Investigating Immunisation Strategies of DNA, MVA and CN54rgp140 Adjuvanted With GLA-AF to Maximise Antibody Responses — UKHVCSpoke003  

HIV Clinical Trial

Official title: A Phase I Clinical Trial Investigating Immunisation Strategies Using DNA, MVA and CN54rgp140 Adjuvanted With GLA-AF to Maximise Antibody Responses

Status Completed

Clinical Trial Summary

UKHVC Spoke 003 is a randomised Phase I, two centre study which will explore the impact of shortening a vaccination regimen using deoxyribonucleic acid (DNA) (CN54ENV and ZM96GPN), Modified Vaccinia Ankara - C (MVA-C) and CN54rgp140 adjuvanted with glucopyranosyl lipid A adjuvant - aqueous form (GLA-AF). The study population will be 40 healthy male and female volunteers 18 to 45 years old who are at low risk of HIV infection are to be recruited.

Study participants will be immunised with trial immunogens:

• 8mg DNA: one plasmid encoding a gag-pol-nef polypeptide derived from the 96ZM651-8 clone and one plasmid encoding gp140 env derived from clade C 97CN54

• 1.108 TCID50 MVA-C (nominal titre) expressing the gag-pol-nef and gp120 env proteins derived from clade-C 97CN54

• 100ug CN54rgp140, a trimeric recombinant envelope protein derived from clade C 97CN54

• 5ug GLA-AF, an aqueous glucopyranosyl lipid A adjuvant

All immunisations will be administered by the intramuscular route (IM). CN54gp140 and GLA will be mixed together before administration, and immunogens will be delivered in combination regimens

Clinical Trial Description

This is a phase I study exploring the safety and potency of five HIV vaccines in healthy volunteers. The main aim is to see whether three of the five vaccines can be given together rather than one after the other, in five rather than seven sets of vaccinations and a course shortened by eight weeks. All volunteers will receive three injections of the first two vaccines (DNA plasmids) and half will be randomly assigned to receive two injections each of the second (MVA-C) and subsequent vaccines (CN54rgp140 mixed with GLA-AF) during the same visit or two injections of the MVA-C followed by two of CN54rgp140 mixed with GLA-AF.

The investigators are interested in ensuring that the vaccines are safe and also that the immune responses in the two groups of volunteers are similar. The three vaccines have all been shown to stimulate the immune response to specific parts of the HIV virus and none are infectious. The first vaccine consists of two DNA plasmids. When injected into muscle cells small parts of the HIV virus which are encoded by the DNA are produced and these are then recognised by the immune system. The second vaccine MVAC, is derived from vaccinia virus which has been modified so that it cannot divide. The virus (Modified Vaccinia Ankara (MVA)) actually expresses the same portions of HIV as the DNA and results in amplification of the responses seen. The third vaccine is a synthetically produced component of the HIV viral outer coat and it will be administered with an additive which has been shown to greatly enhance particular types of immune response which have recently been shown to play a role in protection against infection ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV

• NCT number: NCT01922284
• Study type: Interventional
• Source: Imperial College London
• Status: Completed
• Phase: Phase 1
• Start date: June 2013
• Completion date: December 2015