Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01104
Keywords
B-cell subsets; acute HIV; CXCL13; cross-neutralizing antibodies; BAFF
Categories
Funding
- National Institute of Health [R37 AI080289-06A1, R01 102660-01]
- Bill and Melinda Gates Foundation CAVD [OPP1032817]
- Ragon Institute of MGH, MIT and Harvard
- International AIDS Vaccine Initiative (IAVI) [UKZNRSA1001]
- South African Research Chairs Initiative [64809]
- Victor Daitz Foundation
- Howard Hughes Medical Institute [55007427]
- Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [DEL-15-006]
- New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency)
- Wellcome Trust [107752/Z/15/Z]
- United Kingdom (UK) government
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Immunological events in acute HIV-1 infection before peak viremia (hyperacute phase) may contribute to the development of broadly cross-neutralizing antibodies. Here, we used pre-infection and acute-infection peripheral blood mononuclear cells and plasma samples from 22 women, including 10 who initiated antiretroviral treatment in Fiebig stages I-V of acute infection to study B cell subsets and B-cell associated cytokines (BAFF and CXCL13) kinetics for up to similar to 90 days post detection of plasma viremia. Frequencies of B cell subsets were defined by flow cytometry while plasma cytokine levels were measured by ELISA. We observed a rapid but transient increase in exhausted tissue-like memory, activated memory, and plasmablast B cells accompanied by decline in resting memory cells in untreated, but not treated women. B cell subset frequencies in untreated women positively correlated with viral loads but did not predict emergence of cross-neutralizing antibodies measured 12 months post detection of plasma viremia. Plasma BAFF and CXCL13 levels increased only in untreated women, but their levels did not correlate with viral loads. Importantly, early CXCL13 but not BAFF levels predicted the later emergence of detectable cross-neutralizing antibodies at 12 months post detection of plasma viremia. Thus, hyperacute HIV-1 infection is associated with B cell subset changes, which do not predict emergence of cross-neutralizing antibodies. However, plasma CXCL13 levels during hyperacute infection predicted the subsequent emergence of cross-neutralizing antibodies, providing a potential biomarker for the evaluation of vaccines designed to elicit cross-neutralizing activity or for natural infection studies to explore mechanisms underlying development of neutralizing antibodies.
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