Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

Godelieve J. de Bree; Adam K. Wheatley; Rebecca M. Lynch; Madhu Prabhakaran; Marlous L. Grijsen; Jan M. Prins; Stephen D. Schmidt; Richard A. Koup; John R. Mascola; Adrian B. McDermott

doi:https://doi.org/10.1371/journal.pone.0173577

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

Godelieve J. de Bree, Adam K. Wheatley, Rebecca M. Lynch, Madhu Prabhakaran, Marlous L. Grijsen, Jan M. Prins, Stephen D. Schmidt, Richard A. Koup, John R. Mascola, Adrian B. McDermott

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4 Citations (Scopus)

Abstract

Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks. Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment. At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point. These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients

Original language	English
Pages (from-to)	e0173577
Journal	PLOS ONE
Volume	12
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0173577
Publication status	Published - 2017

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https://doi.org/10.1371/journal.pone.0173577

Cite this

@article{e4193d88b0a642e1bf0a5bc920f38941,

title = "Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection",

abstract = "Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks. Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment. At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point. These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients",

author = "{de Bree}, {Godelieve J.} and Wheatley, {Adam K.} and Lynch, {Rebecca M.} and Madhu Prabhakaran and Grijsen, {Marlous L.} and Prins, {Jan M.} and Schmidt, {Stephen D.} and Koup, {Richard A.} and Mascola, {John R.} and McDermott, {Adrian B.}",

year = "2017",

doi = "https://doi.org/10.1371/journal.pone.0173577",

language = "English",

volume = "12",

pages = "e0173577",

journal = "PLOS ONE",

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number = "3",

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T1 - Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

AU - de Bree, Godelieve J.

AU - Wheatley, Adam K.

AU - Lynch, Rebecca M.

AU - Prabhakaran, Madhu

AU - Grijsen, Marlous L.

AU - Prins, Jan M.

AU - Schmidt, Stephen D.

AU - Koup, Richard A.

AU - Mascola, John R.

AU - McDermott, Adrian B.

PY - 2017

Y1 - 2017

N2 - Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks. Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment. At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point. These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients

AB - Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks. Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment. At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point. These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients

U2 - https://doi.org/10.1371/journal.pone.0173577

DO - https://doi.org/10.1371/journal.pone.0173577

M3 - Article

C2 - 28296911

SN - 1932-6203

VL - 12

SP - e0173577

JO - PLOS ONE

JF - PLOS ONE

IS - 3

ER -