Abstract
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.
Highlights
Natural immunity to many viral diseases relies upon circulating neutralizing antibodies from long-lived plasma cells in the bone marrow or the production of neutralizing antibodies from memory B cells after re-activation by the infecting pathogen, frequently years afterThis article is part of a series of reviews covering B cells and Immunity to HIV appearing in Volume 275 of Immunological Reviews.the original exposure
We found that virus produced in the presence of kifunensine, resulting in untrimmed high-mannose glycans, is not neutralized by PG9/16.66 These bnAbs are sensitive to natural glycan heterogeneity, which means a fraction of virions may be resistant to neutralization because they contain glycoforms that are not recognized by the Abs, resulting in incomplete neutralization curves.[66]
Given the great progress over the past decade in isolating bnAbs and studying their modes of action, an obvious question is do we still need more bnAbs? The more recent discovery and characterization of gp120-gp[41] interface bnAbs suggest it is still worthwhile to search for new bnAbs because they could reveal novel sites of vulnerability on envelope protein (Env)
Summary
Natural immunity to many viral diseases relies upon circulating neutralizing antibodies from long-lived plasma cells in the bone marrow or the production of neutralizing antibodies from memory B cells after re-activation by the infecting pathogen, frequently years afterThis article is part of a series of reviews covering B cells and Immunity to HIV appearing in Volume 275 of Immunological Reviews.the original exposure.
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