Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial

Lucia Bailón; Anuska Llano; Samandhy Cedeño; Tuixent Escribà; Miriam Rosás-Umbert; Mariona Parera; Maria Casadellà; Miriam Lopez; Francisco Pérez; Bruna Oriol-Tordera; Marta Ruiz-Riol; Josep Coll; Felix Perez; Àngel Rivero; Anne R. Leselbaum; Ian McGowan; Devi Sengupta; Edmund G. Wee; Tomáš Hanke; Roger Paredes; Yovaninna Alarcón-Soto; Bonaventura Clotet; Marc Noguera-Julian; Christian Brander; the AELIX002 Study Group

doi:10.1038/s41591-022-02060-2

Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial

Lucia Bailón, Anuska Llano, Samandhy Cedeño, Tuixent Escribà, Miriam Rosás-Umbert, Mariona Parera, Maria Casadellà, Miriam Lopez, Francisco Pérez, Bruna Oriol-Tordera, Marta Ruiz-Riol, Josep Coll, Felix Perez, Àngel Rivero, Anne R. Leselbaum, Ian McGowan, Devi Sengupta, Edmund G. Wee, Tomáš Hanke, Roger ParedesYovaninna Alarcón-Soto, Bonaventura Clotet, Marc Noguera-Julian, Christian Brander, the AELIX002 Study Group

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

42 Citations (Scopus)

Abstract

HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml⁻¹, >10,000 copies ml⁻¹ for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials.

Original language	English
Journal	Nature Medicine
Volume	28
Issue	12
Pages (from-to)	2611-2621
Number of pages	11
ISSN	1078-8956
DOIs	https://doi.org/10.1038/s41591-022-02060-2
Publication status	Published - Dec 2022

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Bailón, L., Llano, A., Cedeño, S., Escribà, T., Rosás-Umbert, M., Parera, M., Casadellà, M., Lopez, M., Pérez, F., Oriol-Tordera, B., Ruiz-Riol, M., Coll, J., Perez, F., Rivero, À., Leselbaum, A. R., McGowan, I., Sengupta, D., Wee, E. G., Hanke, T., ... the AELIX002 Study Group (2022). Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. Nature Medicine, 28(12), 2611-2621. https://doi.org/10.1038/s41591-022-02060-2

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title = "Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial",

abstract = "HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml−1, >10,000 copies ml−1 for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials.",

author = "Lucia Bail{\'o}n and Anuska Llano and Samandhy Cede{\~n}o and Tuixent Escrib{\`a} and Miriam Ros{\'a}s-Umbert and Mariona Parera and Maria Casadell{\`a} and Miriam Lopez and Francisco P{\'e}rez and Bruna Oriol-Tordera and Marta Ruiz-Riol and Josep Coll and Felix Perez and {\`A}ngel Rivero and Leselbaum, {Anne R.} and Ian McGowan and Devi Sengupta and Wee, {Edmund G.} and Tom{\'a}{\v s} Hanke and Roger Paredes and Yovaninna Alarc{\'o}n-Soto and Bonaventura Clotet and Marc Noguera-Julian and Christian Brander and Jose Molto and Beatriz Mothe and Barriocanal, {Ana Mar{\'i}a} and Susana Benet and Patricia Cobarsi and Romas Geleziunas and Leselbaum, {Anne R.} and Cora Loste and Michael Meulbroek and Cristina Miranda and Jose Mu{\~n}oz and Jordi Naval and Aroa Nieto and Ferran Pujol and Jordi Puig and {the AELIX002 Study Group}",

year = "2022",

month = dec,

doi = "10.1038/s41591-022-02060-2",

language = "English",

volume = "28",

pages = "2611--2621",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

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Bailón, L, Llano, A, Cedeño, S, Escribà, T, Rosás-Umbert, M, Parera, M, Casadellà, M, Lopez, M, Pérez, F, Oriol-Tordera, B, Ruiz-Riol, M, Coll, J, Perez, F, Rivero, À, Leselbaum, AR, McGowan, I, Sengupta, D, Wee, EG, Hanke, T, Paredes, R, Alarcón-Soto, Y, Clotet, B, Noguera-Julian, M, Brander, C & the AELIX002 Study Group 2022, 'Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial', Nature Medicine, vol. 28, no. 12, pp. 2611-2621. https://doi.org/10.1038/s41591-022-02060-2

Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. / Bailón, Lucia; Llano, Anuska; Cedeño, Samandhy et al.
In: Nature Medicine, Vol. 28, No. 12, 12.2022, p. 2611-2621.

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

TY - JOUR

T1 - Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection

T2 - a randomized, placebo-controlled phase 1 trial

AU - Bailón, Lucia

AU - Llano, Anuska

AU - Cedeño, Samandhy

AU - Escribà, Tuixent

AU - Rosás-Umbert, Miriam

AU - Parera, Mariona

AU - Casadellà, Maria

AU - Lopez, Miriam

AU - Pérez, Francisco

AU - Oriol-Tordera, Bruna

AU - Ruiz-Riol, Marta

AU - Coll, Josep

AU - Perez, Felix

AU - Rivero, Àngel

AU - Leselbaum, Anne R.

AU - McGowan, Ian

AU - Sengupta, Devi

AU - Wee, Edmund G.

AU - Hanke, Tomáš

AU - Paredes, Roger

AU - Alarcón-Soto, Yovaninna

AU - Clotet, Bonaventura

AU - Noguera-Julian, Marc

AU - Brander, Christian

AU - Molto, Jose

AU - Mothe, Beatriz

AU - Barriocanal, Ana María

AU - Benet, Susana

AU - Cobarsi, Patricia

AU - Geleziunas, Romas

AU - Leselbaum, Anne R.

AU - Loste, Cora

AU - Meulbroek, Michael

AU - Miranda, Cristina

AU - Muñoz, Jose

AU - Naval, Jordi

AU - Nieto, Aroa

AU - Pujol, Ferran

AU - Puig, Jordi

AU - the AELIX002 Study Group

PY - 2022/12

Y1 - 2022/12

N2 - HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml−1, >10,000 copies ml−1 for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials.

AB - HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml−1, >10,000 copies ml−1 for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials.

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DO - 10.1038/s41591-022-02060-2

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SN - 1078-8956

VL - 28

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EP - 2621

JO - Nature Medicine

JF - Nature Medicine

IS - 12

ER -

Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial

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