Commentary: After 40 years of AIDS, why do we still not have an HIV vaccine?


Historically, the best way to eradicate a disease is to have an effective vaccine. Yet despite almost 40 years of intensive research and multiple clinical trials, an HIV vaccine remains elusive. 

This is not for a lack of funding – it is estimated that US$17 billion was invested globally in vaccine research and trials from 2000 to 2021 alone, coming largely from governments, and to a lesser extent from pharmaceutical companies and philanthropies.

HIV is one of the fastest-mutating viruses ever studied, with various strains and subtypes that make a globally effective vaccine difficult to develop.

Another hurdle is the absence of appropriate animal models to test the vaccines on. Finally, there is still limited information regarding what constitutes natural immune responses that protect against HIV infection and that can be emulated in vaccine design.

This decade alone, four vaccine trials have been stopped because of lack of efficacy. The only study that showed modest result was RV144, which was conducted on more than 16,000 participants in Thailand between 2003 and 2006. The study showed that the vaccine efficacy against acquisition of infection was 31.2 per cent.  

The treatment would have needed a 50 per cent protection rate for regulatory approval.

Nevertheless, whilst these vaccine trials may have proved futile, they have yielded valuable insight needed to improve vaccine design and vaccination schedules.

The HIV-1 vaccine field is now at a crossroads. There are at present no active clinical trials for HIV vaccines. However, research in vaccine development is still ongoing in the laboratory and with animal studies. It is now focused on the development of techniques to induce broadly neutralising antibodies. Several strategies are currently being pursued, including B-cell lineage vaccines, germline-targeting vaccines, and epitope-targeted vaccines.

An HIV vaccine, even one of moderate efficacy, would be very cost-effective and have a lasting and substantial public health impact as part of a comprehensive prevention response.

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