New genetic analysis narrows HIV vaccine targets

CROSS-POSTED from Nature Medicine’s Spoonful of Medicine

By Kathleen Raven

September 10, 2012

The road to a protective HIV vaccine has not been easy thus far. The failed STEP trial, halted in 2007, was just one major trip-up among several, and two years later the massive RV144 trial from Thailand spurred controversy about efficacy rates. Part of the problem is that researchers have long struggled over the best target for the HIV vaccine.

A study published online today in Nature from researchers in the US and Thailand should help scientists inch closer to settling that debate. Through genetic analysis, the study suggests that specific amino acid sequences found in the HIV V2 protein loop—there are five total loops on the outside of the viral envelope—could lead to improve vaccine effectiveness.

PHOTO BY tonrulkens Flickr, Creative Commons. Please click on the photo to see the original source.

The current RV144 vaccine contains three synthetic HIV genes.

One, called the ENV gene, produces the ‘envelope’ (Env) protein loops. To understand how the vaccine exerted influence on the virus, the researchers sequenced more than 1,000 HIV virus genomes from 110 ‘breakthrough’ viruses isolated from 44 vaccinated participants and regular viruses found in 66 placebo recipients.

The analysis centered on the idea that viruses that ‘break through’ vaccine protection contain a genetic signature, visible by changes in the amino acids chains they encode, compared with viruses the vaccine fends off. “Viruses that escape [the vaccine] carry the scars of the immune response,” explains Jerome Kim, a virologist at the US Military HIV Research Program (MHRP) in Silver Spring, Maryland and senior author on the paper. Based on the frequency of virus sequences in the two groups, he and his colleagues calculated that when the HIV virus and the vaccine code for the same 169 amino acid position, the vaccine is 48% effective. However, the vaccine is estimated to be 80% effective when the virus and vaccine sequences match at position 169 and—unexpectedly—do not match at position 181.* The overall efficacy rate in the original RV144 trial hovered at just 31%.

The finding raises the possibility that a future, retooled vaccine (especially one to fight the HIV virus subtype E found in Thailand) could contain an HIV envelope gene engineered to present the V2 protein loop in a way that would prompt a more effective antibody and overall immune response.

The new study also provides an independent confirmation of a correlative study published in April in the New England Journal of Medicine, which suggested that when the body produced antibodies geared toward the V2 protein loop, the result was lower rates of HIV infection. “We know that the vaccine induces antibodies, those antibodies exert some immune pressure, and so we expected to see the consequences of that pressure on the [HIV] viruses,” says Morgane Rolland, a virologist at MHRP and study co-author.

“I am cautiously optimistic [about the results],” says Andrew McMichael, an immunologist at the Weatherall Institute of Molecular Medicine in Oxford, UK, who was unaffiliated with the study. He says he is optimistic that this study confirms that V2 antibodies may play an important role in preventing HIV infection. However, McMichael points out that the mutation of the amino acid position 181 was mostly found in viruses of the placebo participants and therefore may be difficult to link to a V2 antibody response since those patients did not receive the vaccine.

But Barton Haynes, an immunologist at Duke University School of Medicine in Durham, North Carolina, and senior author of the NEJM study earlier this year, thinks research on a vaccine from the RV144 trial is moving ahead like clockwork. “It adds support to the hypothesis that these V2 antibodies may in some manner be involved in protection,” he says. The next step, which should happen soon, he says, would be to try out a retooled vaccine with this added antibody protection in macaque monkeys.

*CORRECTION: An earlier version of this post incorrectly stated the vaccine is 80% effective when the virus and vaccine sequences match at amino acid position 181. Researchers are still studying to understand how a mismatch at this site might be beneficial.

ScienceOnline 2012 – Behind the #scio12 hashtag

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In 2005, two bright-eyed friends, sipping coffee in North Carolina’s Research Triangle, hatched a plan. Why not gather professionals and amateurs of all stripes, under the heading “science online,” in a cozy space with free-flowing caffeine and see what happens? Bora Zivkovic and Anton Zuiker (later joined by Karyn Traphagen) could not have known that the wire they tapped would explode to life. Seven years later—a short time period in the life of any conference—ScienceOnline has morphed from an obscure meeting to an event worthy of a mention in The New York Times and a post on BoingBoing. With the latter being, perhaps, a bigger deal.

 

The reason the ScienceOnline conference—or “unconference,” the category its organizers prefer (it is better nomenclature, you’ll see)—rocketed to recognition might have something to do with the possibilities on hand each year. The party thrown last month at North Carolina State University’s McKimmon Conference Center was no exception. For example, conference-goers could strap their mobile devices and laptops onto one of the fastest broadband Internet connections in America. Ready, set, tweet! If you were torn between which concurrent session to attend, your heart leapt at the realization that your colleagues, equipped with otherworldly tweeting abilities, actually live-tweeted every single session, dutifully including the appropriate hashtag—#scio12—on each tweet. With such insightful tweeting, a person really could be in two places at once. Other possibilities included: feeling surprisingly intimate with the 449 other conference attendees; delightfully drowning yourself in more information than you ever thought possible; marveling at the on-the-fly art produced by talented artists; and, certainly not least, taking home important lessons about communicating medicine and science to the public.

 

Wait, we’re talking about a conference/unconference, right? Doesn’t this seem a bit… hyperbolic? You should ask Paul Raeburn of Knight Science Journalism Tracker that question. (Hint: He would probably agree the hype is fair and warranted.) And if so many people are pumped about the conference, then why only 450 total attendees? And now we arrive at one of the most rare and gifted qualities of this particular conference: you don’t have to physically be there to share and participate in the excitement and learning. Ideally you are there, sharing a pint with a fellow blogger or discussing the merits of citizen science over a muffin at breakfast. But anyone who’s interested in science online can get involved. Now. The ScienceOnline 2013 planning wiki is already posted!

 

Another attribute of the annual event that contributes to its “unconference” nature is the lack of a common, overarching theme. This translates to wide and varying session topics—from science tattoos (yep, Carl Zimmer wrote the book on ‘em) to preserving digital science online. The professionals and amateurs that Anton and Bora originally targeted can still choose from the dim-sum of science-related topics available. The variety also makes summarizing the contents of ScienceOnline quite difficult. Instead of more description, I’d like to make a prediction: Science journalists will be seeing (and doing) more reporting based on data journalism and the semantic web. Two recent graduates from New York University’s science writing program showcased the possibilities of how to turn data into art during one session. In another discussion, two researchers described a Matrix-like world behind the world wide web: the Semantic Web. Here’s an example of Semantic Web in action. If you’re curious to learn more about ScienceOnline, be sure to check out a complete listing of the conference experience here.

 

This was my second consecutive year attending the three-day mad dash. And there’s something extremely reassuring about the classic, core values that continue to be the force behind excellent science communication online: writing/video/audio should be clear, factual and compelling

Mourning loss of water (good-tasting)

I’ll be the first to tell you: I’m a water snob.

You would be, too, if you grew up drinking pure groundwater preserved in sediment rock. This isn’t Evian, which, frankly has a stale finish. I’m not talking about Fiji and that bottled brand’s clean but flat taste. The water that nourished me for 18 years tasted like underground, undiscovered Eden. You couldn’t bottle that sweet, dewy, unmistakably fresh water. I knew what pristine tasted like and as long as I could get it, I would have it.

When I moved back to live in Athens, Georgia, about a 20-minute drive from the homestead, I insisted on getting that water again.

Beginning in earnest last year, I made weekly trips to my parents’ home under the auspices of a visit. But with 20 empty glass bottles clinking together in bags on my shoulders, I couldn’t hide the fact that my appearance was partially prompted by a low water supply.

So my parents smiled at my hardheadedness and we joked about my “water problem” and I happily quenched my thirst during the week with the water I’d grown up with. Given the extra effort to get this water, I didn’t necessarily take it for granted. I also didn’t think the water could possibly change. I was pessimistic enough to think that what is happening in Australia would probably happen in due time to the southeastern United States. But even that bad-case scenario was years off.

Or so I thought.

A little over one week before Christmas Day, the well pump at my parents’ home clogged up with years of soil minerals and sputtered to a stop. The next day two well repairmen maneuvered heavy equipment over to the simple well pump structure. They tore up the old pipe, replaced the filter, and then dumped Clorox into the water supply to (ironically) prevent contamination.

As Clorox settled around unseen, unproven germs in the well, the purebred water taste dissipated. On my last visit to my parents’ home, I used, with some hesitation, a faucet filter, as I filled up a glass. The water tasted okay. Still disbelieving that our well water was changed, I dumped out the glass, switched off the filter, and filled up another glass. I held the water up to my nose. I could smell the bleach.

The well repair workers assured my mother and father that the chemical taste would go away in two weeks. Almost four weeks have passed since the repair.

The whole experience was a reminder: Do not take for granted the access to clean water.

Must start somewhere, starting here

Last month a bunch of scientists, the best and the brightest, flew, drove, or took the train to Yale University for ScienceWriters2010 sponsored by the National Association of Science Writers (NASW). For any writer with an insatiable interest in the sciences, this is a spiffy event. A person practically trips over the news story possibilities. This meeting in New Haven marked my second journey, a pilgrimage, really, to be with writers and storytellers of all backgrounds bound by a common interest: science is fun.

I wanted to rush home and write, write, write! I sorely missed the thrill of writing for daily newspapers, where I’d earned a living before returning to the University of Georgia for graduate degrees in conservation ecology and health & medical journalism.  Sure, the writing would be fun. But who would read what I wrote? How?

Start a blog, everyone said. Such advice fell on skeptic ears. Sure, I knew about blogs and I had even started one a while back for a class project. But for a blog to be successful, I thought the blogger needed to be mostly famous or part of a larger publishing group. Then I began to have conversations with other bloggers, in particular the writers of A Blog Around the Clock (thanks for the encouragement, Bora!), Superbug on Wired and Speakeasy Science, all of whom had humble beginnings, but who now reach thousands and more readers each day.

So here’s my voice. Here’s my humble blog beginning. Thank you for reading.