tetano
Editor, Senior Moderator
PLoS One. 2014 Feb 18;9(2):e88777. doi: 10.1371/journal.pone.0088777. eCollection 2014.
A High-Affinity CDR-Grafted Antibody against Influenza A H5N1 Viruses Recognizes a Conserved Epitope of H5 Hemagglutinin.
Xiong F1, Xia L2, Wang J3, Wu B2, Wang D2, Yuan L2, Cheng Y2, Zhu H2, Che X4, Zhang Q5, Zhao G2, Wang Y6.
Author information
Abstract
Highly pathogenic avian influenza (HPAI) H5N1 virus infection is still a potential threat to public health worldwide. While vaccines and antiviral drugs are currently under development, neutralizing antibodies could offer an alternative strategy to prevent and treat H5N1 virus infection. In the present study, we had developed a humanized antibody against H5N1 viruses from mouse-derived hybridoma in order to minimize its immunogenicity for potential clinical application. The humanized antibody hH5M9 was generated by transferring the mouse complementarity determining region (CDR) residues together with four key framework region (FR) residues onto the FR of the human antibody. This humanized antibody exhibited high affinity and specificity comparable to the parental mouse or chimeric counterpart with broad and strong neutralization activity against all H5N1 clades and subclades except for Egypt clades investigated. Furthermore, through epitope mapping we identified a linear epitope on the top region of hemagglutinin (HA) that was H5N1 specific and conserved. Our results for the first time reported a humanized antibody against H5N1 viruses by CDR grafting method. With the expected lower immunogenicity, this humanized antibody was expected to be more efficacious than murine or human-mouse chimeric antibodies for future application in humans.
PMID:
24558425
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24558425
A High-Affinity CDR-Grafted Antibody against Influenza A H5N1 Viruses Recognizes a Conserved Epitope of H5 Hemagglutinin.
Xiong F1, Xia L2, Wang J3, Wu B2, Wang D2, Yuan L2, Cheng Y2, Zhu H2, Che X4, Zhang Q5, Zhao G2, Wang Y6.
Author information
Abstract
Highly pathogenic avian influenza (HPAI) H5N1 virus infection is still a potential threat to public health worldwide. While vaccines and antiviral drugs are currently under development, neutralizing antibodies could offer an alternative strategy to prevent and treat H5N1 virus infection. In the present study, we had developed a humanized antibody against H5N1 viruses from mouse-derived hybridoma in order to minimize its immunogenicity for potential clinical application. The humanized antibody hH5M9 was generated by transferring the mouse complementarity determining region (CDR) residues together with four key framework region (FR) residues onto the FR of the human antibody. This humanized antibody exhibited high affinity and specificity comparable to the parental mouse or chimeric counterpart with broad and strong neutralization activity against all H5N1 clades and subclades except for Egypt clades investigated. Furthermore, through epitope mapping we identified a linear epitope on the top region of hemagglutinin (HA) that was H5N1 specific and conserved. Our results for the first time reported a humanized antibody against H5N1 viruses by CDR grafting method. With the expected lower immunogenicity, this humanized antibody was expected to be more efficacious than murine or human-mouse chimeric antibodies for future application in humans.
PMID:
24558425
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24558425