The HIV vaccine is missing.
The vial hasn’t been stolen from a lab in a case of white-coat sabotage — this is not the type of mystery in which authorities would ring up Hercule Poirot, Agatha Christie’s world-renowned sleuth, and hire him to solve the case.
It’s missing not because it has been stolen, but because it has not yet been developed.
And for the 33.2 million that the United Nations’ latest epidemic update projected are living with HIV, the precursor to AIDS, worldwide, this may not be too comforting.
However, this doesn’t mean scientists and pharmaceutical engineers are neglecting the task; in fact, according to Fred Fuller, professor virology, researchers must work around two obstacles — HIV’s resistance to certain vaccines and the FDA’s refusal to legalize a vaccine that contains live strains of the virus.
“Work on the development of an AIDS vaccine [has been under way] for almost two decades,” said Fuller, who sits on the AIDS Vaccine Study Section panel for the National Institutes of Health. “As soon as they were able to isolate the virus in the 1980s people thought, ‘Well great, now that we know what the virus is we’ll have a vaccine in a couple of years.’ But the virus didn’t behave like we thought it would behave. It’s been almost 20 years since we’ve been able to identify virus because we’ve reached that snag.”
The “snag” Fuller mentioned is this: unlike viruses such as chicken pox, HIV cannot be treated by killed vaccines. For reasons Fuller said researchers cannot yet explain, the virus only reacts to attenuated live vaccines.
Model systems, he said, have been used to estimate how attenuated live cultures will affect humans. In the models, researchers test the effects of monkeys naturally infected with Simian Immunodeficiency Virus — the closest model to HIV. By treating them with attenuated live vaccines, they researchers can examine the vaccines’ immune responses in the monkeys.
“In that model, the attenuated live vaccines have provided the most promising protection. However, there are safety concerns with very good reason because they have been shown to cause disease in the monkey model system even though they’re attenuated,” he said. “But as long as [the virus] can replicate, it can mutate — giving it has the potential to cause disease.” Thus, researchers are facing a wall — one that is blocking them from both proceeding with live vaccines and one that the FDA won’t allow them to tear down.
In the shadow of this barrier, scientists have begun investigating a different solution.
“They’re trying to learn how the attenuated live vaccine works, and try to mimic it with safer vaccine approaches,” he said. “Hopefully we have the capacity to mimic it. But first we have to learn what immune responses we need to mimic.”
His hesitance arrives in the form of unidentified “corrolates of protection” — such as a specific T- or B-cell — that is effective in killing the virus or virus-infected cells.
The question researchers must answer, he said, is why those immune responses take effect when exposed to the attenuated live, and not killed, vaccines.
Fuller’s peers, who present to the panel their proposals for HIV vaccines in attempts to receive funding from the National Institutes of Health, have demonstrated their willingness to side-step real attenuated live vaccines and find both the answer to this question and the vaccine that will hinder HIV from ever infecting a potential host.
According to Gregg Dean, professor of molecular biological sciences and member of the NIH’s AIDS Immunology and Pathogenesis Study Section panel, the vaccine is imperative to eliminate viruses from the population.
“If you look at the history of viruses in humans, none of them have been eliminated without a vaccine,” Dean said. “We don’t see cases of smallpox because everybody was vaccinated for it.”
And through research, he said, scientists have learned “quite a lot” about what is successful and unsuccessful about each vaccine manufactured and tested.
“It’s going to take an innerative nature to develop the vaccine,” he said. “It took 30 to 40 years to develop vaccines for other viruses, so it’s not terribly surprising that it’s taking us a while to develop a vaccine for HIV. The virus is very clever and the immune system is very complicated.”
However, the absence of a vaccine doesn’t indicate a lack of strides taken toward solving the problem.
“It’s the most complex disease we’ve ever attempted to develop a vaccine against,” he said.”There have been quite a large number of clinical trials. None of them have shown any positive results, so that’s depressing. We take what we know and we make our best guesses. We look for weaknesses in the viral life cycle, we look for strategies that we know the body uses naturally to defend itself against a virus. We’re trying to encourage those responses with a vaccine.”
Uncovering a vaccine for a virus that is both complicated and deceitful is a difficult process, he said, but one through which researches are willing to undergo to find an answer.
“We can test these things in the lab and in animal models — and that’s how these things are being investigated,” Dean said. “It’s a slow process and painful because sometimes the most elegant ideas fall flat on their faces.”
But it’s not been in vain; with each step researchers take, they learn more about the virus and ways to suppress it.
“What we’ve learned [from vaccine research] is that HIV is very complex. We’ve been trying to understand the virus, trying to understand the immune system,” he said. “The virus and immune system interact in many different [ways]. There’s not a simple explanation.”
Part of understanding the virus involves studying similar, natural models in animals such as monkeys and cats. SIV-infected African green monkeys, Fuller said, never develop a disease from the virus — there have been no cases of death related to the virus or its resulting disease.
However, he said if the monkeys were to be introduced to a foreign strain of SIV, it would result in disease.
This pattern can be applied to humans as well, he said. Once the foreign virus was introduced to people, it eventually developed into AIDS. Over time, however, the virus might find it more profitable to stay in the host’s body longer — in order to have more time and opportunities to transmit the virus, which Fuller said is already difficult to transmit.
The virus could find it even more beneficial, he said, to keep the host alive by not developing into a disease. Acting in accordance with the Darwin’s theory, the virus that survives the longest will have a better chance of spreading and mutating.
But researchers need not travel to Africa to complete these studies. Mary Tompkins, professor of pathobiology, works with Feline Immunodeficiency Virus — the natural strand of the virus found in cats — at the College of Veterinary Sciences to delve further into exactly how the virus suppresses the immune system.
“We still don’t understand how the virus suppresses the immune system,” she said. “We know a number of things that it does, what it does to the immuneresponse, but we still don’t have a good understanding of why the immunesystem can’t get rid of the virus.”
And they’ve unveiled some new information.
“We know that the virus activates some cells that are designed to keep the immunesystem in check [they tell the immune system, ‘OK, you’re all finished. Take a rest.’] so that it doesn’t induce tumors,” she said. “They’re turning that message on early before the immune system has actually cleared the virus.”
With these models, researchers can get closer to understanding the virus and the disease that ravage the human body. And even though the UN’s report showed a decrease in the amount of new HIV infections, as well as a decrease in global AIDS-induced deaths, Dean said that does not indicate that the disease is “just going to continue to go away.”
“That would take a long time, and it’s not something that we’re willing to accept because of the huge cost of human life,” Dean said. “The number of infections may be declining, the number of new cases may be declining, but if there were to be an emergence of a new variant you’d see an inflation.
“Maybe we’ve seen it peak out but it doesn’t eliminate the need for us to continueto react socially to modify behavior, to continue to develop effective therapies and, ultimately, to develop a vaccine.”
