Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption

Thembi Mdluli; Bonnie M. Slike; Daniel J. Curtis; Zhanna Shubin; Ursula Tran; Yifan Li; Vincent Dussupt; Letzibeth Mendez-Rivera; Suteeraporn Pinyakorn; Daniel J. Stieh; Frank L. Tomaka; Hanneke Schuitemaker; Maria G. Pau; Donn J. Colby; Eugène Kroon; Carlo Sacdalan; Mark de Souza; Nittaya Phanupak; Denise C. Hsu; Jintanat Ananworanich; Julie A. Ake; Lydie Trautmann; Sandhya Vasan; Merlin L. Robb; Shelly J. Krebs; Dominic Paquin-Proulx; Morgane Rolland

doi:10.1016/j.celrep.2024.114344

Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption

Thembi Mdluli, Bonnie M. Slike, Daniel J. Curtis, Zhanna Shubin, Ursula Tran, Yifan Li, Vincent Dussupt, Letzibeth Mendez-Rivera, Suteeraporn Pinyakorn, Daniel J. Stieh, Frank L. Tomaka, Hanneke Schuitemaker, Maria G. Pau, Donn J. Colby, Eugène Kroon, Carlo Sacdalan, Mark de Souza, Nittaya Phanupak, Denise C. Hsu, Jintanat AnanworanichJulie A. Ake, Lydie Trautmann, Sandhya Vasan, Merlin L. Robb, Shelly J. Krebs, Dominic Paquin-Proulx, Morgane Rolland^*

^*Corresponding author for this work

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

Abstract

A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.

Original language	English
Article number	114344
Journal	Cell Reports
Volume	43
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2024.114344
State	Published - 25 Jun 2024
Externally published	Yes

Keywords

ADCP
CP: Immunology
CP: Microbiology
Fc effector responses
HIV-1
PLWH
acute infection
analytic treatment interruption
antibody responses
time to viral rebound
vaccine

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10.1016/j.celrep.2024.114344

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Mdluli, T., Slike, B. M., Curtis, D. J., Shubin, Z., Tran, U., Li, Y., Dussupt, V., Mendez-Rivera, L., Pinyakorn, S., Stieh, D. J., Tomaka, F. L., Schuitemaker, H., Pau, M. G., Colby, D. J., Kroon, E., Sacdalan, C., de Souza, M., Phanupak, N., Hsu, D. C., ... Rolland, M. (2024). Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption. Cell Reports, 43(6), Article 114344. https://doi.org/10.1016/j.celrep.2024.114344

@article{9e3a07abb8604a49b89d20d9727768aa,

title = "Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption",

abstract = "A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.",

keywords = "ADCP, CP: Immunology, CP: Microbiology, Fc effector responses, HIV-1, PLWH, acute infection, analytic treatment interruption, antibody responses, time to viral rebound, vaccine",

author = "Thembi Mdluli and Slike, {Bonnie M.} and Curtis, {Daniel J.} and Zhanna Shubin and Ursula Tran and Yifan Li and Vincent Dussupt and Letzibeth Mendez-Rivera and Suteeraporn Pinyakorn and Stieh, {Daniel J.} and Tomaka, {Frank L.} and Hanneke Schuitemaker and Pau, {Maria G.} and Colby, {Donn J.} and Eug{\`e}ne Kroon and Carlo Sacdalan and {de Souza}, Mark and Nittaya Phanupak and Hsu, {Denise C.} and Jintanat Ananworanich and Ake, {Julie A.} and Lydie Trautmann and Sandhya Vasan and Robb, {Merlin L.} and Krebs, {Shelly J.} and Dominic Paquin-Proulx and Morgane Rolland",

note = "Publisher Copyright: {\textcopyright} 2024 Henry M Jackson Foundation for the Advancement of Military Medicine, Inc",

year = "2024",

month = jun,

day = "25",

doi = "10.1016/j.celrep.2024.114344",

language = "English",

volume = "43",

journal = "Cell Reports",

issn = "2211-1247",

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Mdluli, T, Slike, BM, Curtis, DJ, Shubin, Z, Tran, U, Li, Y, Dussupt, V, Mendez-Rivera, L, Pinyakorn, S, Stieh, DJ, Tomaka, FL, Schuitemaker, H, Pau, MG, Colby, DJ, Kroon, E, Sacdalan, C, de Souza, M, Phanupak, N, Hsu, DC, Ananworanich, J, Ake, JA, Trautmann, L, Vasan, S, Robb, ML, Krebs, SJ, Paquin-Proulx, D & Rolland, M 2024, 'Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption', Cell Reports, vol. 43, no. 6, 114344. https://doi.org/10.1016/j.celrep.2024.114344

TY - JOUR

T1 - Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption

AU - Mdluli, Thembi

AU - Slike, Bonnie M.

AU - Curtis, Daniel J.

AU - Shubin, Zhanna

AU - Tran, Ursula

AU - Li, Yifan

AU - Dussupt, Vincent

AU - Mendez-Rivera, Letzibeth

AU - Pinyakorn, Suteeraporn

AU - Stieh, Daniel J.

AU - Tomaka, Frank L.

AU - Schuitemaker, Hanneke

AU - Pau, Maria G.

AU - Colby, Donn J.

AU - Kroon, Eugène

AU - Sacdalan, Carlo

AU - de Souza, Mark

AU - Phanupak, Nittaya

AU - Hsu, Denise C.

AU - Ananworanich, Jintanat

AU - Ake, Julie A.

AU - Trautmann, Lydie

AU - Vasan, Sandhya

AU - Robb, Merlin L.

AU - Krebs, Shelly J.

AU - Paquin-Proulx, Dominic

AU - Rolland, Morgane

PY - 2024/6/25

Y1 - 2024/6/25

N2 - A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.

AB - A heterologous Ad26/MVA vaccine was given prior to an analytic treatment interruption (ATI) in people living with HIV-1 (mainly CRF01_AE) who initiated antiretroviral treatment (ART) during acute HIV-1. We investigate the impact of Ad26/MVA vaccination on antibody (Ab)-mediated immune responses and their effect on time to viral rebound. The vaccine mainly triggers vaccine-matched binding Abs while, upon viral rebound post ATI, infection-specific CRF01_AE binding Abs increase in all participants. Binding Abs are not associated with time to viral rebound. The Ad26/MVA mosaic vaccine profile consists of correlated non-CRF01_AE binding Ab and Fc effector features, with strong Ab-dependent cellular phagocytosis (ADCP) responses. CRF01_AE-specific ADCP responses (measured either prior to or post ATI) are significantly higher in individuals with delayed viral rebound. Our results suggest that vaccines eliciting cross-reactive responses with circulating viruses in a target population could be beneficial and that ADCP responses may play a role in viral control post treatment interruption.

KW - ADCP

KW - CP: Immunology

KW - CP: Microbiology

KW - Fc effector responses

KW - HIV-1

KW - PLWH

KW - acute infection

KW - analytic treatment interruption

KW - antibody responses

KW - time to viral rebound

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85195165191&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2024.114344

DO - 10.1016/j.celrep.2024.114344

M3 - Article

C2 - 38850529

AN - SCOPUS:85195165191

SN - 2211-1247

VL - 43

JO - Cell Reports

JF - Cell Reports

IS - 6

M1 - 114344

ER -

Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption

Abstract

Keywords

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