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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Roider J,Porterfield JZ,Ogongo P,Muenchhoff M,Adland E,Groll A,Morris L,Moore PL,Ndung'u T,Kløverpris H,Goulder PJR,Leslie Adoi
10.3389/fimmu.2019.01497subject
Has Abstractpub_date
2019-07-02 00:00:00pages
1497issn
1664-3224journal_volume
10pub_type
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