Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children

• Published in: Frontiers in immunology 2019-07, Vol.10, p.1497
• Main Authors: Roider, Julia, Porterfield, J Zachary, Ogongo, Paul, Muenchhoff, Maximilian, Adland, Emily, Groll, Andreas, Morris, Lynn, Moore, Penny L, Ndung'u, Thumbi, Kløverpris, Henrik, Goulder, Philip J R, Leslie, Alasdair
• Format: Article
• Language: English
• Subjects: Activin A; Activins - blood; Adolescent; Biomarkers - blood; broadly neutralizing antibodies (bnAbs); Broadly Neutralizing Antibodies - immunology; Chemokine CXCL13 - blood; Child; Cohort Studies; CXCL13; Disease Progression; Germinal Center - immunology; HIV Antibodies - immunology; HIV Infections - blood; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; Humans; IL-5; Immunology; Interleukin-5 - blood; Neutralization Tests; pediatric HIV; plasma markers; T-Lymphocytes, Helper-Inducer - immunology; Viral Load
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.01497

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 (T ) with an effector phenotype, and the presence of IL-21 secreting HIV-specific T within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing T 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 T 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 T cells, it was not associated with effector T . 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.