Characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: Implications for mechanisms of immune evasion and design of vaccine immunogens.
Identifieur interne : 001D50 ( Main/Exploration ); précédent : 001D49; suivant : 001D51Characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: Implications for mechanisms of immune evasion and design of vaccine immunogens.
Auteurs : Weizao Chen [États-Unis] ; Emily D. Streaker ; Daniel E. Russ ; Yang Feng ; Ponraj Prabakaran ; Dimiter S. DimitrovSource :
- Biochemical and biophysical research communications [ 1090-2104 ] ; 2012.
Descripteurs français
- KwdFr :
- Anticorps monoclonaux (immunologie), Anticorps monoclonaux (isolement et purification), Anticorps neutralisants (génétique), Anticorps neutralisants (immunologie), Banque de peptides, Données de séquences moléculaires, Glycoprotéines (immunologie), Humains, Immunité acquise, Protéines de l'enveloppe virale (immunologie), Sang foetal (immunologie), Structure tertiaire des protéines, Séquence d'acides aminés, VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie), Virus Hendra (immunologie), Virus du SRAS (immunologie).
- MESH :
- génétique : Anticorps neutralisants.
- immunologie : Anticorps monoclonaux, Anticorps neutralisants, Glycoprotéines, Protéines de l'enveloppe virale, Sang foetal, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Virus Hendra, Virus du SRAS.
- isolement et purification : Anticorps monoclonaux.
- Banque de peptides, Données de séquences moléculaires, Humains, Immunité acquise, Structure tertiaire des protéines, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Adaptive Immunity, Amino Acid Sequence, Antibodies, Monoclonal (immunology), Antibodies, Monoclonal (isolation & purification), Antibodies, Neutralizing (genetics), Antibodies, Neutralizing (immunology), Fetal Blood (immunology), Glycoproteins (immunology), HIV-1 (immunology), Hendra Virus (immunology), Humans, Molecular Sequence Data, Peptide Library, Protein Structure, Tertiary, SARS Virus (immunology), Viral Envelope Proteins (immunology).
- MESH :
- chemical , genetics : Antibodies, Neutralizing.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Glycoproteins, Viral Envelope Proteins.
- chemical , isolation & purification : Antibodies, Monoclonal.
- immunology : Fetal Blood, HIV-1, Hendra Virus, SARS Virus.
- Adaptive Immunity, Amino Acid Sequence, Humans, Molecular Sequence Data, Peptide Library, Protein Structure, Tertiary.
Abstract
We have previously observed that all known HIV-1 broadly neutralizing antibodies (bnAbs) are highly divergent from germline antibodies in contrast to bnAbs against Hendra virus, Nipah virus and SARS coronavirus (SARS CoV). We have hypothesized that because the germline antibodies are so different from the mature HIV-1-specific bnAbs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predecessor antibodies. To further validate the hypothesis and understand initial immune responses to different viruses, two phage-displayed human cord blood-derived IgM libraries were constructed which contained mostly germline antibodies or antibodies with very low level of somatic hypermutations. They were panned against different HIV-1 envelope glycoproteins (Envs), SARS CoV protein receptor-binding domain (RBD), and soluble Hendra virus G protein (sG). Despite a high sequence and combinatorial diversity observed in the cord blood-derived IgM antibody repertoire, no enrichment for binders of Envs was observed in contrast to considerable specific enrichments produced with panning against RBD and sG; one of the selected monoclonal antibodies (against the RBD) was of high (nM) affinity with only few somatic mutations. These results further support and expand our initial hypothesis for fundamental differences in immune responses leading to elicitation of bnAbs against HIV-1 compared to SARS CoV and Hendra virus. HIV-1 uses a strategy to minimize or eliminate strong binding of germline antibodies to its Env; in contrast, SARS CoV and Hendra virus, and perhaps other viruses causing acute infections, can bind germline antibody or minimally somatically mutated antibodies with relatively high affinity which could be one of the reasons for the success of sG and RBD as vaccine immunogens.
DOI: 10.1016/j.bbrc.2011.12.089
PubMed: 22226962
Affiliations:
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Le document en format XML
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Streaker</name></author><author><name sortKey="Russ, Daniel E" sort="Russ, Daniel E" uniqKey="Russ D" first="Daniel E" last="Russ">Daniel E. Russ</name></author><author><name sortKey="Feng, Yang" sort="Feng, Yang" uniqKey="Feng Y" first="Yang" last="Feng">Yang Feng</name></author><author><name sortKey="Prabakaran, Ponraj" sort="Prabakaran, Ponraj" uniqKey="Prabakaran P" first="Ponraj" last="Prabakaran">Ponraj Prabakaran</name></author><author><name sortKey="Dimitrov, Dimiter S" sort="Dimitrov, Dimiter S" uniqKey="Dimitrov D" first="Dimiter S" last="Dimitrov">Dimiter S. Dimitrov</name></author></analytic><series><title level="j">Biochemical and biophysical research communications</title><idno type="eISSN">1090-2104</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptive Immunity</term><term>Amino Acid Sequence</term><term>Antibodies, Monoclonal (immunology)</term><term>Antibodies, Monoclonal (isolation & purification)</term><term>Antibodies, Neutralizing (genetics)</term><term>Antibodies, Neutralizing (immunology)</term><term>Fetal Blood (immunology)</term><term>Glycoproteins (immunology)</term><term>HIV-1 (immunology)</term><term>Hendra Virus (immunology)</term><term>Humans</term><term>Molecular Sequence Data</term><term>Peptide Library</term><term>Protein Structure, Tertiary</term><term>SARS Virus (immunology)</term><term>Viral Envelope Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps monoclonaux (immunologie)</term><term>Anticorps monoclonaux (isolement et purification)</term><term>Anticorps neutralisants (génétique)</term><term>Anticorps neutralisants (immunologie)</term><term>Banque de peptides</term><term>Données de séquences moléculaires</term><term>Glycoprotéines (immunologie)</term><term>Humains</term><term>Immunité acquise</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Sang foetal (immunologie)</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie)</term><term>Virus Hendra (immunologie)</term><term>Virus du SRAS (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antibodies, Neutralizing</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Neutralizing</term><term>Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Antibodies, Monoclonal</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Anticorps neutralisants</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps monoclonaux</term><term>Anticorps neutralisants</term><term>Glycoprotéines</term><term>Protéines de l'enveloppe virale</term><term>Sang foetal</term><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term><term>Virus Hendra</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Fetal Blood</term><term>HIV-1</term><term>Hendra Virus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Anticorps monoclonaux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adaptive Immunity</term><term>Amino Acid Sequence</term><term>Humans</term><term>Molecular Sequence Data</term><term>Peptide Library</term><term>Protein Structure, Tertiary</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Banque de peptides</term><term>Données de séquences moléculaires</term><term>Humains</term><term>Immunité acquise</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have previously observed that all known HIV-1 broadly neutralizing antibodies (bnAbs) are highly divergent from germline antibodies in contrast to bnAbs against Hendra virus, Nipah virus and SARS coronavirus (SARS CoV). We have hypothesized that because the germline antibodies are so different from the mature HIV-1-specific bnAbs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predecessor antibodies. To further validate the hypothesis and understand initial immune responses to different viruses, two phage-displayed human cord blood-derived IgM libraries were constructed which contained mostly germline antibodies or antibodies with very low level of somatic hypermutations. They were panned against different HIV-1 envelope glycoproteins (Envs), SARS CoV protein receptor-binding domain (RBD), and soluble Hendra virus G protein (sG). Despite a high sequence and combinatorial diversity observed in the cord blood-derived IgM antibody repertoire, no enrichment for binders of Envs was observed in contrast to considerable specific enrichments produced with panning against RBD and sG; one of the selected monoclonal antibodies (against the RBD) was of high (nM) affinity with only few somatic mutations. These results further support and expand our initial hypothesis for fundamental differences in immune responses leading to elicitation of bnAbs against HIV-1 compared to SARS CoV and Hendra virus. HIV-1 uses a strategy to minimize or eliminate strong binding of germline antibodies to its Env; in contrast, SARS CoV and Hendra virus, and perhaps other viruses causing acute infections, can bind germline antibody or minimally somatically mutated antibodies with relatively high affinity which could be one of the reasons for the success of sG and RBD as vaccine immunogens.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Dimitrov, Dimiter S" sort="Dimitrov, Dimiter S" uniqKey="Dimitrov D" first="Dimiter S" last="Dimitrov">Dimiter S. Dimitrov</name><name sortKey="Feng, Yang" sort="Feng, Yang" uniqKey="Feng Y" first="Yang" last="Feng">Yang Feng</name><name sortKey="Prabakaran, Ponraj" sort="Prabakaran, Ponraj" uniqKey="Prabakaran P" first="Ponraj" last="Prabakaran">Ponraj Prabakaran</name><name sortKey="Russ, Daniel E" sort="Russ, Daniel E" uniqKey="Russ D" first="Daniel E" last="Russ">Daniel E. Russ</name><name sortKey="Streaker, Emily D" sort="Streaker, Emily D" uniqKey="Streaker E" first="Emily D" last="Streaker">Emily D. Streaker</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Chen, Weizao" sort="Chen, Weizao" uniqKey="Chen W" first="Weizao" last="Chen">Weizao Chen</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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