For around 30 years we have lived under the spectre of HIV. In the early 1980s, the mysterious appearance of symptoms that would later be known as AIDS led to unprecedented efforts to unmask the cause. On 23 April 1984, Margaret Heckler, the US Secretary of Health and Human Services, told the world that scientists had identified the virus that was the probable cause of AIDS. She was correct. She also said that a vaccine would be “ready for testing in approximately two years.” She was wrong.
Despite 28 years of research, there is still no vaccine that provides effective protection against HIV, and in that time around 25 million people have died of HIV-related causes. To understand why creating a vaccine is so hard, you need to understand HIV. This is no ordinary virus. Scientists who study it speak of it with a mix of weary frustration and awed reverence.
The virus is the most diverse we know of. It mutates so rapidly that people might carry millions of different versions of it, just months after becoming infected. HIV’s constantly changing form makes it unlike any viral foe we have tried to thwart with a vaccine. “Almost every vaccine that’s been developed protects against a small number of strains,” says Gary Nabel, Director of the Vaccine Research Center at the US National Institute of Allergy and Infectious Diseases (NIAID).
Vaccines train the immune system to recognise part of a virus, creating a long-term armada of antibodies that seek and destroy the invader, should it ever show its face. For HIV, the most obvious target is gp120, the surface protein that it uses to attach itself to human cells. But gp120 also constantly changes shape, making it difficult to recognise. It also comes in clusters of three that are shielded by bulky sugar molecules, hiding it from the immune system.
On top of that, HIV targets immune cells, the very agents that are meant to kill it. And it can hide for years by shoving its DNA into that of its host, creating a long-term reservoir of potential infection.
So, creating an HIV vaccine is like trying to fire a gun at millions of shielded, moving targets. Oh, and they can eat your bullets.
Uphill struggle
So far, nature has provided little reassurance that a vaccine against HIV is even possible. For virtually every other microbe, there are people who naturally recover from their infections. “Nature itself provides the proof-of-concept experiment. It has told you that the body can inherently do this,” says Anthony Fauci, an immunologist who heads NIAID. But when it comes to HIV, “we have the astounding reality that, with more than 30 million people living with the virus, there is not a single documented case of someone mounting an immune response to completely eliminate the virus from their body.” Some people have the right genetic qualities to keep the virus in check, but no one clears it.
Given these challenges, it should be no surprise that vaccine research has been, to quote one researcher, a “Sisyphean onslaught of disappointments”. Only three potential candidates have made it through clinical trials. Vaxgen’s AIDSVAX vaccine, consisting of two fragments of the gp120, failed to provide any protection. Merck’s v520 vaccine, consisting of a harmless cold virus carrying three HIV genes, fared even worse. It was meant to marshall immune cells called T-cells to kill off infected cells. It failed. Worse still, the trial had to be stopped early because vaccinated people seemed to be more susceptible to infections, for reasons we still do not fully understand.
