HIV Vaccine: Do Babies' Immune Systems Hold the Key?
Researchers have discovered peculiarities in a baby’s immune system which might lead to the end of HIV.
HIV/AIDS research has come a long way. Though first introduced to human hosts in West Africa at the turn of the previous century, the first case of HIV/AIDS wasn’t recorded until 1959. Yet, it didn’t enter into the collective psyche until 1981, when gay men were mysteriously dying from a disease which gave pneumonia-like symptoms, before compromising their immune systems and taking the their lives.
By 1994, AIDS was the leading cause of death among those ages 25-44. Luckily a year later, highly active antiretroviral therapy (HAART) were discovered. They made it to market by 1997. This is a mix of medications which stops the virus from replicating. In 2012, a prescription medication called Truvada was made available, though it still isn’t being marketed. Also known as pre-exposure prophylaxis (PrEP), the drug can bring one’s viral load down so low it is undetectable. It can also prevent the transmission of HIV, if taken regularly.
Truvada also known as PrEP or antiretroviral drugs (ART).
Though we can prevent HIV from turning into full-blown AIDS, we cannot cure it. The virus hides in areas of the body known as reservoirs, biding its time, and looking for an opportunity to resurface. What’s more, even though patients on these drugs can live normal, healthy lives, a recent study found that HIV patients on such drugs experience severe age-related diseases, such as heart disease and cancer, five years earlier than their peers. A few novel approaches are out there, including a strategy known as “kick and kill,” which pushes the virus out of its hiding spot and eliminates it. Still, we are still far from a cure. This is truly one of the most complex diseases medical science has ever faced.
Besides a cure, the other approach would be a vaccine. But this too has proven elusive because adult immune systems respond much too slowly to the virus. By the time protection has been built up, the virus has already countered it. Now a team of researchers from the Fred Hutchinson Cancer Research Center in Seattle, believe they have a way of devising one. Studying the immune systems of infected infants, researchers believe that if they can mimic a baby’s immune response, they may be able to create the world’s first HIV vaccine.
Model of the HIV virus.
Published in the journal Cell, researchers studied babies born to infected mothers in Kenya, years before antiretroviral drugs were available. They found that broadly neutralizing HIV antibodies can be detected in infants within a year after becoming infected. Not only do the antibodies need to be produced quickly, there has to be the right mix of them to identify and eliminate the virus. The immune system must also be able to quickly adapt to the virus. Thus antibodies, which have passed through the process of "somatic hypermutation," are required. This is the ability to block and bind to pathogens, an essential part of the immune response.
It can take years or even decades for an adult immune system to mount a response capable of protecting the body against HIV. Due to this, a vaccine has been impossible to create. This study builds upon a previous one which discovered, unexpectedly, that broadly neutralizing antibodies were in fact created early on in life. Not only can the infant immune system produce such antibodies in less than a year, a vaccine could be culled from this with less finagling than previously thought. Though this is great progress, there is still a long way to go. A vaccine needs to be able to trigger an immune response within months of infection, not a year or more.
HIV virus (in green) attacking immune cells.
Researchers used blood samples from infected infants, who were part of a breast feeding study within the Kenya Research Program. The Seattle team examined antibodies and the antibody response within the infants’ blood. One baby in particular was HIV-negative birth. It was found to be infected by four months of age, perhaps due to breastfeeding.
Dr. Julie Overbaugh was the senior author in this study. She leads a lab within the research center which investigates HIV transmission and development. Dr. Overbaugh said that adults have immune responses driven by one specific kind of antibody. However polyclonal responses, or those with several different kinds of antibodies, are harder for the virus to avoid. It is also much more difficult to protect itself from. So not only was a baby’s immune system faster, it approached HIV in a multi-faceted way.
HIV infection rates globally.
The team also found that infant antibodies target different sites on HIV than adult ones do. This might suggest a unique kind of protection occurring in early life. Dr. Overbaugh and her team say that these quickly-produced, broadly neutralizing antibodies could lead to a vaccine. Even so, this breakthrough leaves more questions than answers.
For instance, why exactly was the immune response different in babies? And why are these unique features lost later on in life? One theory is that the infants were already exposed to the virus through the mother’s immune system, giving them the upper hand after birth. Otherwise, it may turn out that babies have an immune system capable of providing extra protection in early life. More research will be needed to confirm these results, and to further understand what forces are at work. But researchers are optimistic that a vaccine may someday soon be within reach.
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The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?
But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.
What's dead may never die, it seems
The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.
BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.
The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.
As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.
The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.
"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.
An ethical gray matter
Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.
The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.
Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.
Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?
"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."
One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.
The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.
"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.
It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.
Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?
The dilemma is unprecedented.
Setting new boundaries
Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."
She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.
Some back story
A Dunbar Correlation
Professor Dunbar's response:
Friendship, kinship and limitations
Gray matter matters
There is an eclectic list of reasons why compassion may collapse, irrespective of sheer numbers:
In the end
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