Researchers aim to develop a functional cure for HIV using therapeutic vaccines
EU-funded researchers are leading efforts to develop a functional cure for HIV using innovative therapeutic vaccines to halt the progression of the devastating virus, increase the availability and affordability of treatment, and improve patients' quality of life.
The approach, which has undergone promising proof-of-concept preclinical and clinical trials in the EU-funded IHIVARNA project and is being investigated further in the HIVACAR initiative – also funded by the EU – marks a significant advance in preventive and therapeutic efforts to tackle the HIV epidemic worldwide.
‘The aim is to achieve a functional cure for HIV. No therapeutic vaccine or drug combination has achieved this goal. Therefore expectations are very high,’ says Felipe García, the coordinator of both projects at Spanish research institute IDIBAPS.
A functional cure would mean the immunodeficiency virus goes into remission, infected cells cease to replicate and the patient’s viral load is maintained at undetectable levels, preventing the onset of AIDS and other co-occurring diseases.
Although it would not eradicate HIV infection, an effective therapeutic vaccine would enable patients to live an almost normal life, less reliant on taking a daily cocktail of antiretroviral drugs in order to keep the disease under control. And while prevention measures would still be necessary, the risk of transmission to other people would be minimised, helping to halt the spread of HIV.
Vaccines on trial
In the IHIVARNA project, the researchers made important progress toward achieving that goal, using rational design techniques to develop immunogens – proteins encoded with mRNA messenger molecules capable of eliciting an immune response to HIV-1, the most widespread form of the virus.
Successful preclinical and toxicological tests enabled the team to obtain regulatory approval for a proof-of-concept candidate vaccine, leading to phase I and phase II clinical trials, including a first-in-human dose-escalating trial with HIV-infected individuals.
‘Overall, the vaccine was safe and well tolerated. It was able to induce moderate HIV-specific immune responses in the phase I clinical trial. Additional results from the phase II clinical trial are being analysed,’ García says.
In the follow-up project HIVACAR, the researchers are planning to administer therapeutic vaccines customised for each patient, alongside a potent antibody able to neutralise the binding of the virus to infected cells and a latency reversing agent, a molecule capable of unmasking the virus.
‘Using a computer-simulation-assisted drug-development technique, we have sequenced HIV-1 from four patients and have prepared four personalised vaccines that will initially be tested in animal models. Clinical trials will subsequently be conducted with a number of HIV patients in five hospitals in four European countries,’ García says. ‘The final objective is to be able to offer an alternative to current combined antiretroviral therapy for HIV-1 infected patients, although as these are proof-of-concept trials more research and further studies will be needed to confirm the results.’
Urgently seeking new strategies
A therapeutic vaccine capable of achieving a functional cure would have an enormous impact on the lives of HIV patients, who are currently reliant on taking regular doses of antiretroviral drugs for life in order to suppress the disease, often with significant side effects.
Although combined life-long antiretroviral therapy (cART) has proven highly effective in preventing disease progression and death, it has a number of public health, economic and clinical limitations. Standard cART does not fully restore health or a normal immune status in HIV-infected individuals, and patients still experience co-morbidities such as cardiovascular disease, bone disorders and cognitive impairment.
Moreover, access to treatment and the cost of the drugs is an impediment in many areas of the world, especially in developing countries which are home to a majority of the 37 million HIV patients globally. Despite improved awareness, prevention measures and more effective treatments, 2 million people still become infected with HIV worldwide each year.
‘These factors underscore the urgent need for new preventive and therapeutic strategies to be developed and tested,’ García says.
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