An HIV vaccine that uses a synthetic gene to trigger an immune response might offer a way to protect against the virus where others have failed.
Most vaccines work by training immune cells called B-cells to produce antibodies against a virus. Another approach is to stimulate T-cells, which kill cells infected with the virus. This is known as inducing cellular immunity.
Previous T-cell vaccines have largely failed because of HIV’s ability to rapidly mutate and escape them.
To get around this, Lucy Dorrell at the University of Oxford and her team created a synthetic gene by stitching together 14 regions of the HIV genome that don’t tend to mutate because if they do the virus struggles to survive. This means the vaccine just focuses the immune system on conserved segments, says Dorrell.
To expose the immune system to this gene, it was inserted into three delivery vessels: two disabled viruses and a free-floating circle of DNA called a plasmid. Because vaccines often need to be administered several times to trigger a strong immune response, the hope was that this three-pronged approach would increase the chance that the T-cells would respond to the synthetic gene, even if the B-cells had started to recognise and attack the delivery vessel.
Sure enough, when the three were injected sequentially into healthy people several weeks or months apart, the volunteers produced T-cells specific to many of the 14 regions of HIV – some more strongly than others. When these T-cells were added to dishes of the volunteers’ own cells that had been infected with HIV in the lab, they stopped the virus replicating.
The team is currently fine-tuning the combination of delivery vessels, but it hopes to begin a second trial in Nairobi, Kenya, in March. This will involve vaccinating people at high risk of contracting HIV to see if it lowers infection rates. All participants will be encouraged to avoid exposing themselves to the virus regardless of whether or not they have received the vaccine.
“The work represents a significant advance in the design of vaccines targeted to induce strong cellular immunity capable of eliminating HIV infected cells” says Robin Shattock of Imperial College London.
Steven Patterson, also at Imperial, agrees that the findings are encouraging but says future research should focus on increasing the magnitude of the response to more of the regions expressed by the synthetic gene. “At this stage, we just do not know whether high responses to one or two conserved [regions] will be sufficient to protect or control virus infection,” he says.
Source: New Scientist