Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics

Alexandra Tauzin; Lorie Marchitto; Étienne Bélanger; Mehdi Benlarbi; Guillaume Beaudoin-Bussières; Jérémie Prévost; Derek Yang; Ta-Jung Chiu; Hung-Ching Chen; Catherine Bourassa; Halima Medjahed; Marek K Korzeniowski; Suneetha Gottumukkala; William D Tolbert; Jonathan Richard; Amos B Smith; Marzena Pazgier; Andrés Finzi

doi:10.1101/2024.06.02.24308281

Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics

Alexandra Tauzin, Lorie Marchitto, Étienne Bélanger, Mehdi Benlarbi, Guillaume Beaudoin-Bussières, Jérémie Prévost, Derek Yang, Ta-Jung Chiu, Hung-Ching Chen, Catherine Bourassa, Halima Medjahed, Marek K Korzeniowski, Suneetha Gottumukkala, William D Tolbert, Jonathan Richard, Amos B Smith, Marzena Pazgier, Andrés Finzi

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

Abstract

CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation which occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in presence of CD4mc.

Original language	English
Journal	medrxiv
DOIs	https://doi.org/10.1101/2024.06.02.24308281
State	Published - 4 Jun 2024

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10.1101/2024.06.02.24308281

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Tauzin, A., Marchitto, L., Bélanger, É., Benlarbi, M., Beaudoin-Bussières, G., Prévost, J., Yang, D., Chiu, T.-J., Chen, H.-C., Bourassa, C., Medjahed, H., Korzeniowski, M. K., Gottumukkala, S., Tolbert, W. D., Richard, J., Smith, A. B., Pazgier, M., & Finzi, A. (2024). Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics. medrxiv. https://doi.org/10.1101/2024.06.02.24308281

@article{4717dc4f850c4a9ea3593327eec5b71d,

title = "Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics",

abstract = "CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a {"}closed{"} conformation which occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in presence of CD4mc.",

author = "Alexandra Tauzin and Lorie Marchitto and {\'E}tienne B{\'e}langer and Mehdi Benlarbi and Guillaume Beaudoin-Bussi{\`e}res and J{\'e}r{\'e}mie Pr{\'e}vost and Derek Yang and Ta-Jung Chiu and Hung-Ching Chen and Catherine Bourassa and Halima Medjahed and Korzeniowski, {Marek K} and Suneetha Gottumukkala and Tolbert, {William D} and Jonathan Richard and Smith, {Amos B} and Marzena Pazgier and Andr{\'e}s Finzi",

year = "2024",

month = jun,

day = "4",

doi = "10.1101/2024.06.02.24308281",

language = "English",

journal = "medrxiv",

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Tauzin, A, Marchitto, L, Bélanger, É, Benlarbi, M, Beaudoin-Bussières, G, Prévost, J, Yang, D, Chiu, T-J, Chen, H-C, Bourassa, C, Medjahed, H, Korzeniowski, MK, Gottumukkala, S, Tolbert, WD, Richard, J, Smith, AB, Pazgier, M & Finzi, A 2024, 'Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics', medrxiv. https://doi.org/10.1101/2024.06.02.24308281

TY - JOUR

T1 - Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in presence of CD4-mimetics

AU - Tauzin, Alexandra

AU - Marchitto, Lorie

AU - Bélanger, Étienne

AU - Benlarbi, Mehdi

AU - Beaudoin-Bussières, Guillaume

AU - Prévost, Jérémie

AU - Yang, Derek

AU - Chiu, Ta-Jung

AU - Chen, Hung-Ching

AU - Bourassa, Catherine

AU - Medjahed, Halima

AU - Korzeniowski, Marek K

AU - Gottumukkala, Suneetha

AU - Tolbert, William D

AU - Richard, Jonathan

AU - Smith, Amos B

AU - Pazgier, Marzena

AU - Finzi, Andrés

PY - 2024/6/4

Y1 - 2024/6/4

N2 - CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation which occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in presence of CD4mc.

AB - CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation which occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in presence of CD4mc.

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DO - 10.1101/2024.06.02.24308281

M3 - Article

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JO - medrxiv

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