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Review
. 2017 Jan;275(1):79-88.
doi: 10.1111/imr.12508.

Host controls of HIV broadly neutralizing antibody development

Garnett Kelsoe  1 , Barton F Haynes  1
Affiliations
Review

Host controls of HIV broadly neutralizing antibody development

Garnett Kelsoe et al. Immunol Rev. 2017 Jan.

Abstract

Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been made recently in understanding host immunologic controls of bNAb induction and maturation in the setting of HIV infection, and point to key roles for both central and peripheral immunologic tolerance mechanisms in limiting bnAb development. Immune tolerance checkpoint inhibition has been transformative in promotion of anti-tumor CD8 T-cell responses in the treatment of certain malignancies. Here, we review the evidence for host controls of bNAb responses, and discuss strategies for the transient modulation of immune responses with vaccines toward the goal of enhancing germinal center B-cell responses to favor bNAb B-cell lineages and to foster their maturation to full neutralization potency.

Keywords: AIDS; B cells; autoantibodies; autoimmunity; vaccination.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors certify that they have no conflict of interest with regard to the content and conclusions of this manuscript.

Figures

FIGURE 1
FIGURE 1
UBE3A is a shared autoantigen by 4 CD4bs bNAbs. UBE3A was recognized by VRC01, VRC02, CH106, and CH103 with varying strengths in protein array, and ELISA. (A) Representative protein array summary for protein arrays blotted with CD4bs bNAbs VRC01, VRC02, CH106, CH103, or 151K control. Axis values are fluorescence intensity in 151 array (y-axis) or bNAb array (x-axis). Each dot is the average MFI of duplicate proteins. Major diagonal is equal binding by test Ab and 151K. Dashed line indicates 500-fold MFI threshold to define strong autoreactivity. UBE3A proteins circled. (B) CD4bs bNAb (circle), and 151K (triangle) were tested for binding to UBE3A in sandwich ELISA under stringent conditions. Used with permission
FIGURE 2
FIGURE 2
Chloroquine rescues B-cell development in 2F5 knockin mice. 2F5 mice were injected with PBS or chloroquine for 2 weeks and then killed. B-cell frequencies in bone marrow and spleen were then determined by FACS. Chloroquine increased the frequency of immature and T1 B cells in bone marrow, T1 and T2 B cells in spleen (upper row), and in the mature splenic MZ, and MF B cell compartments (lower row)
See this image and copyright information in PMC

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