Modelling the Interaction Between Rationally-designed Synthetic Model Viral Protein Immunogens
EAVI2020_01
An Experimental Medicine Study Modelling the Interaction Between Rationally-designed Synthetic Model Viral Protein Immunogens and the Breadth of the Induced B and T Cell Repertoires.
1 other identifier
interventional
117
1 country
1
Brief Summary
The objective of this experimental medicine study is to determine the extent to which different prime-boost combinations influence serum neutralising antibody breadth and associated B and T cells responses. The investigators hypothesise that the different prime-boost model immunogen combinations will have differential impact on: the magnitude and breadth of induced serum neutralising antibodies; and the induced B- and T-cell responses in peripheral blood. The investigators will investigate this by challenging the immune system of healthy adults with various model immunogens based on HIV-1 Env (ConM and ConS, with and without EDC stabilisation; Mos3.1, Mos3.2 and Mos3.3, and AMC011 and 763 SOSIP) in different prime-boost combinations.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2019
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2019
CompletedFirst Posted
Study publicly available on registry
January 25, 2019
CompletedStudy Start
First participant enrolled
March 19, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2022
CompletedNovember 5, 2024
November 1, 2024
3.8 years
January 22, 2019
November 1, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Neutralising antibodies to virus expressing ConM and ConS envelopes
Serum titres of neutralising antibodies to virus expressing ConM and ConS envelopes
6 Months
Neutralising antibodies to virus expressing Mosaic envelopes
Serum titres of neutralising antibodies to virus expressing Mosaic envelopes (Mos3.1, Mos3.2, Mos3.3)
12 Months
Neutralising antibodies to virus expressing AMC011 and 763 SOSIP envelopes
Serum titres of neutralising antibodies to virus expressing AMC011 and 763 SOSIP envelopes
4 months
Study Arms (13)
Group A: ConM SOSIP and Mosaic SOSIPs
ACTIVE COMPARATORConM SOSIP 100mcg Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months Mosaic SOSIPs (Mos3.1 + Mos3.2) 100mcg (2x50mcg) Intramuscular injections into the left or right arm Administered at 12 months only
Group B: EDC ConM SOSIP and Mosaic SOSIPs
ACTIVE COMPARATOREDC ConM SOSIP 100mcg Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months Mosaic SOSIPs (Mos3.1 + Mos3.2) 100mcg (2x50mcg) Intramuscular injections into the left or right arm Administered at 12 months only
Group C: ConS UFO and Mosaic SOSIPs
ACTIVE COMPARATORConS UFO 100mcg Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months Mosaic SOSIPs (Mos3.1 + Mos3.2) 100mcg (2x50mcg) Intramuscular injections into the left or right arm Administered at 12 months only
Group D: EDC ConS UFO and Mosaic SOSIPs
ACTIVE COMPARATOREDC ConS UFO 100mcg Intramuscular injections into the left or right arm Administered at 0, 3 and 6 months Mosaic SOSIPs (Mos3.1 + Mos3.2) 100mcg (2x50mcg) Intramuscular injections into the left or right arm Administered at 12 months only
Group E: ConS UFO and ConM SOSIP and Mosaic SOSIPs
ACTIVE COMPARATORConS UFO 100mcg Intramuscular injections into the left or right arm Administered at 0 and 3 months ConM SOSIP 100mcg Intramuscular injection into the left or right arm Administered at 6 months Mosaic SOSIPs (Mos3.1 + Mos3.2) 100mcg (2x50mcg) Intramuscular injections into the left or right arm Administered at 12 months only
Group F: Mosaic SOSIPs and ConM SOSIP and ConS UFO
ACTIVE COMPARATORMosaic SOSIP Mos3.1 100mcg Intramuscular injection into the left or right arm Administered at 0 months Mosaic SOSIP Mos3.2 100mcg Intramuscular injection into the left or right arm Administered at 2 months Mosaic SOSIP Mos3.3 100mcg Intramuscular injection into the left or right arm Administered at 4 months ConM SOSIP + ConS UFO 50mcg + 50mcg Intramuscular injections into the left or right arm Administered at 6 months
Group G: Mosaic SOSIPs and ConM SOSIP and ConS UFO
ACTIVE COMPARATORMosaic SOSIP Mos3.2 100mcg Intramuscular injection into the left or right arm Administered at 0 months Mosaic SOSIP Mos3.1 100mcg Intramuscular injection into the left or right arm Administered at 2 months Mosaic SOSIP Mos3.3 100mcg Intramuscular injection into the left or right arm Administered at 4 months ConM SOSIP + ConS UFO 50mcg + 50mcg Intramuscular injections into the left or right arm Administered at 6 months
Group H: Mosaic SOSIPs and ConM SOSIP and ConS UFO
ACTIVE COMPARATORMosaic SOSIP Mos3.3 100mcg Intramuscular injection into the left or right arm Administered at 0 months Mosaic SOSIP Mos3.2 100mcg Intramuscular injection into the left or right arm Administered at 2 months Mosaic SOSIP Mos3.1 100mcg Intramuscular injection into the left or right arm Administered at 4 months ConM SOSIP + ConS UFO 50mcg + 50mcg Intramuscular injections into the left or right arm Administered at 6 months
Group I: Mosaic SOSIPs and ConM SOSIP and ConS UFO
ACTIVE COMPARATORMosaic SOSIPs (Mos3.1 + Mos3.2 + Mos3.3) 100mcg (3x33mcg) Intramuscular injections into the left or right arm Administered at 0, 2 and 4 months ConM SOSIP + ConS UFO 50mcg + 50mcg Intramuscular injections into the left or right arm Administered at 6 months
Group J: 763 SOSIP
ACTIVE COMPARATOR763 SOSIP 100mcg Intramuscular injections into the left or right arm Administered at 0, 2 and 4 months
Group K: AMC011 SOSIP
ACTIVE COMPARATORAMC011 100mcg Intramuscular injections into the left or right arm Administered at 0, 2 and 4 months
Group L: 763 SOSIP and AMC011 SOSIP
ACTIVE COMPARATOR763 SOSIP and AMC011 50mcg + 50mcg Intramuscular injections into the left or right arm Administered at 0, 2 and 4 months
Group M: 763 SOSIP and AMC011 SOSIP and ConM SOSIP and Mosaic SOSIPs
ACTIVE COMPARATOR763 SOSIP and AMC011 SOSIP and ConM SOSIP and Mos3.1 and Mos3.2 SOSIPs each at 20mcg Intramuscular injections into the left or right arm Administered at 0, 2 and 4 months
Interventions
Recombinant HIV-1 trimeric gp140 Env protein: ConM SOSIP gp140. Model immunogens will be used at the dosage of 20 mcg or 50 mcg or 100 mcg and will be admixed with 500 mcg MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.
Chemically fixed version of recombinant HIV-1 trimeric gp140 Env: EDC ConM SOSIP. Model immunogens will be used at the dosage of 100 mcg and will be admixed with 500 mcg MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.
Recombinant HIV-1 trimeric gp140 Env protein: ConS UFO gp140. Model immunogens will be used at the dosage of 50 mcg or 100 mcg and will be admixed with 500 mcg MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle
Chemically fixed version of recombinant HIV-1 trimeric gp140 Env : EDC-ConS UFO. Model immunogens will be used at the dosage of 100 mcg and will be admixed with 500 mcg MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.
Mosaic gp140 Env trimers (Mos3.1, Mos3.2, Mos3.3) designed to overcome the immunodominance of hypervariable regions of Env. The immunogen will be used at the dosage of 100 mcg (100mcg or 2 x 50 mcg or 3 x 33 mcg) or at 40 mcg (2 x 20mcg) and will be admixed with 500 mcg MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.
HIV-1 envelope sequence, identified from two HIV infected individuals that displayed HIV neutralisation breadth early in infection (less than 12 months). The immunogen will be used at the dosage of 20 mcg or 50mcg or 100mcg and will be admixed with 500 mcg MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.
HIV-1 envelope sequence, identified from two HIV infected individuals that displayed HIV neutralisation breadth early in infection (less than 12 months). The immunogen will be used at the dosage of 20 mcg or 50mcg or 100mcg and will be admixed with 500 mcg MPLA formulated in liposomes and administered by intramuscular injection into the left or right deltoid muscle.
Eligibility Criteria
You may qualify if:
- Healthy male and female volunteers aged between 18 and 55 years.
- Available for ALL follow-up visits for the duration of the study.
- Entered and clearance obtained from The Over volunteering Prevention System (TOPS) database (to avoid impact of any co-administered investigational products or treatments on our outcomes).
- Women of childbearing potential willing to use a highly effective method of contraception for the duration of the study until a minimum of 12 weeks after the final injection. Periodic abstinence (calendar, symptothermal and post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Willing and able to give written informed consent.
You may not qualify if:
- History of any medical, psychological or other condition, clinically significant laboratory result at screening, or use of any medications which, in the opinion of the investigators, would interfere with the study objectives or volunteers safety.
- Any history of angioedema.
- History of urticaria deemed significant by the Chief Investigator.
- HIV-1 or HIV-2 antibody positive or indeterminate upon screening, or history of receipt of Env-based HIV immunogens (which would render the volunteers non-naive to the model immunogens).
- Unable to read and/or speak English to a fluency level adequate for the full comprehension of study procedures and consent.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
NIHR Imperial Clinical Resarch Facility
London, W12 0HS, United Kingdom
Related Publications (1)
Pollock KM, Cheeseman HM, McFarlane LR, Day S, Tolazzi M, Turner HL, Joypooranachandran J, Shramko K, Dispinseri S, Mundsperger P, Bontjer I, Lemm NM, Coelho S, Tanaka M, Cole T, Korber B, Katinger D, Sattentau QJ, Ward AB, Scarlatti G, Sanders RW, Shattock RJ. Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth. EBioMedicine. 2025 Feb;112:105544. doi: 10.1016/j.ebiom.2024.105544. Epub 2025 Jan 2.
PMID: 39753033DERIVED
Study Officials
- PRINCIPAL INVESTIGATOR
Katrina Pollock
Imperial College London
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Masking Details
- Volunteers will be blinded to their treatment regimes, and laboratory teams undertaking immunological analysis will be blinded to group and dosing regimen to prevent in-house analysis bias. The clinical team will remain un-blinded throughout.
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2019
First Posted
January 25, 2019
Study Start
March 19, 2019
Primary Completion
December 31, 2022
Study Completion
December 31, 2022
Last Updated
November 5, 2024
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- CSR
- Time Frame
- 12 months from when the experimental study officially closes
- Access Criteria
- Directly from Professor Robin Shattock (r.shattock@imperial.ac.uk)
Results from this study will be disseminated locally and to the wider scientific community at conferences and in published open-access peer-reviewed journals, as appropriate. Any data used for publication will be fully anonymised. The investigators plan to publish the data and hold onto the data for 10 years.