Quantitative analysis of anti-hepatitis C virus anti body-secreting B cells in patients with chronic hepatitis C

Copyright © 2006 American Association for the Study of Liver DiseasesArticleHEPATOLOGY. 43(1): 91-99 (2006)journal articl

Quantitative analysis of anti-hepatitis C virus anti body-secreting B cells in patients with chronic hepatitis C

Copyright © 2006 American Association for the Study of Liver DiseasesArticleapplication/pdfHEPATOLOGY. 43(1): 91-99 (2006)journal articl

Humanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1

Hemagglutinin (HA), the major antigen on the surface of influenza viruses, is the primary target for neutralizing antibodies and vaccine design. However, frequent mutations in this gene allow the virus to evade host immune responses and conventional prophylaxis and treatment. In this report, we humanized 4D1 and 10F7 mouse monoclonal antibodies (mAbs) that, we had previously shown to display broad-spectrum neutralization to avian H5N1 virus. The genes of variable (V) regions of 4D1 and 10F7 mAbs were combined with constant region of human antibody to construct the chimeric antibodies (cAbs). The results of hemagglutinin inhibition (HI) and neutralization assays showed that 4D1 and 10F7 cAbs were functional and retained broad-spectrum reactivity. Antibody competitive ELISA and affinity tests indicated that the cAbs recognized the same epitope as the parent mAbs with similar affinity. In animal experiments, the 10F7 cAb showed full protection against lethal challenge of highly virulent avian H5N1 virus, A/BH Goose/QH/15C/2005, in all infected mice. These humanized broad-spectrum antibodies may be potentially important for the control of both current and future antigenic variants of H5N1 virus. © 2010 Elsevier B.V.link_to_subscribed_fulltex

Antibody reactivity of conformational peptide mimics of a conserved H5N1 neutralization site in different fusion proteins

Science and Technology Foundation of Fujian Province [2008Y0059, F2006BAI01B06]; Chinese Ministry of Education [108157]; Ministry of Science and Technology [2005DC105006]; Chinese Ministry of Public Health [2008ZX10004-006]Several peptide mimics of a conserved H5N1 avian influenza virus neutralization site recognized by 8H5 mAb have been reported previously. In this study, the secondary and possibly higher structural orders of the peptide mimics 122 and 125 were investigated and found to be closely related to the specific binding with 8H5 mAb. These two peptide mimics were fused to three different carrier proteins, and the antibody binding activities were recovered in 4 of the 11 fusion proteins. HEV structural protein p239 and HBc were more suitable than the outer membrane protein T47 of the Treponema pallidum particle for the recovery of reactivity. The increase in the copy number of peptide mimics was important for the recovery of antibody-binding activity and the interaction between peptide and carrier protein may affect the spatial structure of both the peptide and the carrier protein. These results are likely to be of relevance for conformational peptide mimics in diagnostic tests, vaccine and inhibitors

Broad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopes

Background. Passive immunization with human H5 antisera or H5-specific monoclonal antibodies (MAbs) has potential as an effective treatment for acute H5N1 influenza virus infection, but its efficacy against antigenically diverse H5N1 viruses is unconfirmed. Methods. Cross-protection against antigenically diverse H5N1 strains with H5-specific MAbs, generated by successive immunization of antigenically distinct strains, was evaluated in mice. Results. A panel of 52 broadly cross-reactive H5 specific MAbs were generated and characterized. One of these MAbs, 13D4, has been demonstrated to protect mice against lethal challenge by 4 H5N1 strains representing the current major genetic populations, clades 1, 2.1, 2.2, and 2.3, even at a stage of infection when H5N1 virus has disseminated beyond the pulmonary system. Complete neutralization of virus in lung tissue of infected animals was observed 24 h after treatment with 13D4. Mapping of this MAb with escape mutants showed it to bind to 2 conserved, possibly critical, sites of H5N1 hemagglutinin, 152 and 182. Conclusion. Generation of broadly cross-protective MAbs against H5N1 influenza virus may be optimized by selecting MAbs that target conserved sites in hemagglutinin. H5 MAbs such as 13D4 may prove to have therapeutic value in controlling infection due to current and future H5N1 variants. © 2008 by the Infectious Diseases Society of America. All rights reserved.link_to_OA_fulltex

Antibody reactivity of conformational peptide mimics of a conserved H5N1 neutralization site in different fusion proteins

Several peptide mimics of a conserved H5N1 avian influenza virus neutralization site recognized by 8H5 mAb have been reported previously. In this study, the secondary and possibly higher structural orders of the peptide mimics 122 and 125 were investigated and found to be closely related to the specific binding with 8H5 mAb. These two peptide mimics were fused to three different carrier proteins, and the antibody binding activities were recovered in 4 of the 11 fusion proteins. HEV structural protein p239 and HBc were more suitable than the outer membrane protein T47 of the Treponema pallidum particle for the recovery of reactivity. The increase in the copy number of peptide mimics was important for the recovery of antibody-binding activity and the interaction between peptide and carrier protein may affect the spatial structure of both the peptide and the carrier protein. These results are likely to be of relevance for conformational peptide mimics in diagnostic tests, vaccine and inhibitors. © Springer-Verlag 2009.link_to_subscribed_fulltex

Investigation of SEN virus infection in patients with cryptogenic acute liver failure, hepatitis-associated aplastic anemia, or acute and chronic non-A-E hepatitis

SEN virus ( SENV) has been tentatively linked to transfusion- associated non - A - E hepatitis. We investigated SENV’s role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants ( SENV- D and SENV- H) in 1706 patients and control subjects. SENV was detected in 54 ( 22%) of 248 patients with acute or chronic non - A - E hepatitis, 9 ( 35%) of 26 patients with hepatitis-associated aplastic anemia, and 0 of 17 patients with cryptogenic acute liver failure, compared with 150 ( 24%) of 621 control subjects with liver disease and 76 ( 10%) of 794 healthy control subjects. When controlling for geographic region, the prevalence of SENV among case and control subjects was not significantly different. The severity of acute or chronic hepatitis A, B, or C was not influenced by coexisting SENV infection. No etiological role for SENV in the cause of cryptogenic hepatitis could be demonstrated