tetano
Editor, Senior Moderator
PLoS One. 2012;7(6):e39075. Epub 2012 Jun 13.
Broader Neutralizing Antibodies against H5N1 Viruses Using Prime-Boost Immunization of Hyperglycosylated Hemagglutinin DNA and Virus-Like Particles.
Lin SC, Lin YF, Chong P, Wu SC.
Source
Institute of Biotechnology, National Tsing Hua University, Hisnchu, Taiwan.
Abstract
BACKGROUND:
Highly pathogenic avian influenza (HPAI) H5N1 viruses and their transmission capability from birds to humans have raised global concerns about a potential human pandemic. The inherent nature of antigenic changes in influenza viruses has not been sufficiently taken into account in immunogen designs for broadly protective HPAI H5N1 vaccines.
METHODS:
We designed a hyperglycosylated HA vaccine using N-linked glycan masking on highly variable sequences in the HA1 globular head. Immunization of these hyperglycosylated HA DNA vaccines followed by a flagellin-containing virus-like particle booster in mice was conducted to evaluate neutralizing antibody responses against various clades of HPAI H5N1 viruses.
RESULTS:
We introduced nine N-X-S/T motifs in five HA1 regions: 83NNT, 86NNT, 94NFT, 127NSS, 138NRT, 156NTT, 161NRS, 182NDT, and 252NAT according to sequence alignment analyses from 163 HPAI H5N1 human isolates. Although no significant differences of anti-HA total IgG titers were found with these hyperglycosyalted HA compared to the wild-type control, the 83NNT and 127NSS mutants elicited significantly potent cross-clade neutralizing antibodies against HPAI H5N1 viruses.
CONCLUSIONS:
This finding may have value in terms of novel immunogen design for developing cross-protective H5N1 vaccines.
PMID:
22720032
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/22720032
Broader Neutralizing Antibodies against H5N1 Viruses Using Prime-Boost Immunization of Hyperglycosylated Hemagglutinin DNA and Virus-Like Particles.
Lin SC, Lin YF, Chong P, Wu SC.
Source
Institute of Biotechnology, National Tsing Hua University, Hisnchu, Taiwan.
Abstract
BACKGROUND:
Highly pathogenic avian influenza (HPAI) H5N1 viruses and their transmission capability from birds to humans have raised global concerns about a potential human pandemic. The inherent nature of antigenic changes in influenza viruses has not been sufficiently taken into account in immunogen designs for broadly protective HPAI H5N1 vaccines.
METHODS:
We designed a hyperglycosylated HA vaccine using N-linked glycan masking on highly variable sequences in the HA1 globular head. Immunization of these hyperglycosylated HA DNA vaccines followed by a flagellin-containing virus-like particle booster in mice was conducted to evaluate neutralizing antibody responses against various clades of HPAI H5N1 viruses.
RESULTS:
We introduced nine N-X-S/T motifs in five HA1 regions: 83NNT, 86NNT, 94NFT, 127NSS, 138NRT, 156NTT, 161NRS, 182NDT, and 252NAT according to sequence alignment analyses from 163 HPAI H5N1 human isolates. Although no significant differences of anti-HA total IgG titers were found with these hyperglycosyalted HA compared to the wild-type control, the 83NNT and 127NSS mutants elicited significantly potent cross-clade neutralizing antibodies against HPAI H5N1 viruses.
CONCLUSIONS:
This finding may have value in terms of novel immunogen design for developing cross-protective H5N1 vaccines.
PMID:
22720032
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/22720032