The St Stephen’s AIDS Trust of the Chelsea and Westminster hospital in London has teamed up with the International AIDS Vaccine Initiative (IAVI), to test IAVI's latest HIV vaccine candidate.
The Trust is looking for 32 healthy HIV-negative men and women at low risk of HIV infection to participate in the trial.
At the same time another trial, using the same vaccine but a different schedule of dosing and a vaccine modified to act against the most common type of HIV there, will take place in India.
The vaccine aims to stimulate the CD8 cells that kill off HIV-infected cells. This means that a successful vaccine would not completely prevent HIV infection but would enable the immune system to contain HIV, reducing viral replication and viral load and hopefully delaying or preventing the development of AIDS.
This is the same mode of action as the candidate in the ill-fated STEP Trial, which was ended last year when it was found that the vaccine was at best ineffective and at worst may have made people more vulnerable to HIV infection.
However the trials of the new vaccine, dubbed TBC-M4, differ from the STEP trial in two ways.
Firstly, the vaccine uses a different inactivated virus as its ‘vector’. The segments of HIV genes that (it is hoped) will stimulate an immune response are contained in the shell of another virus which acts as a way of establishing a ‘fake infection’. The shell of the other virus is called the vector
HIV vaccines of this type have to use another virus as their vector because when inactivated whole versions of HIV itself were used in animal trials, they eventually reverted to a disease-causing type, leading to a delayed form of AIDS.
The viral vector in this trial is MVA (Modified Vaccinia Virus), an inactivated relative of the smallpox virus. This has the advantage that trial volunteers’ should not have any pre-existing immunity to the vector. The Merck Ad5 vaccine used in the STEP Trial used a common-cold virus as a vector, and the pre-existing immunity many volunteers had to this virus may have been a factor in its lack of efficacy and possible harmfulness.
Secondly, the new trial uses a so-called prime-boost method. In this type of vaccine, selected HIV genes are first injected as ‘naked’ DNA without any viral vector. The idea is that this should prime the body to mount a stronger immune response to the vector vaccine when it is injected later. The DNA gene-package used is called ADVAX and has the advantage of being relatively cheap to manufacture. There is no danger that the `naked` DNA will recombine to form a disease-causing virus.
The TBC-M4 vaccine has already completed one trial in Chennai, India. Here the un-primed vaccine produced an immune response described as ‘modest’ by investigators. However it did produce an immune response in a higher proportion of patients than ever seen previously - 82 per cent of the 16 volunteers who received a low dose and 100 per cent of the 16 who received a high dose. It is hoped that the prime-boost design will strengthen this immune response.
That immune response will also be measured in a different way. Part of the problem with previous vaccine trials is that while tests indicated that in many cases they produced a significant immune response, in terms of activating cells, we have no idea what specific type of immune response actually suppresses HIV replication and viral load. The new vaccine trial, as well as standard immunology assays, will use an assay that measures actual antiviral activity.
Dr Jill Gilmour, IAVI’s Senior Director of Clinical Research, said: “Laboratory assays currently used in HIV vaccine clinical trials [may not be] an accurate predictor of whether a vaccine can prevent or control HIV infection. This assay will enable researchers to select the most promising vaccine candidates for large-scale efficacy testing.”
The trial is a small phase I trial that is intended to guide scientists towards ways of improving HIV vaccine candidates; it is not designed to demonstrate clinical efficacy against HIV.
Principal investigator Professor Brian Gazzard of the St Stephen’s AIDS Trust said: “We hope this trial will contribute to a better understanding of how to induce with a vaccine an immune response to protect against HIV infection and AIDS.”