Johnson & Johnson became the latest company to have a failed vaccine trial against HIV last week. While it was a great disappointment to many, efforts continue in this space, helped by recent Covid-19 vaccine advances.
HIV has been around for decades. While antiretroviral treatments have improved enormously, turning what was once a death sentence into a chronic condition, an effective prophylactic vaccine has proved elusive.
One reason it’s so difficult to develop a vaccine for HIV is that the virus mutates very quickly.
“HIV has a tremendous amount of variability,” said Kimberly Smith, Head of R&D at the UK company ViiV Healthcare, which develops treatments for HIV infections. “When we talk about the coronavirus that’s the cause of Covid-19, we talk about the various variants, which right now are just a handful. But HIV is literally hundreds, perhaps thousands of times more variable than the coronavirus.”
Another challenge facing vaccine makers is that HIV can escape immune detection. “When HIV comes into the body, it goes into a cell and hides there and is silent to the immune system; the immune system doesn’t see it as foreign and doesn’t react to it as rapidly,” added Smith.
The closest anyone has come to developing an effective HIV vaccine was a collaboration involving the US Army and the Thai Ministry of Health. In 2009, the partners completed a phase III trial testing a combination of two viral vector vaccine candidates that had previously failed on their own, one from Sanofi and another from the US firm VaxGen. While the trial was not successful enough to achieve approval of the vaccine, it did reportedly reduce infection rates by 30%.
Since this trial was completed, several companies and other research teams have tried to replicate these results with little success. For example, a Sanofi/GSK trial testing an adapted version of the vaccine regimen in South Africa failed last year. Reasons for the different outcomes aren’t clear, but one suggestion was that South Africa had a higher rate of HIV infection than Thailand, which overwhelmed the vaccine’s protection.
Last week’s ill-fated trial from J&J involved a different type of vaccine delivered using an adenovirus vector — similarly to J&J and AstraZeneca’s Covid-19 vaccines. The vaccine was tested in a phase IIb trial in 2,600 young women in five African countries: Malawi, Mozambique, South Africa, Zambia, and Zimbabwe.
After 24 months of follow-up, the J&J candidate vaccine prevented only around 25% of HIV infections. While no significant adverse effects were seen, the low efficacy means the trial will not continue.
Another phase III trial testing a different composition of the vaccine is also ongoing. The outcome could be different as the participants of this trial are men who have sex with men and transgender individuals. Additionally, the study is being run in America and Europe, where the most common strains of HIV are different from those in Africa.
A representative from J&J told me that the firm is assessing the data from the failed trial in more detail: “We will work to ensure that key learnings… are shared with the public and scientific community, including our colleagues in the field of HIV vaccine research.”
In the last few years, there have been widespread setbacks for companies developing both vaccines and treatments for HIV. Last year, for example, a phase III trial of an HIV vaccine developed by the US-based HIV Vaccine Trials Network met with failure. In the same year, the French firm Abivax postponed its HIV treatment program indefinitely in favor of targeting chronic inflammatory diseases. In the previous year, the German company Mologen dropped the development of a drug for HIV when it filed for bankruptcy.
Despite these setbacks, ViiV Healthcare raised hopes in the HIV space earlier this year with the FDA approval of monthly antiretroviral injections that can replace daily pills to control HIV infections. Smith says that investments in the HIV sector seem to be increasing: “As more effective treatments became available, there was a time when fewer companies were investing in HIV, but I think we’ve turned the tide.”
The massive focus on Covid-19 vaccine development over the last year may also hold benefits for those setting their sights on an HIV vaccine.
“It had a positive effect in the sense that technologies used to fight Covid-19 such as mRNA or adenoviral vectors are now rolled out with ease to fight other viruses including HIV,” says Frederic Garzoni, CEO of UK-based vaccine startup Imophoron, which is developing its own Covid-19 vaccine candidate. “What we are learning for Covid will hopefully one day be instrumental to combating and defeating HIV.”
Indeed, Moderna, the developer of one of the mRNA Covid-19 vaccines marketed in the US and EU, posted information last month showing it is entering phase I trials with an mRNA-based HIV vaccine.
Despite growing interest in the vaccine space, however, creating a prophylactic vaccine against a virus like HIV remains a huge challenge.
“HIV has massive glycosylation, meaning sugar chains, around viral surface proteins which are called glycoproteins. That acts like a cloak and shield which masks the virus from the immune system,” says Garzoni.
“Your immune system cannot see HIV and if it does, then HIV mutates. It is a powerful double punch which HIV has evolved over the years to mock and defeat the immune system, and very successfully so.”
This article was updated on 9 September 2021 with a correction that ViiV’s approved HIV injections are monthly. Cover image via Anastasiia Slynko