Glenda Gray, head of the South African Medical Research Council
, presented the results from a small study, HVTN097, which gave a version of the RV144 vaccine protocol to 100 volunteers (51 men and 49 women).
The vaccine actually contains two components. One is a vaccine called ALVAC. This is a vector vaccine, consisting of HIV proteins encased in the shell of another virus. This ‘fake infection’ is intended to stimulate the cellular immune response (the part of the immune system that stimulates CD8 cells to attack other, infected cells). It was given in four components: zero, one, three and six months from the start of the study. The other component is called AIDSVAX. This consists of HIV envelope (sruface) proteins intended to stimulate the humoral immune response – the part of the immune system that generates the soluble proteins called antibodies that directly attack viruses. It was given at month three and month six.
Why has it taken so long to re-try a vaccine that produced positive results five years ago? The main problem is that expectations of the original study were so low that Vaxgen, the company making AIDSVAX, used all its stock and did not make more so the vaccine has had to be re-manufactured from scratch.
As was observed in the original study, the South African vaccine did not stimulate the cellular immune response to a useful degree. Some degree of immune response to HIV was stimulated in volunteers’ CD4 cells, and was more common and stronger in the South African trial: 69% of South African volunteers’ CD4 cells became sensitive to HIV as opposed to 50% of original vaccine recipients’ cells. However, there was little evidence of the desired CD8 response – only 5% of South African and 0.6% of the original Thai recipients had CD8 responses.
In contrast, and as seen in the original study, there was a strong and universal antibody response generated to the gp120 component of HIV. This protein forms the ‘knobs’ on the surface of HIV that attach to cells and is one of the components of AIDSVAX. There was also a near-universal (98.6%) response to a specific part of gp120 called the V1-V2 loop, a section of the protein chain that first attaches to cells. More analysis of the immune responses is underway and it looks as if the antibodies generated in the vaccine recipients in South Africa have a stronger effect against lab-engineered HIV viruses, being able, for instance, to neutralise (disable from reproducing) 25% more clade B viruses than Thai-recipient antibodies.
In January 2015 a new study, HVTN100, will give trial volunteers a vaccine based on RV144 but reformulated to contain proteins from the HIV subtype (clade) most common in south Africa, namely clade C instead of the Thai clade A/E. Depending on efficacy, this could then lead to a much bigger efficacy trial.