Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals

Csaba Fehér; Roque Pastor-Lbáñez; Lorna Leal; Montserrat Plana; Mireia Arnedo; Henk Jan van den Ham; Arno C. Andeweg; Rob A. Gruters; Francisco Díez-Fuertes; José Alcamí; Patrick Aloy; Felipe García

doi:10.3390/vaccines9070799

Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals

Csaba Fehér^*, Roque Pastor-Lbáñez, Lorna Leal, Montserrat Plana, Mireia Arnedo, Henk Jan van den Ham, Arno C. Andeweg, Rob A. Gruters, Francisco Díez-Fuertes, José Alcamí, Patrick Aloy, Felipe García

^*Corresponding author for this work

Virology

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

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Abstract

Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene ‘signatures’ that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were extracted from frozen post-vaccination PBMC samples; gene expression was determined by microarray method. In gene set enrichment analysis, responders showed an up-regulation of 14 gene sets (TNF-alpha/NFkB pathway, inflammatory response, the complement system, Il6 and Il2 JAK-STAT signaling, among others) and a down-regulation of 7 gene sets (such as E2F targets or interferon alpha response). The expression of genes regulated by three (miR-223-3p, miR-1183 and miR-8063) of the 9 differentially expressed miRNAs was significantly down-regulated in responders. The deregulation of certain gene sets related to inflammatory processes seems fundamental for viral control, and certain miRNAs may be important in fine-tuning these processes.

Original language	English
Article number	799
Journal	Vaccines
Volume	9
Issue number	7
DOIs	https://doi.org/10.3390/vaccines9070799
Publication status	Published - 19 Jul 2021

Bibliographical note

Funding Information:
Funding: This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018-096309-B-I00), the Fondo de Investigación Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Program/Generalitat de Catalunya SGR 615. F.G. has received the support of José María Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study.

Funding Information:
This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018096309-B-I00), the Fondo de Investigación Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Pro-gram/Generalitat de Catalunya SGR 615. F.G. has received the support of José María Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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Fehér, C., Pastor-Lbáñez, R., Leal, L., Plana, M., Arnedo, M., van den Ham, H. J., Andeweg, A. C., Gruters, R. A., Díez-Fuertes, F., Alcamí, J., Aloy, P., & García, F. (2021). Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals. Vaccines, 9(7), [799]. https://doi.org/10.3390/vaccines9070799

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title = "Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals",

abstract = "Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene {\textquoteleft}signatures{\textquoteright} that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were extracted from frozen post-vaccination PBMC samples; gene expression was determined by microarray method. In gene set enrichment analysis, responders showed an up-regulation of 14 gene sets (TNF-alpha/NFkB pathway, inflammatory response, the complement system, Il6 and Il2 JAK-STAT signaling, among others) and a down-regulation of 7 gene sets (such as E2F targets or interferon alpha response). The expression of genes regulated by three (miR-223-3p, miR-1183 and miR-8063) of the 9 differentially expressed miRNAs was significantly down-regulated in responders. The deregulation of certain gene sets related to inflammatory processes seems fundamental for viral control, and certain miRNAs may be important in fine-tuning these processes.",

author = "Csaba Feh{\'e}r and Roque Pastor-Lb{\'a}{\~n}ez and Lorna Leal and Montserrat Plana and Mireia Arnedo and {van den Ham}, {Henk Jan} and Andeweg, {Arno C.} and Gruters, {Rob A.} and Francisco D{\'i}ez-Fuertes and Jos{\'e} Alcam{\'i} and Patrick Aloy and Felipe Garc{\'i}a",

note = "Funding Information: Funding: This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018-096309-B-I00), the Fondo de Investigaci{\'o}n Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Program/Generalitat de Catalunya SGR 615. F.G. has received the support of Jos{\'e} Mar{\'i}a Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study. Funding Information: This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018096309-B-I00), the Fondo de Investigaci{\'o}n Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Pro-gram/Generalitat de Catalunya SGR 615. F.G. has received the support of Jos{\'e} Mar{\'i}a Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/vaccines9070799",

language = "English",

volume = "9",

journal = "Vaccines",

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Fehér, C, Pastor-Lbáñez, R, Leal, L, Plana, M, Arnedo, M, van den Ham, HJ, Andeweg, AC, Gruters, RA, Díez-Fuertes, F, Alcamí, J, Aloy, P & García, F 2021, 'Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals', Vaccines, vol. 9, no. 7, 799. https://doi.org/10.3390/vaccines9070799

TY - JOUR

T1 - Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals

AU - Fehér, Csaba

AU - Pastor-Lbáñez, Roque

AU - Leal, Lorna

AU - Plana, Montserrat

AU - Arnedo, Mireia

AU - van den Ham, Henk Jan

AU - Andeweg, Arno C.

AU - Gruters, Rob A.

AU - Díez-Fuertes, Francisco

AU - Alcamí, José

AU - Aloy, Patrick

AU - García, Felipe

N1 - Funding Information: Funding: This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018-096309-B-I00), the Fondo de Investigación Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Program/Generalitat de Catalunya SGR 615. F.G. has received the support of José María Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study. Funding Information: This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018096309-B-I00), the Fondo de Investigación Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Pro-gram/Generalitat de Catalunya SGR 615. F.G. has received the support of José María Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/7/19

Y1 - 2021/7/19

N2 - Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene ‘signatures’ that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were extracted from frozen post-vaccination PBMC samples; gene expression was determined by microarray method. In gene set enrichment analysis, responders showed an up-regulation of 14 gene sets (TNF-alpha/NFkB pathway, inflammatory response, the complement system, Il6 and Il2 JAK-STAT signaling, among others) and a down-regulation of 7 gene sets (such as E2F targets or interferon alpha response). The expression of genes regulated by three (miR-223-3p, miR-1183 and miR-8063) of the 9 differentially expressed miRNAs was significantly down-regulated in responders. The deregulation of certain gene sets related to inflammatory processes seems fundamental for viral control, and certain miRNAs may be important in fine-tuning these processes.

AB - Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene ‘signatures’ that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were extracted from frozen post-vaccination PBMC samples; gene expression was determined by microarray method. In gene set enrichment analysis, responders showed an up-regulation of 14 gene sets (TNF-alpha/NFkB pathway, inflammatory response, the complement system, Il6 and Il2 JAK-STAT signaling, among others) and a down-regulation of 7 gene sets (such as E2F targets or interferon alpha response). The expression of genes regulated by three (miR-223-3p, miR-1183 and miR-8063) of the 9 differentially expressed miRNAs was significantly down-regulated in responders. The deregulation of certain gene sets related to inflammatory processes seems fundamental for viral control, and certain miRNAs may be important in fine-tuning these processes.

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DO - 10.3390/vaccines9070799

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VL - 9

JO - Vaccines

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ER -

Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals

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