Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children

Julia Roider; J. Zachary Porterfield; Paul Ogongo; Maximilian Muenchhoff; Emily Adland; Andreas Groll; Lynn Morris; Penny L. Moore; Thumbi Ndung'U; Henrik Kløverpris; Philip J.R. Goulder; Alasdair Leslie

doi:10.3389/fimmu.2019.01497

Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children

Julia Roider, J. Zachary Porterfield, Paul Ogongo, Maximilian Muenchhoff, Emily Adland, Andreas Groll, Lynn Morris, Penny L. Moore, Thumbi Ndung'U, Henrik Kløverpris, Philip J.R. Goulder, Alasdair Leslie^*

^*Corresponding author for this work

4 Citations (Scopus)

31 Downloads (Pure)

Abstract

Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group.

Original language	English
Article number	1497
Journal	Frontiers in Immunology
Volume	10
Issue number	JUL
Number of pages	9
ISSN	1664-3224
DOIs	https://doi.org/10.3389/fimmu.2019.01497
Publication status	Published - 2019

Keywords

Activin A
Broadly neutralizing antibodies (bnAbs)
CXCL13
HIV neutralization breadth
IL-5
Pediatric HIV
Plasma markers
T-follicular helper cells (Tfh)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected ChildrenFinal published version, 844 KBLicence: CC BY

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@article{382697bf295c457697f2247c4171a96b,

title = "Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children",

abstract = "Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group.",

keywords = "Activin A, Broadly neutralizing antibodies (bnAbs), CXCL13, HIV neutralization breadth, IL-5, Pediatric HIV, Plasma markers, T-follicular helper cells (Tfh)",

author = "Julia Roider and {Zachary Porterfield}, J. and Paul Ogongo and Maximilian Muenchhoff and Emily Adland and Andreas Groll and Lynn Morris and Moore, {Penny L.} and Thumbi Ndung'U and Henrik Kl{\o}verpris and Goulder, {Philip J.R.} and Alasdair Leslie",

year = "2019",

doi = "10.3389/fimmu.2019.01497",

language = "English",

volume = "10",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Research Foundation",

number = "JUL",

}

TY - JOUR

T1 - Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children

AU - Roider, Julia

AU - Zachary Porterfield, J.

AU - Ogongo, Paul

AU - Muenchhoff, Maximilian

AU - Adland, Emily

AU - Groll, Andreas

AU - Morris, Lynn

AU - Moore, Penny L.

AU - Ndung'U, Thumbi

AU - Kløverpris, Henrik

AU - Goulder, Philip J.R.

AU - Leslie, Alasdair

PY - 2019

Y1 - 2019

N2 - Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group.

AB - Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group.

KW - Activin A

KW - Broadly neutralizing antibodies (bnAbs)

KW - CXCL13

KW - HIV neutralization breadth

KW - IL-5

KW - Pediatric HIV

KW - Plasma markers

KW - T-follicular helper cells (Tfh)

U2 - 10.3389/fimmu.2019.01497

DO - 10.3389/fimmu.2019.01497

M3 - Journal article

C2 - 31333650

AN - SCOPUS:85069036439

SN - 1664-3224

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

IS - JUL

M1 - 1497

ER -

Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children

Abstract

Keywords

UN SDGs

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