“We hope to have a vaccine ready for testing in about two years. Yet another terrible disease is about to give way to patience, perseverance and outright genius.”
That is what Margaret Heckler, the US Secretary of Health, said about the HIV epidemic in 1984.
But four decades and some 40 million deaths later, the world still has no vaccine to protect against HIV.
Last week, Johnson and Johnson became the latest pharmaceutical firm to pull out a potential contender.
The US company announced that its vaccine, the world’s only candidate still in late-stage trials, was ineffective.
The study, known as Mosaico, tested the injection in 3,900 men and transgender people across North America, South America and Europe. But while analysts thought it was safe, the trial was stopped because the vaccine was no more effective at preventing HIV infections than a placebo.
It is yet another blow to an important field of research that has become accustomed to disappointment.
To date, eight HIV vaccine candidates have reached the final stage of clinical trials. All have failed at the last hurdlewith only one showing signs of modest efficacy in a trial in Thailand between 2003 and 2006.
Johnson and Johnson tried to build on the modest success of the Thai study, but in the end it just didn’t work out.
So why is it so hard to develop a vaccine against HIV? After all, scientists had developed a jab for Covid and were in trials within months of the virus emerging.
‘No one is cured of HIV’
Experts are still confident that they will one day produce a successful HIV vaccine, but they point to some formidable challenges that still need to be overcome.
Perhaps most notably, there is no “nature road map” that scientists can copy or improve on.
“When we get measles, we recover from the measles and there’s an immune response that our body builds, [and we can design a vaccine] that copies that response,” says Professor Salim Abdool Karim, director of the Center for the AIDS Program of Research in South Africa.
“No one has recovered with HIV. There is no immune response that occurs naturally. Nature has nothing we can copy.”
He added that when Sars-Cov-2 emerged, previous research into the first Sars outbreak had already identified which part of a coronavirus to target — the so-called “spike protein.” But this is not the case with HIV.
“Even though we have the technology to make a vaccine, we don’t know what [part of the virus] it has to make,” Prof Karim said.
The HIV virus also lurks in chromosome CD4 cells, where it is not easily visible to the immune system,” said Tomáš Hanke, a professor of vaccine immunology at the University of Oxford, who has worked on HIV vaccines for 30 years.
He added that the pathogen’s genetic makeup is also changing rapidly — much faster than Sars-Cov-2, the Covid virus. This means that by the time you create a vaccine to fight it, the virus may have already left.
And finally, said Prof. Karim, there is no reliable animal model that can serve as a basis for HIV virus research.
“We have these real problems that make an HIV vaccine so, so difficult,” he said.
But the optimism remains.
“[The latest setback] is disappointing, but the positive thing is that we have learned”, says Prof. Hanke. “[The Johnson and Johnson vaccine] was designed several years ago, when perhaps we knew less. But the trial confirmed that some ways of using T cells and antibodies just don’t work, and we have a good idea of how to improve this.”