Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies

Binley, James Μ.; Wrin, Terri; Korber, Bette T.; Zwick, Michael B.; Wang, Meng; Chappey, Colombe; Stiegler, Gabriela; Kunert, Renate; Zolla‐Pazner, Susan; Katinger, Hermann; Petropoulos, Christos J.; Burton, Dennis R.

doi:10.1128/jvi.78.23.13232-13252.2004

Cited by 662 publications

(809 citation statements)

References 152 publications

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“…Very few bnAbs were known prior to this time (e.g., b12, 2G12, 2F5, 4E10), and the breadth and potency of these early bnAbs pale in comparison to the newer bnAbs (12). High throughput assay technologies with molecularly cloned Env-pseudotyped viruses (67–69), combined with a heightened awareness of the importance of the “Tier 2” neutralization phenotype of most circulating strains (70, 71) were major contributors. New reporter gene assays in either TZM-bl or U87.CD4.CCR5.CXCR4 became available that are more rapid, sensitive and less costly than other assays, and are amenable to high standards of optimization and validation (72).…”

Section: Neutralization Assessment Of Bnab Lineage Developmentmentioning

confidence: 99%

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Bonsignori

Liao

Gao

et al. 2017

Immunological Reviews

156

146

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Summary Induction of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of HIV-1 infection, and then only years after HIV transmission. Thus, the concept has emerged that one path to induction of bnAbs is to define the viral and immunologic events that occur during HIV-1 infection, and then to mimic those events with a vaccine formulation. This concept has led to efforts to map both virus and antibody events that occur from the time of HIV-1 transmission to development of bnAbs. This work has revealed that a virus-antibody “arms race” occurs in which a HIV-1 transmitted/founder (TF) Env induces autologous neutralizing antibodies that can not only neutralize the TF virus but also can select virus escape mutants that in turn select affinity-matured neutralizing antibodies. From these studies has come a picture of bnAb development that has led to new insights in host-pathogen interactions and, as well, led to insight into immunologic mechanisms of control of bnAb development. Here we review the progress to date in elucidating bnAb B cell lineages in HIV-1 infection, discuss new research leading to understanding the immunologic mechanisms of bnAb induction, and address issues relevant to the use of this information for the design of new HIV-1 sequential envelope vaccine candidates.

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Section: Neutralization Assessment Of Bnab Lineage Developmentmentioning

confidence: 99%

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Bonsignori

Liao

Gao

et al. 2017

Immunological Reviews

156

146

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“…High‐throughput neutralization assays were a major factor in changing that situation. The ability to analyze mAb and serum activity against large panels of viruses was demonstrated20 and subsequently used to evaluate large numbers of HIV‐infected donors in the International AIDS Vaccine Initiative (IAVI) Protocol G and C studies to identify those with exceptionally potent and broad sera,8 map the specificities underlying these responses,7, 21 and then isolate bnAbs from these individuals 22, 23, 24, 25, 26, 27, 28. Independently, the standardization of the TZM‐bl neutralization assay and the definition of neutralization sensitivity tiers29, 30, 31 allowed much more rigorous serum analysis.…”

Section: Introductionmentioning

confidence: 99%

Identification and specificity of broadly neutralizing antibodies against HIV

McCoy

Burton

2017

Immunological Reviews

Self Cite

204

191

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SummaryBeginning in 2009, studies of the humoral responses of HIV‐positive individuals have led to the identification of scores, if not hundreds, of antibodies that are both broadly reactive and potently neutralizing. This development has provided renewed impetus toward an HIV vaccine and led directly to the development of novel immunogens. Advances in identification of donors with the most potent and broad anti‐HIV serum neutralizing responses were crucial in this effort. Equally, development of methods for the rapid generation of human antibodies from these donors was pivotal. Primarily these methods comprise single B‐cell culture coupled to high‐throughput neutralization screening and flow cytometry‐based sorting of single B cells using HIV envelope protein baits. In this review, the advantages and disadvantages of these methodologies are discussed in the context of the specificities targeted by individual antibodies and the need for further improvements to evaluate HIV vaccine candidates.

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“…The MPER is a highly conserved region among various HIV-1 isolates and is critical for HIV-1 mediated membrane fusion and infection [21,22]. In an in vitro study of cross-clade neutralization using a pseudotyped virus assay, 4E10 appeared to be the broadest neutralizing antibody described to date with activity against isolates from different clades [23]. 2F5 and 4E10 neutralized 80 and 100%, respectively, of 91 viruses that were cloned directly from newly infected patients that had a negative or indeterminate serology [24].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, it was shown that 2F5 and 4E10 mAbs were more potent in inhibiting viruses from acutely infected individuals than viruses from chronically infected patients [25]. However, experiments revealed that Env -pseudotyped viruses were more sensitive to neutralization than were their classical peripheral blood mononuclear cell (PBMC)-grown viruses, against which these antibodies manifest less potent activity with reduced breadth [23,26]. The molecular bases of these observed differences between pseudovirus and PBMC-derived virus remains to be fully explained [27].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state

Kim

Qiao

et al. 2007

Vaccine

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The conserved membrane proximal external region (MPER) of the ectodomain of human immunodeficiency virus type 1 (HIV-1) gp41 is the target of two broadly neutralizing antibodies, 2F5 and 4E10. However, no neutralizing antibodies have been elicited against immunogens bearing these epitopes. Given that structural and biochemical studies suggest that the lipid membrane of the virion is involved in their proper configuration, HIV-1 gp41 derivatives in a pre-fusion state were expressed on the surface of immature virus like particles (VLP) derived from Sf9 cells. Guinea pigs were immunized with three doses of VLPs or Sf9 cells presenting gp41 derivatives with or without E. coli heat-labile enterotoxin (LT) as an adjuvant. While immune sera contained high titer anti-VLP antibodies, the specific anti-gp41 antibody responses were low with no neutralizing antibodies detected. An explanation for this absence may be the low level of gp41 expression relative to the many other proteins derived from host cells which are incorporated onto the VLP surface. In addition, the anti-gp41 immune response was preferentially directed to the C-helical domain, away from the MPER. Future vaccine design needs to contend with the complexity of epitope display as well as immunodominance.

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Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies

Cited by 662 publications

References 152 publications

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Antibody‐virus co‐evolution in HIV infection: paths for HIV vaccine development

Identification and specificity of broadly neutralizing antibodies against HIV

Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state

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