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(Photo: Sebastian Kaulitzki/Shutterstock)

Why the HIV Vaccine Is Not a Pipe Dream

• January 10, 2014 • 8:00 AM

(Photo: Sebastian Kaulitzki/Shutterstock)

Despite 30 years of failure on an evolving viral puzzle, there’s reason to believe we’ll one day live in a world without HIV.

It’s no secret that HIV is among the most devastating viruses plaguing humanity today. The World Health Organization puts the number of HIV deaths so far at more than 36 million people. Another 35 million are currently infected, including one in 20 adults in Sub-Saharan Africa. But don’t we know how to prevent viral infections? We have effective vaccines against many viruses. Why don’t we yet have one for HIV?

With an effective vaccine, we could make HIV join the ranks of formerly fearsome viruses that are now gone in most of the world—like the viruses that cause polio, smallpox, and measles. Considering the damage that viruses cause, an effective vaccine is a stunningly simple and reliable means of preventing death and suffering. When an effort to remove a bat colony from our home went wrong a few years ago, my family went to the clinic for our rabies shots—and then out for ice cream. We all slept well that night, knowing that, while rabies is fatal, it is also 100 percent preventable thanks to a vaccine. A vaccine that made HIV infections as preventable as rabies or polio would be one of the century’s greatest medical and humanitarian successes.

While we’ve been hearing promises about a vaccine for three decades, many recent insights into the immune escape mechanism of HIV result from the applications of new DNA analysis technology that has come online only within the past five years.

There is no effective HIV vaccine, but that’s not for lack of effort. After three decades of intense study, researchers have recognized that HIV presents challenges that are “unprecedented in the history of vaccinology.” Fortunately, there is reason for optimism. Within just the past five years, new biotechnologies have resulted in major breakthroughs in our understanding of HIV’s vulnerabilities. Before these recent developments, some researchers wondered whether an effective vaccine would ever be possible. Now, although a workable vaccine may not be exactly just around the corner, scientists have strong reasons to believe that we will eventually have one.

Most vaccines against viruses work by prompting our bodies to produce antibodies that latch on to and neutralize the virus. Figuring out where on the virus to target antibodies is a critical issue in the development of a vaccine. A vaccine is like the scrap of clothing investigators use to put a bloodhound on to a fugitive’s scent; by presenting specific viral fragments, a vaccine trains your body’s immune system to recognize the virus. A key challenge is to include the right viral parts in the vaccine, so that the immune system makes antibodies that effectively target and broadly neutralize all of the different mutational forms of HIV.

To be effective, an antibody has to target a part of the virus that is 1) critical to virus function and 2) easily accessible. Unfortunately, in the case of HIV, some critical parts of the virus are unusually well hidden and inaccessible to most antibodies. More importantly, many critically functional parts of the virus are hard to pin down. HIV is able to rapidly evolve new variations of important components in a nanoscale Houdini act called “mutational escape,” becoming a moving target for the immune system.

After several decades of little progress on a vaccine, many researchers had begun to doubt that broadly neutralizing, anti-HIV antibodies were possible. But in 2009, using new technologies to isolate and copy antibody-producing cells from HIV-infected patients, two groups of researchers discovered potent, broadly neutralizing antibodies. By showing that such antibodies exist, these studies gave researchers renewed hope that a vaccine against HIV is indeed feasible.

WITH THE DISCOVERY OF potent antibodies against HIV, researchers have been able to focus in on the details of how HIV evades the body’s defenses, with the aim of identifying new weak points that can be targeted by a vaccine. A study released in December, led by researchers at the National Institutes of Health Vaccine Research Center, identified a critical part of the virus that appears to play an important role in the mutational escape process. The researchers exposed vaccinated macaques to a mixture of different strains of the monkey version of HIV, Simian Immunodeficiency Virus (SIV). They found that a particular pair of mutations in SIV allowed the virus to evade vaccine-induced antibodies, and, remarkably, those mutations had the same effect on HIV. The researchers concluded that they had discovered signs of “a fundamental mechanism of immune escape.”

Discoveries like this will help researchers focus their vaccine-design efforts, especially in the aftermath of another failed HIV vaccine trial in 2013. It’s worth noting that, while we’ve been hearing promises about a vaccine for three decades, many recent insights into the immune escape mechanism of HIV result from the applications of new DNA analysis technology that has come online only within the past five years, and so we should stay optimistic.

Even without an effective HIV vaccine, worldwide public health efforts are making a dent in the death toll of HIV. Thanks to better therapies, more people are living with HIV, rather than dying from it. The heroic humanitarian efforts that have made these therapies available to nearly 10 million people deserve our admiration. But we shouldn’t give up our hope for a world in which HIV becomes a disease of the past, eliminated with a simple, inexpensive, but effective vaccine.

Michael White
Michael White is a systems biologist at the Department of Genetics and the Center for Genome Sciences and Systems Biology at the Washington University School of Medicine in St. Louis, where he studies how DNA encodes information for gene regulation. He co-founded the online science pub The Finch and Pea. Follow him on Twitter @genologos.

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