein, Sm23, elicits a protective immune response against schistosome infection in mice

被引:63
作者
Da'dara, AA [1 ]
Skelly, PJ [1 ]
Wang, MM [1 ]
Harn, DA [1 ]
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
关键词
Sm23; DNA vaccine; Schistosoma mansoni;
D O I
10.1016/S0264-410X(01)00374-7
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Schistosomes are helminth parasites infecting at least 200 million people worldwide. In this study. we evaluated the feasibility of using a nucleic acid vaccine to induce protective immune responses to the Schistosoma mansoni integral membrane protein Sm23. C57BL/6 mice were immunized by intramuscular injection in three separate vaccination trials. ELISA and Western Blot analyses indicated that mice immunized with a DNA plasmid construct encoding Sm23 (Sm23-pcDNA) generated specific IgG for Sm23. while sera from mice immunized with the control pcDNA plasmid did not. The vaccine elicited IgG(2a), and IgG(1) antibody isotypes. We also tested the adjuvant activity of IL-12 and IL-4 on humoral responses to Sm23. Co-immunization with plasmid encoding IL-12 did not affect the level of anti-Sm23 IgG(2a), but did reduce the IgG(1) level. In contrast, co-injection with a plasmid encoding IL-4 significantly reduced the level of anti-Sm23 IgG(2a), while the level of IgG(1) was largely unchanged. Importantly. the Sm23-pcDNA vaccine provided statistically significant levels of protection against challenge infection (21-44%. P < 0.001-0.02). Co-administration of plasmids encoding either IL-12 or IL-4 did not significantly enhance this protective effect. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:359 / 369
页数:11
相关论文
共 48 条
[31]   PURIFICATION AND IMMUNOCHEMICAL CHARACTERIZATION OF A 22 KILODALTON SURFACE-ANTIGEN FROM SCHISTOSOMA-MANSONI [J].
OLIGINO, LD ;
PERCY, AJ ;
HARN, DA .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1988, 28 (02) :95-103
[32]   Cytokines and costimulatory molecules as genetic adjuvants [J].
Pasquini, S ;
Xiang, Z ;
Wang, Y ;
He, Z ;
Deng, H ;
BlaszczykThurin, M ;
Ertl, HCJ .
IMMUNOLOGY AND CELL BIOLOGY, 1997, 75 (04) :397-401
[33]  
Radford KJ, 1997, J IMMUNOL, V158, P3353
[34]   Genetic vaccination strategies for enhanced cellular, humoral and mucosal immunity [J].
Ramsay, AJ ;
Kent, SJ ;
Strugnell, RA ;
Suhrbier, A ;
Thomson, SA ;
Ramshaw, IA .
IMMUNOLOGICAL REVIEWS, 1999, 171 :27-44
[35]  
REYNOLDS SR, 1992, J IMMUNOL, V149, P3995
[36]  
RICHTER D, 1993, J IMMUNOL, V151, P256
[37]   TRICINE SODIUM DODECYL-SULFATE POLYACRYLAMIDE-GEL ELECTROPHORESIS FOR THE SEPARATION OF PROTEINS IN THE RANGE FROM 1-KDA TO 100-KDA [J].
SCHAGGER, H ;
VONJAGOW, G .
ANALYTICAL BIOCHEMISTRY, 1987, 166 (02) :368-379
[38]  
Scott P, 1997, Semin Immunol, V9, P285, DOI 10.1006/smim.1997.0084
[39]  
Sin JI, 1999, J IMMUNOL, V162, P2912
[40]   In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model [J].
Sin, JI ;
Kim, JJ ;
Boyer, JD ;
Ciccarelli, RB ;
Higgins, TJ ;
Weiner, DB .
JOURNAL OF VIROLOGY, 1999, 73 (01) :501-509