A Phase I/IIa Randomized, Placebo-Controlled Trial of Conserved-Mosaic T-cell Vaccine in a Regimen With Vesatolimod and Broadly Neutralizing Antibodies in Adults Initiated on Suppressive Antiretroviral Therapy During Acute HIV-1

The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) compared to placebo, to induce HIV-1 control during analytic treatment interruption (ATI).

开始日期2024-04-01

申办/合作机构

National Institute of Allergy & Infectious Diseases

[+2]

NCT04586673

/ Completed临床1期IIT

A Phase I Dose Escalation Open Label Trial to Assess Safety and Immunogenicity of Candidate ChAdOx1- and MVA- Vectored Conserved Mosaic HIV-1 Vaccines Given Sequentially to Healthy HIV-1 Negative Adult Volunteers in Oxford, UK

The object of the study is to assess the safety profile of candidate vaccines ChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVcnsv4 administered sequentially in healthy HIV-1/2 negative adult volunteers.
In addition, the study will assess the immune responses generated of the candidate vaccines ChAdOx1.tHIVconsv1, MV.tHIVconsv3 and MVA.tHIVconsv4 administered sequentially in healthy HIV-1/2 negative adult volunteers.
3 healthy, HIV-1 negative adult volunteers will receive one vaccination of low dose ChAdOx1.tHIVconsv1. A further 10 healthy, HIV-1 negative adult volunteers will receive a higher dose of ChAdOx1.tHIVconsv1, followed by one vaccination each of MVA.tHIVconsv3 and MVA.tHIVconsv4 4 weeks later.

开始日期2021-07-03

申办/合作机构

University of Oxford

NCT03844386

/ Completed临床1期IIT

A Phase I Pilot Study to Evaluate the Safety and Immunogenicity of the HIV-1 Vaccines MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) Given Alone or In Combination in HIV-1-Infected Adults Suppressed on Antiretroviral Therapy - The M&M Study

This is a double blind, randomized, placebo-controlled, parallel design, study in which 24 HIV-infected participants with durable viral suppression will be randomly assigned to receive vaccination with MVA.tHIVconsv3 (M3), MVA.tHIVconsv4 (M4), M3+M4 combined, or placebo. Participants will be randomized 7:7:7:3 to one of four study arms, and receive study treatment or placebo at Day 0. Each enrolled participant will complete the study in approximately 33.5 weeks (8.4 months).
The purpose of this study is to find out:
If it is safe for people to receive injections of two investigational HIV vaccines, called MVAtHIVconsv3 and MVAtHIVconsv4 alone or in combination.
If giving participants these vaccine doses will increase their immune system's ability to kill HIV virus.

开始日期2019-04-22

申办/合作机构

The University of North Carolina at Chapel Hill

[+1]

100 项与 MVA.tHIVconsv3 相关的临床结果

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100 项与 MVA.tHIVconsv3 相关的转化医学

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100 项与 MVA.tHIVconsv3 相关的专利（医药）

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项与 MVA.tHIVconsv3 相关的文献（医药）

2025-03-01·The Lancet Microbe

Safety and immunogenicity of the ChAdOx1–MVA-vectored conserved mosaic HIVconsvX candidate T-cell vaccines in HIV-CORE 005.2, an open-label, dose-escalation, first-in-human, phase 1 trial in adults living without HIV-1 in the UK

Article

作者: Cicconi, Paola ; Baines, Andrea ; Fernandez, Natalia ; Glaze, Molly ; Baker, Megan ; Conway, Oliver ; Quaddy, Jack ; Watson, Marion ; Crook, Alison ; Hayes, Peter J ; Poulton, Ian ; Byard, Nicholas ; Thomas, Merin ; Jenkin, Daniel ; Wee, Edmund G-T ; Platt, Abigail ; Akis Yildirim, Belkis M ; Larkworthy, Colin ; Hanke, Tomáš ; Luciw, Michael ; Borthwick, Nicola

BACKGROUNDAn HIV-1 vaccine is long overdue. Although vaccine research focuses on the induction of broadly neutralising antibodies, challenging infections such as HIV-1 could require parallel induction of protective T cells. It is important to recognise that not all T cells contribute to protection equally. Previously, we developed a T-cell immunogen-based bivalent mosaic vaccine, HIVconsvX, delivered by vaccine vectors ChAdOx1 and modified vaccinia Ankara. In this study, we tested the HIVconsvX vaccine regimen for the first time in humans. Other ongoing trials will assess the contribution of the vaccine-induced killer T cells to the control of HIV-1.METHODSHIV-CORE 005.2 was an open-label, dose-escalation, first-in-human, phase 1 trial done at the Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK. Eligible participants were healthy volunteers aged 18-65 years living without HIV-1 and at a low likelihood of acquiring it. Because it was the first administration of ChAdOx1.tHIVconsv1 (C1) to humans, participants were assigned stepwise to two groups. Volunteer group 1 received a low dose of C1 on enrolment. Following a satisfactory safety review 7 days after vaccination, volunteer group 2 received a full dose of C1 boosted by vaccines MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) 4 weeks later in regimen C1-M3M4 and were followed up until day 140. Focusing on the full vaccine doses in group 2, the primary outcome was the local and systemic safety of the vaccine. The secondary outcome was the frequency and breadth of epitope recognition by vaccine-induced T cells determined by IFN-γ ELISPOT assay using peripheral blood mononuclear cells (PBMC) at peak (1 and 2 weeks after the M3M4 boost) and at the end of the study, assessed against volunteer's pre-vaccination levels. The HIV-CORE 005.2 trial is registered at ClinicalTrials.gov (NCT04586673) and is closed.FINDINGSBetween July 3, 2021, and Aug 3, 2022, 13 participants were recruited and assigned to group 1 (n=3) and group 2 (n=10). Low-dose C1 was safe and well tolerated in group 1, and all three vaccine components were well tolerated in volunteer group 2. There were no serious adverse events. Local and systemic reactogenicities were consistent with intramuscular needle administration of immunogenic substances. All volunteers responded, and their vaccine-elicited T-cell frequencies peaked at a median of 4433 (IQR 2750-5820) IFN-γ spot-forming units per 10⁶ PBMC and recognised a median of 9 (IQR 9-10) peptide pools out of 10, indicating that the responses were broadly specific and each vaccine recipient targeted at least nine epitopes on HIV-1. These frequencies were 7·4 times lower by day 140 (ie, 3 months later). T cells proliferated upon antigen re-exposure and displayed multiple effector functions, recognised variant epitopes, and inhibited HIV-1 from the four major global clades A, B, C, and D.INTERPRETATIONThese results inform and support a programme of clinical evaluations of the HIVconsvX T-cell vaccines together with other cutting-edge tools for HIV-1 cure and prevention such as latency reactivating agents, passively infused combinations of broadly neutralising antibodies, and active Env-based vaccines or immunomodulators.FUNDINGEU Horizon 2020 Research and Innovation programme, Medical Research Council and Foreign Commonwealth and Development Office Concordat agreement, European and Developing Countries Clinical Trials Partnership, National Institute for Health Research Oxford Biomedical Research Centre, and IAVI.

2013-11-01·Vaccine3区 · 医学

Absence of systemic toxicity changes following intramuscular administration of novel pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines to BALB/c mice

3区 · 医学

Article

作者: Caroline Brennan ; Beatrice Ondondo ; Tomáš Hanke ; Alfredo Nicosia ; Steven J. Crome

BACKGROUNDThe systemic toxicity of three candidate HIV-1 vaccines plasmid pSG2.HIVconsv DNA (D), ChAdV63.HIVconsv (C) and MVA.HIVconsv (M) expressing chimeric immunogen derived from the most conserved regions of the HIV-1 proteome was evaluated in two repeat-dose studies in the male and female BALB/c mice.METHODSIn study UNO011, mice received three doses of 2×10(7) plaque-forming units of MVA.HIVconsv vaccine (MMM). In study UNO012, mice received 3 doses of 50μg of pSG2.HIVconsv DNA followed by a single dose of 5.95×10(9) virus particles of ChAdV63.HIVconsv vaccine (DDDC). Similarly constituted control groups received the vehicle alone (phosphate buffered saline) at the same volume-dose. All vaccines were administered by intramuscular needle injection into the right hind limb at 14-day intervals and animals were sacrificed 7 days after the last dose. Assessment of local and systemic toxicity was made. Induction of HIV-1-specific responses was confirmed. Parameters assessed included clinical condition, body weight, food consumption, ophthalmoscopy, haematology, blood chemistry, organ weight and macroscopic and microscopic pathology.RESULTSIn both studies, treatment with the candidate vaccines elicited strong HIV-1-specific T-cell responses. The vaccine treatment was well-tolerated without any adverse systemic toxicological changes. The local toxicity findings observed in these studies were consistent with the predicted response to a vaccine/substance administration by intramuscular injection.CONCLUSIONSThe three novel anti-HIV-1 vaccines were well tolerated when administered by intramuscular injection to BALB/c mice. These results supported an application for authorisation by the Medicines and Healthcare Products Regulatory Agency of the UK to test these vaccines for the first time in phase I clinical trials in healthy both uninfected subjects and HIV-1-infected patients stable on antiretroviral treatment.

2012-01-28·AIDS2区 · 医学

Prime-boost regimens with adjuvanted synthetic long peptides elicit T cells and antibodies to conserved regions of HIV-1 in macaques

2区 · 医学

Article

作者: David Montefiori ; Tomáš Hanke ; Alice Mbewe-Mvula ; Jan W. Drijfhout ; Esther D. Quakkelaar ; Guillaume B. Stewart-Jones ; Anne Bridgeman ; Stefano Colloca ; Andrew J. McMichael ; Nicola Borthwick ; Alfredo Nicosia ; Cornelis J.M. Melief ; Maximillian Rosario

OBJECTIVESAdministration of synthetic long peptides (SLPs) derived from human papillomavirus to cervical cancer patients resulted in clinical benefit correlated with expansions of tumour-specific T cells. Because vaginal mucosa is an important port of entry for HIV-1, we have explored SLP for HIV-1 vaccination. Using immunogen HIVconsv derived from the conserved regions of HIV-1, we previously showed in rhesus macaques that SLP.HIVconsv delivered as a boost increased the breath of T-cell specificities elicited by single-gene vaccines. Here, we compared and characterized the use of electroporated pSG2.HIVconsv DNA (D) and imiquimod/montanide-adjuvanted SLP.HIVconsv (S) as priming vaccines for boosting with attenuated chimpanzee adenovirus ChAdV63.HIVconsv (C) and modified vaccinia virus Ankara MVA.HIVconsv (M).DESIGNPrime-boost regimens of DDDCMS, DSSCMS and SSSCMS in rhesus macaques.METHODSAnimals' blood was analysed regularly throughout the vaccination for HIV-1-specific T-cell and antibody responses.RESULTSWe found that electroporation spares DNA dose, both SLP.HIVconsv and pSG2.HIVconsv DNA primed weakly HIVconsv-specific T cells, regimen DDDCM induced the highest frequencies of oligofunctional, proliferating CD4(+) and CD8(+) T cells, and a subsequent SLP.HIVconsv boost expanded primarily CD4(+) cells. DSS was the most efficient regimen inducing antibodies binding to regions of trimeric HIV-1 Env, which are highly conserved among the four major global clades, although no unequivocal neutralizing activity was detected.CONCLUSIONThe present results encourage evaluation of the SLP.HIVconsv vaccine modality in human volunteers along the currently trialled pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines. These results are discussed in the context of the RV144 trial outcome.

100 项与 MVA.tHIVconsv3 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床2期	美国	National Institute of Allergy & Infectious Diseases	2024-04-01
HIV感染	临床2期	巴西	National Institute of Allergy & Infectious Diseases	2024-04-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04586673 (CTgov)	临床1期	HIV感染	13	ChAdOx1.tHIVconsv1 (C1) (ChAdOx1.tHIVconsv1 Low Dose)	糧艱齋夢夢製構鹽廠獵(壓壓艱夢鑰觸鑰鏇簾獵) = 顧壓獵醖網網淵鑰網繭鑰構鹽襯鏇鏇繭鏇鹽選 (積製壓鹹壓膚獵淵糧顧, 餘範憲齋艱選壓憲範鹽 ~ 顧糧廠齋鏇製鏇夢壓積) 更多	-	2024-09-03
				MVA.tHIVconsv4 (M4)+MVA.tHIVconsv3 (M3)+ChAdOx1.tHIVconsv1 (C1) (ChADOx1.tHIVconsv1 Higher Dose)	糧艱齋夢夢製構鹽廠獵(壓壓艱夢鑰觸鑰鏇簾獵) = 築淵艱糧艱顧簾製範觸鑰構鹽襯鏇鏇繭鏇鹽選 (積製壓鹹壓膚獵淵糧顧, 淵願襯鏇鬱願蓋鹽憲構 ~ 廠鏇鏇範範獵鹹糧糧鬱) 更多
NCT03844386 (M&M, CTgov)	临床1期	HIV感染	26	MVA.tHIVconsv3 (MVA.tHIVconsv3 (M3))	齋簾製鹽餘壓襯鏇淵獵(遞餘淵餘選簾窪選窪積) = 夢製鑰齋鏇築艱選餘顧夢壓艱積窪齋憲蓋鹽齋 (製衊願蓋鹽鬱鏇廠壓鹽, 糧蓋鑰餘鬱遞鹽衊構襯 ~ 淵餘顧鹹顧衊窪範獵蓋) 更多	-	2022-08-09
				MVA.tHIVconsv4 (MVA.tHIVconsv4 (M4))	齋簾製鹽餘壓襯鏇淵獵(遞餘淵餘選簾窪選窪積) = 觸鹽範鬱窪選蓋醖選憲夢壓艱積窪齋憲蓋鹽齋 (製衊願蓋鹽鬱鏇廠壓鹽, 醖鬱淵艱醖鬱襯憲膚簾 ~ 鑰鹹網膚繭鏇窪簾襯範) 更多