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Article: Identification of Non-HIV Immunogens That Bind to Germline b12 Predecessors and Prime for Elicitation of Cross-clade Neutralizing HIV-1 Antibodies

TitleIdentification of Non-HIV Immunogens That Bind to Germline b12 Predecessors and Prime for Elicitation of Cross-clade Neutralizing HIV-1 Antibodies
Authors
Issue Date2015
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2015, v. 10 n. 5, p. e0126428 How to Cite?
AbstractA fundamental challenge for developing an effective and safe HIV-1 vaccine is to identify vaccine immunogens that can initiate and maintain immune responses leading to elicitation of broadly neutralizing HIV-1 antibodies (bnAbs) through complex maturation pathways. We have previously found that HIV-1 envelope glycoproteins (Env) lack measurable binding to putative germline predecessors of known bnAbs and proposed to search for non-HIV immunogens that could initiate their somatic maturation. Using bnAb b12 as a model bnAb and yeast display technology, we isolated five (poly) peptides from plant leaves, insects, E. coli strains, and sea water microbes that bind to b12 putative germline and intermediate antibodies. Rabbit immunization with the (poly) peptides alone induced high titers of cross-reactive antibodies that neutralized HIV-1 isolates SF162 and JRFL. Priming rabbits with the (poly) peptides followed by boosts with trimeric gp140(SF162) and then resurfaced Env (RSC3) induced antibodies that competed with mature b12 and neutralized tier 1 and 2 viruses from clade B, C and E, while control rabbits without (poly) peptide priming induced antibodies that did not compete with mature b12 and neutralized fewer isolates. The degree of competition with mature b12 for binding to gp140SF162 correlated with the neutralizing activity of the rabbit IgG. Reversing the order of the two boosting immunogens significantly affected the binding profile and neutralization potency of the rabbit IgG. Our study is the first to provide evidence that appears to support the concept that non-HIV immunogens may initiate immune responses leading to elicitation of cross-clade neutralizing antibodies.
Persistent Identifierhttp://hdl.handle.net/10722/227870
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
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DC FieldValueLanguage
dc.contributor.authorYang, Z-
dc.contributor.authorLi, J-
dc.contributor.authorLiu, Q-
dc.contributor.authorYuan, T-
dc.contributor.authorZhang, Y-
dc.contributor.authorChen, LQ-
dc.contributor.authorLou, Q-
dc.contributor.authorSun, Z-
dc.contributor.authorYing, H-
dc.contributor.authorXu, J-
dc.contributor.authorDimitrov, DS-
dc.contributor.authorZhang, MY-
dc.date.accessioned2016-07-21T05:20:34Z-
dc.date.available2016-07-21T05:20:34Z-
dc.date.issued2015-
dc.identifier.citationPlos One, 2015, v. 10 n. 5, p. e0126428-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/227870-
dc.description.abstractA fundamental challenge for developing an effective and safe HIV-1 vaccine is to identify vaccine immunogens that can initiate and maintain immune responses leading to elicitation of broadly neutralizing HIV-1 antibodies (bnAbs) through complex maturation pathways. We have previously found that HIV-1 envelope glycoproteins (Env) lack measurable binding to putative germline predecessors of known bnAbs and proposed to search for non-HIV immunogens that could initiate their somatic maturation. Using bnAb b12 as a model bnAb and yeast display technology, we isolated five (poly) peptides from plant leaves, insects, E. coli strains, and sea water microbes that bind to b12 putative germline and intermediate antibodies. Rabbit immunization with the (poly) peptides alone induced high titers of cross-reactive antibodies that neutralized HIV-1 isolates SF162 and JRFL. Priming rabbits with the (poly) peptides followed by boosts with trimeric gp140(SF162) and then resurfaced Env (RSC3) induced antibodies that competed with mature b12 and neutralized tier 1 and 2 viruses from clade B, C and E, while control rabbits without (poly) peptide priming induced antibodies that did not compete with mature b12 and neutralized fewer isolates. The degree of competition with mature b12 for binding to gp140SF162 correlated with the neutralizing activity of the rabbit IgG. Reversing the order of the two boosting immunogens significantly affected the binding profile and neutralization potency of the rabbit IgG. Our study is the first to provide evidence that appears to support the concept that non-HIV immunogens may initiate immune responses leading to elicitation of cross-clade neutralizing antibodies.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPlos One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleIdentification of Non-HIV Immunogens That Bind to Germline b12 Predecessors and Prime for Elicitation of Cross-clade Neutralizing HIV-1 Antibodies-
dc.typeArticle-
dc.identifier.emailZhang, MY: zhangmy@hku.hk-
dc.identifier.authorityZhang, MY=rp01409-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0126428-
dc.identifier.pmid26010511-
dc.identifier.volume10-
dc.identifier.issue5-
dc.identifier.spagee0126428-
dc.identifier.epagee0126428-
dc.identifier.isiWOS:000355183900028-
dc.publisher.placeUnited States-
dc.relation.projectGuiding the immune response: a novel approach for HIV-1 vaccine development-

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