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

Microbiology, Immunology, and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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
DOIs	https://doi.org/10.3389/fimmu.2019.01497
State	Published - 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 Roider, Porterfield, Ogongo, Muenchhoff, Adland, Groll, Morris, Moore, Ndung'u, Kløverpris, Goulder and Leslie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funding

AL is funded through the Wellcome Trust (grant 210662/Z/18/Z) and HHMI. PG is funded through the Wellcome Trust (grant 104748MA). HK is funded through the Wellcome Trust (grant 202485/Z/16/Z). PM is supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant 98341). This work was partially funded through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant 07752/Z/15/Z) and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government. AL is funded through the Wellcome Trust (grant 210662/Z/18/Z) and HHMI. PG is funded through the Wellcome Trust (grant 104748MA). HK is funded through the Wellcome Trust (grant 202485/Z/16/Z). PM is supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant 98341). This work was partially funded through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant 07752/Z/15/Z) and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government.

Funders	Funder number
African Academy of Sciences
Department of Science and Technology, Republic of South Africa
Department of Science and Technology, Ministry of Science and Technology, India
Delaware IDeA Network of Biomedical Research Excellence
Government of the United Kingdom
Wellcome Trust	210662/Z/18/Z, 202485
Howard Hughes Medical Institute	104748MA, 202485/Z/16/Z
National Research Foundation South African Research Chair	98341, DEL-15-006
New Partnership for Africa's Development	07752/Z/15/Z

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.3389/fimmu.2019.01497

Cite this

@article{2cbef2e97e2147da9b0e946c17301fda,

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.",

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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",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 Roider, Porterfield, Ogongo, Muenchhoff, Adland, Groll, Morris, Moore, Ndung'u, Kl{\o}verpris, Goulder and Leslie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",

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doi = "10.3389/fimmu.2019.01497",

language = "English",

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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

N1 - Publisher Copyright: Copyright © 2019 Roider, Porterfield, Ogongo, Muenchhoff, Adland, Groll, Morris, Moore, Ndung'u, Kløverpris, Goulder and Leslie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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.

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KW - Broadly neutralizing antibodies (bnAbs)

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KW - HIV neutralization breadth

KW - IL-5

KW - Pediatric HIV

KW - Plasma markers

KW - T-follicular helper cells (Tfh)

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DO - 10.3389/fimmu.2019.01497

M3 - Article

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JO - Frontiers in Immunology

JF - Frontiers in Immunology

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M1 - 1497

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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Cite this