Log in

The preparation and therapeutic roles of scFv-Fc antibody against Staphylococcus aureus infection to control bovine mastitis

  • Biotechnological products and process engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Staphylococcus aureus–induced bovine mastitis causes significant losses to the dairy industry and available vaccines do not confer adequate protection. As a more attractive alternative, we propose the use of antibody (Ab) therapy. In our previous study, we constructed a bovine single-chain variable fragment (scFv) Ab phage display and successfully obtained scFvs that bound to S. aureus antigens with high affinity. Here, we describe a novel Ab against S. aureus (scFv-Fc Ab). To construct the scFv-Fc Ab, the scFv Ab was genetically fused to the Fc fragment of a bovine IgG1 Ab. Western blot analysis showed that the bovine scFvs-Fc Abs were successfully expressed with horseradish peroxidase–conjugated goat-anti-bovine IgG (Fc) Ab in Escherichia coli cells. The purified bovine scFvs-Fc Abs had good binding activity to S. aureus and effectively inhibited the bacterial growth in culture medium and bovine scFvs-Fc Abs enhanced phagocytosis of S. aureus by neutrophils isolated from peripheral blood in a dose-dependent manner. In the experiment of bovine scFvs-Fc Abs for the treatment of S. aureus–induced bovine mastitis, the total effective percentage reached 82% (9/11). These novel bovine scFvs-Fc Abs may be useful as therapeutic candidates for the prevention and treatment of S. aureus–induced bovine mastitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Barkema HW, Schukken YH, Zadoks RN (2006) Invited review: the role of cow, pathogen, and treatment regimen in the therapeutic success of bovine Staphylococcus aureus mastitis. J Dairy Sci 89:1877–1895

    Article  CAS  PubMed  Google Scholar 

  • Bax HJ, Josephs DH, Pellizzari G, Spicer JF, Montes A, Karagiannis SN (2016) Therapeutic targets and new directions for antibodies developed for ovarian cancer. MAbs 8:1437–1455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, Lee T, Pope SH, Riordan GS, Whitlow M (1988) Single-chain antigen-binding proteins. Science 242:423–426

    Article  CAS  PubMed  Google Scholar 

  • Bradley AJ (2002) Bovine mastitis: an evolving disease. Vet J 164:116–128

    Article  CAS  PubMed  Google Scholar 

  • Brouillette E, Malouin F (2005) The pathogenesis and control of Staphylococcus aureus-induced mastitis: study models in the mouse. Microbes Infect 7:560–568

    Article  PubMed  Google Scholar 

  • Feige MJ, Hendershot LM, Buchner J (2009) How antibodies fold. Trends Biochem Sci 35:189–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furth PA, Shamay A, Wall R, Hennighausen L (1992) Gene transfer into somatic tissues by jet injection. Anal Biochem 205:365–368

    Article  CAS  PubMed  Google Scholar 

  • Harris JM, Chess RB (2003) Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2:214–221

    Article  CAS  PubMed  Google Scholar 

  • Jazayeri JA, Carroll GJ (2008) Fc-based cytokines: prospects for engineering superior therapeutics. Biodrugs 22:11–26

    Article  CAS  PubMed  Google Scholar 

  • Kaneko E, Niwa R (2011) Optimizing therapeutic antibody function: progress with Fc domain engineering. BioDrugs 25:1–11

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Sim DW, Park DS, Jung TG, Lee S, Oh T, Ha JR, Seok SH, Seo MD, Kang HC, Kim YP, Won HS (2016) Bacterial production and structure-functional validation of a recombinant antigen-binding fragment (Fab) of an anti-cancer therapeutic antibody targeting epidermal growth factor receptor. Appl Microbiol Biotechnol 100:10521–10529

    Article  CAS  PubMed  Google Scholar 

  • Klinman DM, Yamshchikov G, Ishigatsubo Y (1997) Contribution of CpG motifs to the immunogenicity of DNA vaccines. J Immunol 158:3635–3639

    CAS  PubMed  Google Scholar 

  • Kontermann RE (2009) Strategies to extend plasma half-lives of recombinant antibodies. Biodrugs 23:93–109

    Article  CAS  PubMed  Google Scholar 

  • McAuley A, Jacob J, Kolvenbach CG, Westland K, Lee HJ, Brych SR, Rehder D, Kleemann GR, Brems DN, Matsumura M (2008) Contributions of a disulfide bond to the structure, stability, and dimerization of human IgG1 antibody CH3 Domain. Protein Sci 17:95–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Middleton JR (2008) Staphylococcus aureus antigens and challenges in vaccine development. Expert Rev Vaccines 7:805–815

    Article  CAS  PubMed  Google Scholar 

  • Middleton JR, Hardin D, Steevens B, Randle R, Tyler JW (2004) Use of somatic cell counts and California mastitis test results from individual quarter milk samples to detect subclinical intramammary infection in dairy cattle from a herd with a high bulk tank somatic cell count. J Ame Vet Med Assoc 224:419–423

    Article  Google Scholar 

  • Nordhaug ML, Nesse LL, Norcross NL, Gudding R (1994) A field trial with an experimental vaccine against staphylococcus aureus mastitis in callte: 2. Antibody response. J Dairy Sci 77:1276–1284

    Article  CAS  PubMed  Google Scholar 

  • Ono K, Kamihira M, Kuga Y, Matsumoto H, Hotta A, Itoh T, Nishijima K, Nakamura N, Matsuda H, Lijima S (2003) Production of anti-prion scFv-Fc fusion proteins by recombinant animal cells. J Biosci Bioeng 95:231–238

    Article  CAS  PubMed  Google Scholar 

  • Pennini ME, De Marco A, Pelletier M, Bonnell J, Cvitkovic R, Beltramello M, Cameroni E, Bianchi S, Zatta F, Zhao W, **ao XD, Camara MM, DiGiandomenico A, Semenova E, Lanzavecchia A, Warrener P, Suzich J, Wang Q, Corti D, Stover CK (2017) Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumonia. Nat Commun 8:1991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rasetti-Escargueil C, Avril A, Chahboun S, Tierney R, Bak N, Miethe S, Mazuet C, Popoff MR, Thulier P, Hust M, Pelat T, Sesardic D (2015) Development of human-like scFv-Fc antibodies neutralizing Botulinum toxin serotype B. MAbs 7:1161–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roth JA, Kaeberle ML (1981) Evaluation of bovine polymorphonuclear leukocyte function. Vet Immunol Immunopathol 2:157–174

    Article  CAS  PubMed  Google Scholar 

  • Shinefield HR, Black S (2005) Prevention of Staphylococcus aureus infections: advances in vaccine development. Expert Rev Vaccines 4:669–676

    Article  CAS  PubMed  Google Scholar 

  • Sokolowska-Wedzina A, Chodaczek G, Chudzian J, Borek A, Zakrzewska M, Otlewski J (2017) High-affinity internalizing human scFv-Fc antibody for targeting FGFR1-overexpressing lung cancer. Mol Cancer Res 15:1040–1050

    Article  CAS  PubMed  Google Scholar 

  • Stevens MG, Kehrli ME Jr, Canning PC (1991) A colorimetric assay for quantitating bovine neutrophil bactericidal activity. Vet Immunol Immunopathol 28:45–56

    Article  CAS  PubMed  Google Scholar 

  • Symons DBA, Clarkson CA, Beale D (1989) Structure of bovine immunlglobulin constant region heavy chain gamma 1 and gamma 2 genes. Mol Immunol 26:841–850

    Article  CAS  PubMed  Google Scholar 

  • Tan GY, Bai LQ, Zhong JJ (2013) Exogenous 1,4-butyrolactone stimulates A-factor-like cascade and validamycin biosynthesis in Streptomyces hygroscopicus 5008. Biotechnol Bioeng 110:2984–2993

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Zhang Y, Li BQ, Zhu JG (2015) Construction of scFv that bind both fibronectin-binding protein A and clum** factor A of Stapylococcus aureus. Res Vet Sci 100:109–114

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Zhang Y, Zhu JG (2016) Anti-Staphylococcus aureus single-chain variable region fragments provide protection against mastitis in mice. Appl Microbiol Biotechnol 100:2153–2162

    Article  CAS  PubMed  Google Scholar 

  • Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    Article  CAS  Google Scholar 

  • Yokota T, Milenic DE, Whitlow M, Schlom J (1992) Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res 52:3402–3408

    CAS  PubMed  Google Scholar 

  • Zhen YH, ** LJ, Guo J, Li XY, Li Z, Fang R, Xu YP (2008) Characterization of specific egg yolk immunoglobulin (IgY) against mastitis-causing staphylococcus aureus. J Appl Microbiol 105:1529–1535

    Article  CAS  PubMed  Google Scholar 

  • Zwick MB, Wang M, Poignard P, Stienler G, Katinger H, Burton DR, Parren PW (2001) Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies. J Virol 75:12198–12208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by the National Key Research and Development Program of China (Grant Number: 2018YFD0501600).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jianguo Zhu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was conducted in accordance with all applicable international, national, and institutional guidelines for the care and use of animals.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 261 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, M., Wang, T., Guan, Y. et al. The preparation and therapeutic roles of scFv-Fc antibody against Staphylococcus aureus infection to control bovine mastitis. Appl Microbiol Biotechnol 103, 1703–1712 (2019). https://doi.org/10.1007/s00253-018-9548-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-018-9548-6

Keywords

Navigation