期刊
IMMUNOLOGICAL REVIEWS
卷 275, 期 1, 页码 203-216出版社
WILEY
DOI: 10.1111/imr.12483
关键词
B-cell receptors; Env; germline antibodies; HIV; immunogens
类别
资金
- NIH [R21 AI127249, R01 AI081625]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI081625, R21AI127249] Funding Source: NIH RePORTER
In 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.
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