Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity

Miriam Rosás-Umbert; Jesper D. Gunst; Marie H. Pahus; Rikke Olesen; Mariane Schleimann; Paul W. Denton; Victor Ramos; Adam Ward; Natalie N. Kinloch; Dennis C. Copertino; Tuixent Escribà; Anuska Llano; Zabrina L. Brumme; R. Brad Jones; Beatriz Mothe; Christian Brander; Julie Fox; Michel C. Nussenzweig; Sarah Fidler; Marina Caskey; Martin Tolstrup; Ole S. Søgaard

doi:10.1038/s41467-022-34171-2

Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8⁺ T cell immunity

Miriam Rosás-Umbert, Jesper D. Gunst, Marie H. Pahus, Rikke Olesen, Mariane Schleimann, Paul W. Denton, Victor Ramos, Adam Ward, Natalie N. Kinloch, Dennis C. Copertino, Tuixent Escribà, Anuska Llano, Zabrina L. Brumme, R. Brad Jones, Beatriz Mothe, Christian Brander, Julie Fox, Michel C. Nussenzweig, Sarah Fidler, Marina CaskeyMartin Tolstrup, Ole S. Søgaard^*

^*Corresponding author for this work

Department of Clinical Medicine - Department of Infectious Diseases

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

36 Citations (Scopus)

Abstract

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8⁺ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8⁺ T cell responses that are associated with ART-free virologic control.

Original language	English
Article number	6473
Journal	Nature Communications
Volume	13
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-022-34171-2
Publication status	Published - Oct 2022

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Rosás-Umbert, M., Gunst, J. D., Pahus, M. H., Olesen, R., Schleimann, M., Denton, P. W., Ramos, V., Ward, A., Kinloch, N. N., Copertino, D. C., Escribà, T., Llano, A., Brumme, Z. L., Brad Jones, R., Mothe, B., Brander, C., Fox, J., Nussenzweig, M. C., Fidler, S., ... Søgaard, O. S. (2022). Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8⁺ T cell immunity. Nature Communications, 13, Article 6473. https://doi.org/10.1038/s41467-022-34171-2

@article{cb5326f6ac234d4bbc5d5b9bb7495fbf,

title = "Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity",

abstract = "In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control.",

author = "Miriam Ros{\'a}s-Umbert and Gunst, {Jesper D.} and Pahus, {Marie H.} and Rikke Olesen and Mariane Schleimann and Denton, {Paul W.} and Victor Ramos and Adam Ward and Kinloch, {Natalie N.} and Copertino, {Dennis C.} and Tuixent Escrib{\`a} and Anuska Llano and Brumme, {Zabrina L.} and {Brad Jones}, R. and Beatriz Mothe and Christian Brander and Julie Fox and Nussenzweig, {Michel C.} and Sarah Fidler and Marina Caskey and Martin Tolstrup and S{\o}gaard, {Ole S.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = oct,

doi = "10.1038/s41467-022-34171-2",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

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Rosás-Umbert, M , Gunst, JD , Pahus, MH , Olesen, R , Schleimann, M, Denton, PW, Ramos, V, Ward, A, Kinloch, NN, Copertino, DC, Escribà, T, Llano, A, Brumme, ZL, Brad Jones, R, Mothe, B, Brander, C, Fox, J, Nussenzweig, MC, Fidler, S, Caskey, M, Tolstrup, M & Søgaard, OS 2022, 'Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8⁺ T cell immunity', Nature Communications, vol. 13, 6473. https://doi.org/10.1038/s41467-022-34171-2

Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8⁺ T cell immunity. / Rosás-Umbert, Miriam ; Gunst, Jesper D.; Pahus, Marie H. et al.
In: Nature Communications, Vol. 13, 6473, 10.2022.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity

AU - Rosás-Umbert, Miriam

AU - Gunst, Jesper D.

AU - Pahus, Marie H.

AU - Olesen, Rikke

AU - Schleimann, Mariane

AU - Denton, Paul W.

AU - Ramos, Victor

AU - Ward, Adam

AU - Kinloch, Natalie N.

AU - Copertino, Dennis C.

AU - Escribà, Tuixent

AU - Llano, Anuska

AU - Brumme, Zabrina L.

AU - Brad Jones, R.

AU - Mothe, Beatriz

AU - Brander, Christian

AU - Fox, Julie

AU - Nussenzweig, Michel C.

AU - Fidler, Sarah

AU - Caskey, Marina

AU - Tolstrup, Martin

AU - Søgaard, Ole S.

PY - 2022/10

Y1 - 2022/10

N2 - In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control.

AB - In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control.

UR - http://www.scopus.com/inward/record.url?scp=85140927548&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-34171-2

DO - 10.1038/s41467-022-34171-2

M3 - Journal article

C2 - 36309514

AN - SCOPUS:85140927548

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

M1 - 6473

ER -

Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8⁺ T cell immunity

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