tetano
Editor, Senior Moderator
Antiviral Res. 2012 Dec 25. pii: S0166-3542(12)00294-X. doi: 10.1016/j.antiviral.2012.12.014. [Epub ahead of print]
Formatted single-domain antibodies can protect mice against infection with influenza virus (H5N2).
Tillib SV, Ivanova TI, Vasilev LA, Rutovskaya MV, Saakyan SA, Gribova IY, Tutykhina IL, Sedova ES, Lysenko AA, Shmarov MM, Logunov DY, Naroditsky BS, Gintsburg AL.
Source
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia. Electronic address: sergei.tillib@gmail.com.
Abstract
This work continues a series of recently published studies that employ recombinant single-domain antibody (sdAb, or nanobody?) generation technologies to battle viruses by a passive immunization approach. As a proof of principle, we describe a modified technique to efficiently generate protective molecules against a particular strain of influenza virus within a reasonably short period of time. This approach starts with the immunization of a camel (Camelus bactrianus) with the specified antigen-enriched material presented in as natural a form as possible. An avian influenza virus A/Mallard/Pennsylvania/10218/84 (H5N2) adapted for mice was used as a model source of antigens for both the immunization and phage display-based selection procedures. To significantly increase activities of initially selected monovalent single-domain antibodies, we propose a new type of sdAb formatting that involves the addition of a special type of coiled-coil sequence, the isoleucine zipper domain (ILZ). Presumably, the ILZ-containing peptides adopt trimeric parallel conformations. After the formatting, the biological activities (virus neutralization) of the initially selected anti-influenza virus (H5N2) sdAbs were significantly increased. Intraperitoneal or intranasal administration of the formatted sdAb at 2 hours before or 24 hours after viral challenge specifically protects mice from lethal infection with influenza virus. We hope that the described approach combined with the selection focused on particular conservative epitopes will lead to the generation of sdAb-based molecules protective against a broad spectrum of influenza virus subtypes.
Copyright ? 2012. Published by Elsevier B.V.
PMID:
23274623
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23274623
Formatted single-domain antibodies can protect mice against infection with influenza virus (H5N2).
Tillib SV, Ivanova TI, Vasilev LA, Rutovskaya MV, Saakyan SA, Gribova IY, Tutykhina IL, Sedova ES, Lysenko AA, Shmarov MM, Logunov DY, Naroditsky BS, Gintsburg AL.
Source
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia. Electronic address: sergei.tillib@gmail.com.
Abstract
This work continues a series of recently published studies that employ recombinant single-domain antibody (sdAb, or nanobody?) generation technologies to battle viruses by a passive immunization approach. As a proof of principle, we describe a modified technique to efficiently generate protective molecules against a particular strain of influenza virus within a reasonably short period of time. This approach starts with the immunization of a camel (Camelus bactrianus) with the specified antigen-enriched material presented in as natural a form as possible. An avian influenza virus A/Mallard/Pennsylvania/10218/84 (H5N2) adapted for mice was used as a model source of antigens for both the immunization and phage display-based selection procedures. To significantly increase activities of initially selected monovalent single-domain antibodies, we propose a new type of sdAb formatting that involves the addition of a special type of coiled-coil sequence, the isoleucine zipper domain (ILZ). Presumably, the ILZ-containing peptides adopt trimeric parallel conformations. After the formatting, the biological activities (virus neutralization) of the initially selected anti-influenza virus (H5N2) sdAbs were significantly increased. Intraperitoneal or intranasal administration of the formatted sdAb at 2 hours before or 24 hours after viral challenge specifically protects mice from lethal infection with influenza virus. We hope that the described approach combined with the selection focused on particular conservative epitopes will lead to the generation of sdAb-based molecules protective against a broad spectrum of influenza virus subtypes.
Copyright ? 2012. Published by Elsevier B.V.
PMID:
23274623
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23274623