Enhanced immunogenicity of a human immunodeficiency virus type 1 env DNA vaccine by manipulating N-glycosylation signals
Identifieur interne : 003569 ( Main/Exploration ); précédent : 003568; suivant : 003570Enhanced immunogenicity of a human immunodeficiency virus type 1 env DNA vaccine by manipulating N-glycosylation signals
Auteurs : Anders Bolmstedt [Suède] ; Jorma Hinkula [Suède] ; Eric Rowcliffe [Suède] ; Marlene Biller [Suède] ; Britta Wahren [Suède] ; Sigvard Olofsson [Suède]Source :
- Vaccine [ 0264-410X ] ; 2002.
English descriptors
- KwdEn :
- Teeft :
- Amino acids, Antigen concentration, Arch virol, Assay, Bolmstedt, Cells transfected, Clone, Control cultures, Corresponding plasmid, Elisa, Elsevier science, Envelope gene, Envelope glycoprotein, Envelope oligomer, Epitope, Epitope exposure, Expression plasmid, Fusion activity, Gene products, Genetic immunization, Glycan, Glycans, Glycoprotein, Glycosylation, Glycosylation signal, Glycosylation site, Glycosylation sites, High titers, Higher neutralization titers, Hinkula, Host cell, Human virus, Human virus type, Immune response, Immunization, Immunogen, Immunogenicity, Insect cells, Mammalian cells, Monoclonal antibodies, Mutant, Natural infection, Neutralization, Neutralization assay, Neutralization epitopes, Neutralization titer, Neutralization titers, Neutralizing antibodies, Nucleic acid vaccination, Oligosaccharide, Olofsson, Peptide, Plasmid, Proliferation response, Proliferative response, Protein sciences, Regulatory genes, Relevant clones, Retrovirus, Retroviruses hinkula, Second protocol, Sodium pyruvate, Subtypes, Synthetic peptides, Titer, Transfected cells, Vaccine, Viral, Viral glycoproteins, Virol, Virus type, Wahren, Wild type, Wild type plasmid, Wild type virus.
Abstract
Abstract: DNA encoding HIV-1 env is a poorly efficient B-cell immunogen and one probable explanation is that the numerous gp120 N-linked glycans gp120 may interfere with B-cell epitope presentation. The N306 glycan in gp120 shields HIV-1 from neutralizing antibodies. A DNA immunogen lacking the N306 glycosylation signal (T308A) was constructed to determine whether this glycan affected the immune response. Mice were immunized intranasally twice with DNA containing either the wild type or the mutant env. Two additional groups were primed with wild type or mutant env and boosted with rgp160 protein, containing the complete set of N-linked glycans. Immunization with DNA alone resulted in priming of B-cell clones but was not sufficient to induce a complete antibody response. Animals primed with the N306 mutant and subsequently boosted with rgp160 protein displayed higher serum IgG-binding titers to gp120 than animals primed with wild type env DNA. The manipulation of the glycosylation sites of the env DNA strongly primes antibody responses (but non-neutralizing) as well as T-cell responses to the wild type strain gp160. However, priming with mutant plasmid did not result in higher neutralization titers to wild type or T308A-mutated virus than did the wild type plasmid. With the N306 mutant DNA we thus immunized a non-neutralization epitope, but obtained strong env-binding IgG after rgp160 boosting.
Url:
DOI: 10.1016/S0264-410X(01)00358-9
Affiliations:
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type="abbrev">JVAC</title><idno type="ISSN">0264-410X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2002">2002</date><biblScope unit="volume">20</biblScope><biblScope unit="issue">3–4</biblScope><biblScope unit="page" from="397">397</biblScope><biblScope unit="page" to="405">405</biblScope></imprint><idno type="ISSN">0264-410X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Genetic immunization</term><term>N-linked glycan</term><term>Neutralizing antibodies</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Amino acids</term><term>Antigen concentration</term><term>Arch virol</term><term>Assay</term><term>Bolmstedt</term><term>Cells transfected</term><term>Clone</term><term>Control cultures</term><term>Corresponding plasmid</term><term>Elisa</term><term>Elsevier science</term><term>Envelope gene</term><term>Envelope glycoprotein</term><term>Envelope oligomer</term><term>Epitope</term><term>Epitope exposure</term><term>Expression plasmid</term><term>Fusion activity</term><term>Gene products</term><term>Genetic immunization</term><term>Glycan</term><term>Glycans</term><term>Glycoprotein</term><term>Glycosylation</term><term>Glycosylation signal</term><term>Glycosylation site</term><term>Glycosylation sites</term><term>High titers</term><term>Higher neutralization titers</term><term>Hinkula</term><term>Host cell</term><term>Human virus</term><term>Human virus type</term><term>Immune response</term><term>Immunization</term><term>Immunogen</term><term>Immunogenicity</term><term>Insect cells</term><term>Mammalian cells</term><term>Monoclonal antibodies</term><term>Mutant</term><term>Natural infection</term><term>Neutralization</term><term>Neutralization assay</term><term>Neutralization epitopes</term><term>Neutralization titer</term><term>Neutralization titers</term><term>Neutralizing antibodies</term><term>Nucleic acid vaccination</term><term>Oligosaccharide</term><term>Olofsson</term><term>Peptide</term><term>Plasmid</term><term>Proliferation response</term><term>Proliferative response</term><term>Protein sciences</term><term>Regulatory genes</term><term>Relevant clones</term><term>Retrovirus</term><term>Retroviruses hinkula</term><term>Second protocol</term><term>Sodium pyruvate</term><term>Subtypes</term><term>Synthetic peptides</term><term>Titer</term><term>Transfected cells</term><term>Vaccine</term><term>Viral</term><term>Viral glycoproteins</term><term>Virol</term><term>Virus type</term><term>Wahren</term><term>Wild type</term><term>Wild type plasmid</term><term>Wild type virus</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: DNA encoding HIV-1 env is a poorly efficient B-cell immunogen and one probable explanation is that the numerous gp120 N-linked glycans gp120 may interfere with B-cell epitope presentation. The N306 glycan in gp120 shields HIV-1 from neutralizing antibodies. A DNA immunogen lacking the N306 glycosylation signal (T308A) was constructed to determine whether this glycan affected the immune response. Mice were immunized intranasally twice with DNA containing either the wild type or the mutant env. Two additional groups were primed with wild type or mutant env and boosted with rgp160 protein, containing the complete set of N-linked glycans. Immunization with DNA alone resulted in priming of B-cell clones but was not sufficient to induce a complete antibody response. Animals primed with the N306 mutant and subsequently boosted with rgp160 protein displayed higher serum IgG-binding titers to gp120 than animals primed with wild type env DNA. The manipulation of the glycosylation sites of the env DNA strongly primes antibody responses (but non-neutralizing) as well as T-cell responses to the wild type strain gp160. However, priming with mutant plasmid did not result in higher neutralization titers to wild type or T308A-mutated virus than did the wild type plasmid. With the N306 mutant DNA we thus immunized a non-neutralization epitope, but obtained strong env-binding IgG after rgp160 boosting.</div></front></TEI><affiliations><list><country><li>Suède</li></country></list><tree><country name="Suède"><noRegion><name sortKey="Bolmstedt, Anders" sort="Bolmstedt, Anders" uniqKey="Bolmstedt A" first="Anders" last="Bolmstedt">Anders Bolmstedt</name></noRegion><name sortKey="Biller, Marlene" sort="Biller, Marlene" uniqKey="Biller M" first="Marlene" last="Biller">Marlene Biller</name><name sortKey="Hinkula, Jorma" sort="Hinkula, Jorma" uniqKey="Hinkula J" first="Jorma" last="Hinkula">Jorma Hinkula</name><name sortKey="Olofsson, Sigvard" sort="Olofsson, Sigvard" uniqKey="Olofsson S" first="Sigvard" last="Olofsson">Sigvard Olofsson</name><name sortKey="Olofsson, Sigvard" sort="Olofsson, Sigvard" uniqKey="Olofsson S" first="Sigvard" last="Olofsson">Sigvard Olofsson</name><name sortKey="Rowcliffe, Eric" sort="Rowcliffe, Eric" uniqKey="Rowcliffe E" first="Eric" last="Rowcliffe">Eric Rowcliffe</name><name sortKey="Wahren, Britta" sort="Wahren, Britta" uniqKey="Wahren B" first="Britta" last="Wahren">Britta Wahren</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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