A novel staphylococcal enterotoxin B subunit vaccine candidate elicits protective immune response in a mouse model

被引:15
作者
Choi, Jun Young [1 ]
Shin, Sungho [3 ]
Kim, Na Young [4 ]
Son, Woo Sung [5 ]
Kang, Tae Jin [6 ]
Song, Dong Hyun [7 ]
Yu, Chi Ho [7 ]
Hur, Gyeung Haeng [7 ]
Jeong, Seong Tae [7 ]
Shin, Young Kee [1 ,2 ,3 ]
机构
[1] Seoul Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Seoul 08826, South Korea
[2] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Mol Med & Biopharmaceut Sci, Seoul, South Korea
[3] Seoul Natl Univ, BioMAX N Bio, Seoul, South Korea
[4] ABION Inc, R&D Ctr, Seoul, South Korea
[5] CHA Univ, Dept Pharm, Coll Pharm, Pocheon Si, South Korea
[6] Sahmyook Univ, Coll Pharm, Seoul, South Korea
[7] Agcy Def Dev, Seoul, Daejeon, South Korea
关键词
Mutation; Recombinant vaccine; Staphylococcal enterotoxin B; Vaccine candidates; STRUCTURAL BASIS; SUPERANTIGEN; IMMUNIZATION; MUTANTS; MUCOSAL; COMPLEX; TOXINS;
D O I
10.1016/j.toxicon.2017.03.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Staphylococcal enterotoxin B (SEB), produced by the gram-positive bacterium Staphylococcus aureus, is responsible for food poisoning and toxic shock syndrome, and is considered a potential bioterrorism agent. Unfortunately, still now no approved vaccines are available against SEB. In this study, we constructed a series of nontoxic SEB mutants (mSEBs) and examined whether these mSEBs provide protective immunity against SEB challenge. These mSEB vaccine candidates did not demonstrate superantigen activity in mouse splenocyte cultures. Immunization with the vaccine candidates triggered the production of IgG-antibodies with neutralizing activity. In addition, increased production of IgG1 and IgG3 was observed after immunization, which signifies both Thl- and Th2-induced immune responses. Among the vaccine candidates tested, S9, a double mutant (N23A and Y90A) and S19, a quadruple mutant (N23A, Y90A, R110A, and F177A), demonstrated complete protection against a lethal SEB challenge. Altogether, our results strongly suggest that these mSEBs could be an effective recombinant SEB vaccine candidates for further/future preclinical and clinical studies. (C) 2017 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:68 / 77
页数:10
相关论文
共 33 条
[1]  
Ahanotu E., 2006, Appl. Biosaf, V11, P120, DOI [10.1177/153567600601100303, DOI 10.1177/153567600601100303]
[2]   Generation of protective immunity by inactivated recombinant staphylococcal enterotoxin B vaccine in nonhuman primates and identification of correlates of immunity [J].
Boles, JW ;
Pitt, MLM ;
LeClaire, RD ;
Gibbs, PH ;
Torres, E ;
Dyas, B ;
Ulrich, RG ;
Bavari, S .
CLINICAL IMMUNOLOGY, 2003, 108 (01) :51-59
[3]   The evolving field of biodefence: Therapeutic developments and diagnostics [J].
Burnett, JC ;
Henchal, EA ;
Schmaljohn, AL ;
Bavari, S .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (04) :281-297
[4]   Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax [J].
Chen, Wilbur H. ;
Pasetti, Marcela F. ;
Adhikari, Rajan P. ;
Baughman, Holly ;
Douglas, Robin ;
El-Khorazaty, Jill ;
Greenberg, Nancy ;
Holtsberg, Frederick W. ;
Liao, Grant C. ;
Reymann, Mardi K. ;
Wang, Xiaolin ;
Warfield, Kelly L. ;
Aman, M. Javad .
CLINICAL AND VACCINE IMMUNOLOGY, 2016, 23 (12) :918-925
[5]   Production and purification of a recombinant staphylococcal enterotoxin B vaccine candidate expressed in Escherichia coli [J].
Coffman, JD ;
Zhu, JW ;
Roach, JM ;
Bavari, S ;
Ulrich, RG ;
Giardina, SL .
PROTEIN EXPRESSION AND PURIFICATION, 2002, 24 (02) :302-312
[6]   The bacterial superantigen and superantigen-like proteins [J].
Fraser, John D. ;
Proft, Thomas .
IMMUNOLOGICAL REVIEWS, 2008, 225 :226-243
[7]  
Fraser John D., 2007, V93, P1, DOI 10.1159/000100851
[8]   INTERLEUKIN-12 PROFOUNDLY UP-REGULATES THE SYNTHESIS OF ANTIGEN-SPECIFIC COMPLEMENT-FIXING IGG2A, IGG2B AND IGG3 ANTIBODY SUBCLASSES IN-VIVO [J].
GERMANN, T ;
BONGARTZ, M ;
DLUGONSKA, H ;
HESS, H ;
SCHMITT, E ;
KOLBE, L ;
KOLSCH, E ;
PODLASKI, FJ ;
GATELY, MK ;
RUDE, E .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (03) :823-829
[9]   BACTERIAL TOXINS - A TABLE OF LETHAL AMOUNTS [J].
GILL, DM .
MICROBIOLOGICAL REVIEWS, 1982, 46 (01) :86-94
[10]   A mutant of staphylococcal enterotoxin C devoid of bacterial superantigenic activity elicits a Th2 immune response for protection against Staphylococcus aureus infection [J].
Hu, DL ;
Cui, JC ;
Omoe, K ;
Sashinami, H ;
Yokomizo, Y ;
Shinagawa, K ;
Nakane, A .
INFECTION AND IMMUNITY, 2005, 73 (01) :174-180