‘A potential first step forward’: Moderna to launch human trials for new HIV vaccines

The new jabs use the same mRNA technology behind the manufacturer’s successful Covid vaccine, but scientists warn there is a long way to go in providing lasting protection against HIV

Samuel Lovett
Science Correspondent
Wednesday 18 August 2021 19:18 BST
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About 38 million people worldwide are currently living with HIV
About 38 million people worldwide are currently living with HIV (AFP via Getty Images)
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Human trials for two new HIV vaccines developed by US biotech company Moderna are set to be launched on Thursday – a moment that has been described as a “potential first step forward” in protecting people against the deadly virus.

The manufacturer was among the first to develop a Covid-19 jab last year, and it’s hoped its ground-breaking messenger RNA (mRNA) technology will once again be put to use in overcoming one of science’s most complex challenges.

Moderna is to recruit 56 healthy people aged between 18 and 50 into its phase 1 trial, which will assess the safety of the vaccines and their ability to generate a broad range of neutralising antibodies against HIV. The study is expected to run until May 2023.

It’s believed that multiple vaccines will ultimately be needed to generate the sufficient immune response required to provide protection against the virus, which is far more accomplished than Covid in evading the body’s defences.

The spike-like protein that allows HIV to gain entry to human cells is coated in a sugar residue and hidden away from sight of the body’s antibodies, making it difficult to neutralise the virus.

HIV can also linger in the body for years before developing into Aids. During this time, the virus will frequently mutate parts of its spike protein, to the point that that they become almost unrecognisable to antibodies.

The two Moderna vaccines, named mRNA-1644 and mRNA-1574, are aiming to tackle these challenges by inducing broadly neutralising antibodies (bnABs) to levels not previously reported with other jabs.

These antibodies can target multiple variants of HIV, and are capable of neutralising stable parts of the virus that don’t change as much as it mutates.

Researchers will also be assessing the cellular immune response of the volunteers, particularly their B cells, which are responsible for producing and maintaining antibodies.

The messenger RNA technology behind Moderna’s Covid vaccine was used to generate exceptionally high levels of antibodies against Sars-CoV-2 – but given the complexities of HIV, scientists do not believe it will be as straightforward in vaccinating against the virus.

“Moderna are testing a complicated concept which starts the immune response against HIV,” said Professor Robin Shattock, an immunologist at Imperial College London.

“It gets you to first base but it’s not a home run. Essentially we recognise that you need a series of vaccines to induce a response that gives you the breadth needed to neutralise HIV.

“It’s quite likely that their technology may allow them to start to look at that process, but we’re a very long way away from an effective vaccine.”

Prof Shattock described the progression to human testing as “a potential first step forward on a very long journey”, and acknowledged that it was “exciting” that Moderna’s mRNA technology was being used in a HIV vaccine.

The biotech’s Covid vaccine delivers genetic instructions to the body which code for the production of the spike protein that coats the outside of the virus.

This triggers an immune response and allows the body to create the necessary defences – antibodies, B cells, T cells, and more – which then provide protection against the real infection.

It’s hoped a similar immunological process can be generated with regards to HIV using Moderna’s vaccine platform.

“The mRNA technology may be key to solving the HIV vaccine issue, but it’s going to be a multi-year process,” Prof Shattock said.

“It’s exciting to see that it’s being brought for this very difficult challenge but there is no likelihood of a quick outcome.”

“It remains one of the biggest challenges to overcome in vaccinology. The vaccines may help us accelerate the process, but they won’t be game-changing in terms of solving the fundamental problem, which is knowing how to induce neutralising antibodies.”

Moderna’s efforts to develop an HIV vaccine are part of a wider collaboration with the International Aids Vaccine Initiative and the Bill and Melinda Gates Foundation.

About 38 million people worldwide are currently living with HIV, while 2 million new infections are acquired each year. Since its emergence in the early 1980s, 36.3 million people are believed to have died from the virus.

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