HIV vaccine: scientific advances spark cautious optimism

Gary Finnegan

Gary Finnegan

December 1st, 2023

Gary Finnegan

‘In a field beset by false dawns, some researchers dare to believe a HIV vaccine could be on the horizon ‒ but any breakthrough is still many years away’

An estimated 39 million people worldwide are living with HIV. Outcomes for infected individuals have improved significantly since the 1980s’ AIDS epidemic, and the risk of spreading the disease has fallen ‒ thanks to a combination of antiretroviral medicines and PrEP (pre-exposure prophylaxis). For HIV positive individuals, medicines can reduce the level of the virus in the body to the point where it is undetectable and untransmittable. 

Key points

  • 30 years of research has yet to deliver a HIV vaccine 
  • HIV vaccine research helped accelerate COVID-19 vaccine development 
  • Success of COVID-19 vaccines could informs HIV vaccine development
  • More than 20 vaccine candidates are in the pipeline

However, despite this progress, the search for a HIV vaccine continues. ‘The world needs a HIV vaccine,’ says the IAVI, a non profit scientific research body based in the US. ‘Only a vaccine will end AIDS.’ 

The organisation, one of several that has invested heavily in vaccine development, says the tantalising appeal of a breakthrough HIV vaccine is that it could provide long-lasting protection for a wide range of people. A preventative vaccine would have the potential to eliminate the stigma associated with HIV and the burden of taking medication for life.

HIV vaccination: if it were easy, we would already have a vaccine

While HIV attracts far less attention today than it did in past decades when HIV/AIDS first burst into the public consciousness, several research and funding agencies continue to support the quest for a HIV vaccine that could end the condition as a global public health concern. 

‘The hard truth is the science of HIV vaccine development is extremely challenging,’ said Mitchell Warren, Executive Director of AVAC, a non-profit dedicated to HIV prevention. ‘But this is not the time to dial back support for ongoing research. Far from it – HIV remains a global threat, and a safe, efficacious and accessible HIV vaccine is still needed to provide a durable end to the pandemic.’ 

The technical barriers to developing a successful HIV vaccine include a lack of natural immunity to HIV, variability of HIV types, lack of ‘correlates of protection’ for HIV (measurable signs that a person is immune), and lack of animal models that can reliably predict vaccine efficacy in humans. However, the field has been inching forward, learning from failures and near misses. 

‘The multiple studies done to date, including those in which the vaccine candidates failed to protect, have led us to know what doesn’t work related to this virus and the immune system, and it has also identified a number of insights that are critical building blocks to know what might actually protect from infection,’ says Warren.

There is a degree of cautious optimism in some quarters that a breakthrough could be on the horizon, perhaps even over the course of the next decade. HIV vaccines based on the mRNA vaccine technology that was used to develop COVID-19 vaccines are being tested by several research consortia. 

In fact, past investment in HIV research have helped to put the search for a COVID-19 vaccine on the front foot. Now, experience with COVID vaccines could be a catalyst for HIV vaccination. ‘There is no doubt that HIV vaccine research gave COVID-19 vaccine R&D a running start,’ says Warren. ‘The recent award of the Nobel Prize to Katalin Karikó and Drew Weissman for their work on using mRNA as a vector, or delivery platform, for vaccines, actually began decades ago in their work to develop an HIV vaccine.’

There are currently three Phase I studies looking using the same mRNA platform to elicit the neutralising antibodies that have been seen in recent studies to confer partial protection from HIV. ‘This is really exciting science, combining the proven platform with the antibody responses that were seen in other studies,’ Warren says. ‘Will it work? We don’t know, and that is why the studies are so important right now.’

He acknowledged that a vaccine for COVID-19 was relatively ‘easy compared to HIV’: ‘At every turn [HIV] has proven to be an even harder virus to make a vaccine for than we ever imagined.’ A few other approaches are showing promise, he adds, but we’re still years away from a licensed HIV vaccine.

Seasoned HIV researchers and advocates have been down this road before. Over the years, several vaccine candidates have come and gone, without a major breakthrough. In 2009, HIV vaccine trials were hailed as ’very encouraging’ but ultimately failed to translate into an effective vaccine. As recently as this year, a large trial of a candidate vaccine delivered disappointing results

‘Encouraging’ science, but challenges remain 

In addition to the mRNA platform, there is another important approach under investigation that uses cytomegalovirus, or CMV, a very common virus, as a vector. This has worked well in animal studies and, in October, the US National Institutes of Health (NIH) funded the first human Phase 1 study. There are issues around how to ensure this is a safe platform in humans, but it shows the variety of approaches scientists are taking. 

There is also the germ-line targeting approach that relies on ‘sequential immunisation’. ‘HIV is constantly changing, which is a challenge for antibodies,’ Warren says. ‘So now there’s a Phase I study exploring sequential immunisation, which is vaccinating people with a sequence of slightly tweaked versions of the vaccine to try to get a step or two ahead of the virus.’

Warren says that while these promising approaches are now in early phase clinical trials, it remains difficult to forecast how or when a breakthrough might come. If these initial studies go well, larger trials in humans could begin in three years, with results coming through a couple of years after that. ‘There is lots of energy in the field right now to explore some approaches based on recent insights and results,’ he says. ‘Beyond that, it is impossible to predict.’ 

In the meantime, vaccine researchers continue the search for a HIV vaccine that could bring an end to a pandemic that gripped the public imagination in the 1980s and continues to be a burden on individuals and health systems. 

Further reading:

Could PrEP be viewed as a HIV ‘vaccine’?

In addition to vaccines ‒ which train the immune system to fight off viruses ‒ some researchers are also focused on long-acting forms of PrEP. Instead of regularly taking medication, the idea is to have an injection that would be effective for about 12 months. 

A version of PrEP that lasts a couple of months is already approved in some countries. ‘It’s not an AIDS vaccine, but it may be the closest thing to one so far,’ says Science, a publication of the American Association for the Advancement of Science (AAAS).

There are currently three types of PrEP: an oral pill, an injectable medication, and a ring inserted into the vagina. Each of these PrEP options requires people either to have repeated injections or a monthly ring. Oral PrEP has been around for a decade and, although it has been effective, it is not yet used by (or available to) all who would benefit from it. 

‘They are not a vaccine – which is why we still need to develop one,’ says Mithcell. ‘But, these PrEP options exist today and a vaccine doesn’t yet, so we really need to focus on delivering the options we have today at scale and with equity, while simultaneously developing the additional options we still need for a sustainable end to this pandemic.’