Details

Autor(en) / Beteiligte

• Havenar-Daughton, Colin
• Carnathan, Diane G.
• Torrents de la Peña, Alba
• Pauthner, Matthias
• Briney, Bryan
• Reiss, Samantha M.
• Wood, Jennifer S.
• Kaushik, Kirti
• van Gils, Marit J.
• Rosales, Sandy L.
• van der Woude, Patricia
• Locci, Michela
• Le, Khoa M.
• de Taeye, Steven W.
• Sok, Devin
• Mohammed, Ata Ur Rasheed
• Huang, Jessica
• Gumber, Sanjeev
• Garcia, AnaPatricia
• Kasturi, Sudhir P.
• Pulendran, Bali
• Moore, John P.
• Ahmed, Rafi
• Seumois, Grégory
• Burton, Dennis R.
• Sanders, Rogier W.
• Silvestri, Guido
• Crotty, Shane

Titel

Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer

Ist Teil von

• Cell reports (Cambridge), 2016-11, Vol.17 (9), p.2195-2209

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Generating tier 2 HIV-neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses with Env immunogens remain unclear. Here, some rhesus monkeys developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2) whereas others did not. This was not because HIV Env trimers were immunologically silent because all monkeys made similar ELISA-binding antibody responses; the key difference was nAb versus non-nAb responses. We explored the immunological barriers to HIV nAb responses by combining a suite of techniques, including longitudinal lymph node fine needle aspirates. Unexpectedly, nAb development best correlated with booster immunization GC B cell magnitude and Tfh characteristics of the Env-specific CD4 T cells. Notably, these factors distinguished between successful and unsuccessful antibody responses because GC B cell frequencies and stoichiometry to GC Tfh cells correlated with nAb development, but did not correlate with total Env Ab binding titers. [Display omitted] •Fine needle aspirates quantitatively monitor germinal center activity in lymph nodes•Neutralizing antibodies correlate with GC B cell magnitude, not ELISA Ab titers•Tfh cell quality is associated with vaccine-elicited HIV-neutralizing antibodies•LN FNA probing of GCs should be an immune correlate in HIV vaccine trials This study explores the immunological process by which a protein vaccine elicits HIV-neutralizing antibodies. Using direct probing of lymph nodes, Havenar-Daughton et al. show that neutralizing antibody development correlates with germinal center B cell frequencies and Tfh cells and that those responses can be tracked by LN FNAs over time.