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Piri-Gavgani, Somayeh, Ghanei, Mostafa, Fateh, Abolfazl, Siadat, Seyed Davar, Nematollahi, Leila, Rahimi-Jamnani, Fatemeh. (1401). Identification of two neutralizing human single-chain variable fragment antibodies targeting Staphylococcus aureus alpha-hemolysin. , 25(10), 1207-1214. doi: 10.22038/ijbms.2022.64103.14253
Somayeh Piri-Gavgani; Mostafa Ghanei; Abolfazl Fateh; Seyed Davar Siadat; Leila Nematollahi; Fatemeh Rahimi-Jamnani. "Identification of two neutralizing human single-chain variable fragment antibodies targeting Staphylococcus aureus alpha-hemolysin". , 25, 10, 1401, 1207-1214. doi: 10.22038/ijbms.2022.64103.14253
Piri-Gavgani, Somayeh, Ghanei, Mostafa, Fateh, Abolfazl, Siadat, Seyed Davar, Nematollahi, Leila, Rahimi-Jamnani, Fatemeh. (1401). 'Identification of two neutralizing human single-chain variable fragment antibodies targeting Staphylococcus aureus alpha-hemolysin', , 25(10), pp. 1207-1214. doi: 10.22038/ijbms.2022.64103.14253
Piri-Gavgani, Somayeh, Ghanei, Mostafa, Fateh, Abolfazl, Siadat, Seyed Davar, Nematollahi, Leila, Rahimi-Jamnani, Fatemeh. Identification of two neutralizing human single-chain variable fragment antibodies targeting Staphylococcus aureus alpha-hemolysin. , 1401; 25(10): 1207-1214. doi: 10.22038/ijbms.2022.64103.14253

Identification of two neutralizing human single-chain variable fragment antibodies targeting Staphylococcus aureus alpha-hemolysin

Iranian Journal of Basic Medical Sciences
مقاله 7، دوره 25، شماره 10، دی 2022، صفحه 1207-1214    اصل مقاله (793.87 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2022.64103.14253
نویسندگان
Somayeh Piri-Gavgani1، 2؛ Mostafa Ghanei3؛ Abolfazl Fateh1، 2؛ Seyed Davar Siadat1، 2؛ Leila Nematollahi* 4؛ Fatemeh Rahimi-Jamnani* 1، 2
1Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
2Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran
3Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
4Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
چکیده
Objective(s): The inability of the host immune system to defeat Staphylococcus aureus is due to various secreted virulent factors such as leukocidins, superantigens, and hemolysins, which interrupt the function of immune components. Alpha-hemolysin is one of the most studied cytolysins due to its pronounced effect on developing staphylococcal infections. Alpha-hemolysin-neutralizing antibodies are among the best candidates for blocking the toxin activity and preventing S. aureus pathogenesis. 
Materials and Methods: A human single-chain variable fragment (scFv) phage display library was biopanned against alpha-hemolysin. The selected phage clones were assessed based on their binding ability to alpha-hemolysin. The binding specificity and affinity of two scFvs (designated SP192 and SP220) to alpha-hemolysin were determined by enzyme-linked immunosorbent assay. Furthermore, the neutralizing activity of SP192 and SP220 was examined by concurrent incubation of rabbit red blood cells (RBCs) with alpha-hemolysin and scFvs.
Results: SP192 and SP220 showed significant binding to alpha-hemolysin compared with the control proteins, including bovine serum albumin, human adiponectin, and toxic shock syndrome toxin-1. Besides, both scFvs showed high-affinity binding to alpha-hemolysin in the nanomolar range (Kaff: 0.9 and 0.7 nM-1, respectively), leading to marked inhibition of alpha-hemolysin-mediated lysis of rabbit RBCs (73% and 84% inhibition; respectively). 
Conclusion: SP192 and SP220 scFvs can potentially be used as alpha-hemolysin-neutralizing agents in conjunction with conventional antibiotics to combat S. aureus infections. 
کلیدواژه‌ها
Hemolysins؛ Monoclonal antibody؛ Single-chain variable - fragment؛ Staphylococcal infections؛ Staphylococcus aureus
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