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

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

doi:https://doi.org/10.1016/j.celrep.2016.10.085

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

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

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

128 Citations (Scopus)

Abstract

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

Original language	English
Pages (from-to)	2195-2209
Journal	Cell reports
Volume	17
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2016.10.085
Publication status	Published - 2016

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https://doi.org/10.1016/j.celrep.2016.10.085

Cite this

Havenar-Daughton, C., Carnathan, D. G., Torrents de la Peña, A., Pauthner, M., Briney, B., Reiss, S. M., Wood, J. S., Kaushik, K., van Gils, M. J., Rosales, S. L., van der Woude, P., Locci, M., Le, K. M., de Taeye, S. W., Sok, D., Mohammed, A. U. R., Huang, J., Gumber, S., Garcia, A., ... Crotty, S. (2016). Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer. Cell reports, 17(9), 2195-2209. https://doi.org/10.1016/j.celrep.2016.10.085

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

abstract = "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",

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

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Havenar-Daughton, C, Carnathan, DG, Torrents de la Peña, A, Pauthner, M, Briney, B, Reiss, SM, Wood, JS, Kaushik, K, van Gils, MJ, Rosales, SL, van der Woude, P, Locci, M, Le, KM, de Taeye, SW, Sok, D, Mohammed, AUR, Huang, J, Gumber, S, Garcia, A, Kasturi, SP, Pulendran, B, Moore, JP, Ahmed, R, Seumois, G, Burton, DR, Sanders, RW, Silvestri, G & Crotty, S 2016, 'Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer', Cell reports, vol. 17, no. 9, pp. 2195-2209. https://doi.org/10.1016/j.celrep.2016.10.085

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T1 - Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer

AU - Havenar-Daughton, Colin

AU - Carnathan, Diane G.

AU - Torrents de la Peña, Alba

AU - Pauthner, Matthias

AU - Briney, Bryan

AU - Reiss, Samantha M.

AU - Wood, Jennifer S.

AU - Kaushik, Kirti

AU - van Gils, Marit J.

AU - Rosales, Sandy L.

AU - van der Woude, Patricia

AU - Locci, Michela

AU - Le, Khoa M.

AU - de Taeye, Steven W.

AU - Sok, Devin

AU - Mohammed, Ata Ur Rasheed

AU - Huang, Jessica

AU - Gumber, Sanjeev

AU - Garcia, AnaPatricia

AU - Kasturi, Sudhir P.

AU - Pulendran, Bali

AU - Moore, John P.

AU - Ahmed, Rafi

AU - Seumois, Grégory

AU - Burton, Dennis R.

AU - Sanders, Rogier W.

AU - Silvestri, Guido

AU - Crotty, Shane

PY - 2016

Y1 - 2016

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/j.celrep.2016.10.085

DO - https://doi.org/10.1016/j.celrep.2016.10.085

M3 - Article

C2 - 27880897

SN - 2211-1247

VL - 17

SP - 2195

EP - 2209

JO - Cell reports

JF - Cell reports

IS - 9

ER -