Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design

Bonsignori, Mattia; Montefiori, David C.; Wu, Xueling; Chen, Xi; Hwang, Kwan‐Ki; Tsao, Chun-Yen; Kozink, Daniel M.; Parks, Robert; Tomaras, Georgia D.; Crump, John A.; Kapiga, Saidi; Sam, Noel E.; Kwong, Peter D.; Kepler, Thomas B.; Liao, Hua‐Xin; Mascola, John R.; Haynes, Barton F.

doi:10.1128/jvi.07163-11

Cited by 161 publications

(167 citation statements)

References 25 publications

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“…We observed antibodies from libraries enriched in long anionic loops, similar to those observed in antibodies PG9, CH01, and CAP256‐VRC26,6, 11, 28, 37, 102 to have poor solubility. Moreover, we are beginning to understand the features that allow for recognition of highly glycosylated antigens.…”

Section: Antibodyomics10supporting

confidence: 67%

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

Kwong

Chuang

DeKosky

et al. 2017

Immunological Reviews

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SummaryNumerous antibodies have been identified from HIV‐1‐infected donors that neutralize diverse strains of HIV‐1. These antibodies may provide the basis for a B cell‐mediated HIV‐1 vaccine. However, it has been unclear how to elicit similar antibodies by vaccination. To address this issue, we have undertaken an informatics‐based approach to understand the genetic and immunologic processes controlling the development of HIV‐1‐neutralizing antibodies. As DNA sequencing comprises the fastest growing database of biological information, we focused on incorporating next‐generation sequencing of B‐cell transcripts to determine the origin, maturation pathway, and prevalence of broadly neutralizing antibody lineages (Antibodyomics1, 2, 4, and 6). We also incorporated large‐scale robotic analyses of serum neutralization to identify and quantify neutralizing antibodies in donor cohorts (Antibodyomics3). Statistical analyses furnish another layer of insight (Antibodyomics5), with physical characteristics of antibodies and their targets through molecular dynamics simulations (Antibodyomics7) and free energy perturbation analyses (Antibodyomics8) providing information‐rich output. Functional interrogation of individual antibodies (Antibodyomics9) and synthetic antibody libraries (Antibodyomics10) also yields multi‐dimensional data by which to understand and improve antibodies. Antibodyomics, described here, thus comprise resolution‐enhancing tools, which collectively embody an information‐driven discovery engine aimed toward the development of effective B cell‐based vaccines.

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Section: Antibodyomics10supporting

confidence: 67%

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

Kwong

Chuang

DeKosky

et al. 2017

Immunological Reviews

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“…Moreover, recent success in establishing and monitoring large cohorts of HIV-infected individuals including those studied from transmission though bnAb development (5, 13, 14), and advances in antibody isolation and B cell repertoire analysis have enabled the identification of dozens of new bnAbs from multiple HIV-1 infected adults (14–27) and children (28, 29). In addition, more than one bnAb lineage can occur in the same individual (16, 30). In HIV-1 infected adults, plasma levels of bnAbs usually develop after 2–4 years of infection.…”

Section: Introductionmentioning

confidence: 99%

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

Bonsignori

Liao

Gao

et al. 2017

Immunological Reviews

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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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“…Recently, several potent CD4bs-directed broadly neutralizing human antibodies, such as VRC01, have been isolated from HIV-1-infected people (10,11). A common feature of these has been that they originate from a specific germ line V H allelic variant (60,61). This might indicate that immunogens need to bind to this germ line product in order to eventually result in affinity-matured VRC01-like antibodies.…”

Section: Discussionmentioning

confidence: 99%

Design of an Escherichia coli Expressed HIV-1 gp120 Fragment Immunogen That Binds to b12 and Induces Broad and Potent Neutralizing Antibodies

Bhattacharyya

Singh

Rathore

et al. 2013

Journal of Biological Chemistry

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Background: b12 is a broadly neutralizing human antibody that targets the conserved receptor binding site on HIV-1 gp120. Results: Designed gp120 fragment immunogens (b121a/b122a) targeting the b12 binding site were tested in rabbit immunization studies. Conclusion: Priming with b122a and boosting with gp120 elicited broadly neutralizing sera. Significance: gp120 fragment immunogens can elicit broadly neutralizing sera in small animals.

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Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design

Cited by 161 publications

References 25 publications

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

Antibodyomics: bioinformatics technologies for understanding B‐cell immunity to HIV‐1

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

Design of an Escherichia coli Expressed HIV-1 gp120 Fragment Immunogen That Binds to b12 and Induces Broad and Potent Neutralizing Antibodies

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