Generating effective protection against HIV may require a complex vaccine consisting of a series of different viral proteins. Now, two trials of the potential components delivered via mRNA have produced promising results. The hope is mRNA technology will make it possible to deliver the vaccine as a single injection, rather than it requiring multiple ones.

Vaccines normally contain the outer protein of viruses, stimulating an immune response against the protein. Developing an HIV vaccine is especially challenging because in that virus, the protein that protrudes from the outer membrane is heavily coated with sugars, making it difficult for our immune system to produce antibodies against it. It also displays quite a lot of variety between strains – meaning even if a person’s immune system manages to produce effective antibodies, they are usually specific to only one version of the virus.

But a few individuals produce broadly-neutralising antibodies that work against many strains. Animal studies suggest vaccines that consist of a sequence of different forms of HIV proteins can reliably induce this broadly protective response, says at the Scripps Research Institute in California.

The first part of the vaccine is a modified viral protein designed to stimulate the body to produce . Later, boosters stimulate these cells to produce antibodies targeted against the outer protein.

For this approach, it makes sense to use mRNA vaccine technology, because mRNAs can be made relatively quickly and easily, says Schief. “It’s a massive advantage.”

A single mRNA vaccine can code for several different viral proteins at once, and it may even be possible to have these produced in the body at different times, he says. This means an mRNA HIV vaccine could potentially be delivered as a single dose, even though it effectively consists of a primer followed by several boosters that would usually be delivered separately. “Ideally one would receive a single vaccination and some of the material wouldn’t release until later,” says Schief.

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Earlier this year, his team reported of the first primer designed to stimulate B cells. Now, his team has tested one of the later boosters in another small trial.

When volunteers were given mRNA coding for the HIV outer protein in a form that gets incorporated into cell membranes, 80 per cent produced antibodies that lab tests show are capable of blocking infections.

In this trial, these antibodies were specific to one strain. The researchers hope when the booster is given as part of the sequence, so that each component is produced inside the body in the right order, it will generate a broader response.

However, in both trials, a higher-than-expected number of the volunteers developed hives, or urticaria, which in a few cases has persisted for years. This issue hasn’t arisen in other mRNA vaccine trials, nor in non-mRNA vaccines containing the HIV protein, Schief says. There seems to be something about delivering the HIV protein via mRNA that can trigger this side effect. “It is a scientific mystery at the moment,” he says.

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“Not knowing what causes this adverse effect means that it will be hard to prevent,” says , a vaccine expert now at a company called in Morocco.

Ertl agrees mRNA technology allows for rapid testing of vaccine components, but thinks the final product may be best delivered by a different type of vaccine, such as those made using empty viral shells. These vaccines can be stored at room temperature, for example, rather than requiring refrigeration, she says.

There is now a drug called lenacapavir that provides nearly complete protection against HIV infection with two injections per year. However, Schief thinks a vaccine is still needed. “We’re all aiming to make it as quickly as possible,” he says, but even with progress being sped up by mRNA technology, an approved HIV vaccine is probably still decades away.

A genetic variant found only in people of African ancestry may offer them considerable protection against HIV. A better understanding of this could improve treatments for the infection among these populations.

Unique to people with African ancestry, up to 13 per cent of such people are thought to have this variant. Among people with HIV, the viral loads of those with this version of the gene are 20 times lower than those of people who are also of African ancestry, but lack the variant. As a result, the former have slower HIV progression and a reduced risk of transmitting the virus, says at the University of Cambridge.

This is the first time a genetic variant related to HIV has been found in three decades, says Groom. It is also of particular significance since it is specific to people with genetic ties to Africa, where most of the world’s HIV cases are found, she says. Advances in treatment have reduced the spread of HIV since it was discovered, however, the virus easily mutates and evades the effects of drugs, says Groom.

Most genetic research on HIV has focused on people of European descent, which led to the discovery of variants associated with a reduced viral load about 30 years ago. Those variants, found on two genes known as HLA and CCR5, account for about 15 per cent of the differences in HIV viral loads among people of European ancestry.

Now, at the National Microbiology Laboratory in Canada and his colleagues have compared the DNA of 2682 men and women of African ancestry, most of whom were African Americans. All were positive for HIV-1, the most common form of the virus.

The researchers found that the participants’ viral loads were somewhat associated with variants on the HLA gene, but not the CCR5 gene. However, unlike in people of European ancestry, they also found a relevant variant in a different gene, known as CHD1L. This gene is in a region of chromosome 1 that is known for encoding proteins involved in DNA repair, says Groom. All humans have this gene, but only people of African ancestry carry the newly discovered variant.

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To confirm their findings, the researchers searched for the CHD1L variant in an additional 1197 people of African ancestry who were living with HIV-1 in multiple countries. They found that those who have the variant – an estimated 4 to 13 per cent of people of this ancestry – have significantly lower viral loads when infected with HIV-1, says Groom.

Wanting to understand how the variant affects HIV loads, at the University of Cambridge and his colleagues, including Groom, experimentally switched it off in genetically modified human immune cells in the lab, before exposing them to HIV-1.

Over many trials, the team found that the virus replicated much more in one type of immune cell – macrophages – when the variant was switched off than when it wasn’t. Surprisingly, however, that wasn’t the case for another type of immune cell, T-cells, even though these are thought to be where most HIV replication usually occurs, says Groom. More research could shed light on the role of macrophages in HIV replication, she says.

Combined, the findings could, over time, lead to more-targeted management and treatment of HIV in people of African ancestry, says Groom.

A 53-year-old man in DĂŒsseldorf, Germany, has been declared cured of HIV by doctors after a blood stem cell transplant to treat leukaemia – the third case of this kind.

The man has no signs of active infection four years after he stopped taking antiretroviral drugs. “We don’t think there’s a functional virus present,” says at DĂŒsseldorf University Hospital.

The “DĂŒsseldorf patient” tested positive for HIV in 2008. In 2011, he developed leukaemia that was treated with chemotherapy, but it came back the following year. So, in 2013, the blood stem cells in the man’s bone marrow that give rise to immune cells – including the cancerous ones – were killed off by chemotherapy and then replaced with donor blood stem cells.

Crucially, doctors found a donor with a mutation that disables the CCR5 receptor that HIV uses to infect immune cells. This transplant made the man’s immune system HIV-resistant.

In 2017, the team was able to stop giving him immunosuppressing drugs to prevent rejection of the donor cells and, in November 2018, antiretroviral treatment was halted.

Two other people treated for cancer have previously been reported to have been cured of HIV in the same way. However, because bone marrow transplantation is risky, and given that drug treatment can keep the virus in check, this will never be used to treat HIV alone.

One alternative approach that is being explored is to use gene editing to mutate the CCR5 gene in the immune system of people who are HIV-positive.

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