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Immunological Reviews
Article . 2017 . Peer-reviewed
License: Wiley Online Library User Agreement
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Germline‐targeting immunogens

Authors: Leonidas, Stamatatos; Marie, Pancera; Andrew T, McGuire;

Germline‐targeting immunogens

Abstract

SummaryIn 2009, Dimitrov's group reported that the inferred germline (iGL) forms of several HIV‐1 broadly neutralizing antibodies (bNAbs) did not display measurable binding to a recombinant gp140 Env protein (derived from the dual‐tropic 89.6 virus), which was efficiently recognized by the mature (somatically mutated) antibodies. At that time, a small number of bNAbs were available, but in the following years, the implementation of high‐throughput B‐cell isolation and sequencing assays and of screening methodologies facilitated the isolation of greater numbers of bNAbs from infected subjects. Using these newest bNAbs, and a wide range of diverse recombinant Envs, we and others confirmed the observations made by Dimitrov's group. The results from these studies created a paradigm shift in our collective thinking as to why recombinant Envs are ineffective in eliciting bNAbs and has led to the “germline‐targeting” immunization approach. Here we discuss this approach in detail: what has been done so far, the advantages and limitations of the current germline‐targeting immunogens and of the animal models used to test them, and we conclude with a few thoughts about future directions in this area of research.

Keywords

B-Lymphocytes, Vaccination, env Gene Products, Human Immunodeficiency Virus, HIV Infections, HIV Antibodies, Antibodies, Neutralizing, High-Throughput Screening Assays, Viral Envelope Proteins, HIV-1, Animals, Humans, Protein Binding

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
126
Top 1%
Top 10%
Top 1%
bronze