Monthly Archives: January 2012

Are chimpanzee viruses the answer to a vaccine conundrum?

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For years, researchers have tinkered with adenoviruses, which can cause illnesses such as the common cold, using disabled versions of the pathogens to build vehicles for vaccine delivery. And now there’s a new spin from a different species. This week, scientists reported that chimpanzee adenoviruses could be used as the backbone for a vaccine against hepatitis C virus (HCV); the findings, published in Science Translational Medicine, were met with an enthusiastic response. Two teams published back-to-back work; the first group isolated more than two dozen chimp adenoviruses from thousands of the animals’ stool samples and identified the one that induced the biggest response in two types of T-cells in the immune systems of mice and non-human primates, making it a potential tool for vaccination against HCV. The second tested that viral vector in a phase 1 clinical trial and saw that healthy people showed an immune response comparable to that produced by a human adenoviral vector vaccine.

Paul Klenerman, an immunologist at Oxford University in the UK, was a member of the second group and says the team was excited to see an increased immune response from two classes of T-cells “that was at least as strong as what we see in people who clear HCV naturally.”

Virologists have proposed potential chimp adenovirus vaccines for everything from malaria to HIV to cancer. Klenerman says they offer an excellent alternative to human adenoviruses, to which we may have pre-existing immunity that could potentially disable the vaccines based on them. He’s not the only one to raise that possibility—ever since the still-unsolved failure of the STEP HIV vaccine trial, which tested a human adenovirus-based HIV vaccine, immunologists have puzzled over pre-existing immunity.

But is it time to go bananas over chimp adenoviruses? The bigger picture is that immunologists are not in lockstep when it comes to the effects of pre-existing immunity on adenovirus-based vaccines. Michael Betts, an immunologist at the University of Pennsylvania in Philadelphia, was one of the authors of one of two studies published in Nature Medicine in 2009 that provided evidence against pre-existing immunity as the cause of the STEP trial meltdown. He says that ultimately the question of viral immunity in vaccines is still a black box: “Without knowing more about immunity, it’s hard to say that chimp adenoviruses are likely to be any better than any other adenoviruses.” And although the preliminary results published this week are positive, they are far from conclusive; a second trial to test the protective ability of the vaccine is currently underway. With some luck, this field of research should shed light on whether chimp vectors mean more than just swinging from the trees.

Image by Steve Snodgrass via Wiki Creative Commons

Chimeric monkeys provide new disease model

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Chimeric mice are one of the most important tools in biological research. By studying composite animals with tissues from distinct genetic lineages, scientists have gained important insights into the molecular mechanisms of disease. This powerful biomedical research tool has largely been restricted to rodents and farm animals that are distantly related from humans, and, thus, might not best approximate human disease. Now, however, rhesus monkeys have joined the chimera club—an advance that researchers hope will help bridge the gap between mice and humans.

“It is not enough to jump from mouse right to human in transplanting tissues,” says Shoukhrat Mitalipov, a developmental biologist at the Oregon National Primate Research Center in Beaverton who led the study. “We need primate models to know if tissues are truly functional.”

In their study, Mitalipov and his colleagues plucked cells from early-stage monkey embryos containing only four cells each. They then mixed the cells together into aggregates containing cells from between three and six different embryos. After growing the cells up to the blastocyst stage, they implanted 14 of the cell clusters into five females. The scientists terminated three of the pregnancies for genetic analysis, but the other two monkeys gave birth to healthy baby boys: a pair of twins named Roku and Hex (pictured here), and a singleton name Chimero. These monkeys were indeed chimeric—with some cells originating from female embryos, too—as the researchers detected multiple genotypes in the animals’ blood cells. The findings were published today in Cell.

This method stands is in stark contrast to that typically used to create chimeric rodents. In mice and rats, scientists usually inject cultured embryonic stem cells into developing embryos from another animal strain. Although Mitalipov has cloned monkey embryos in the past, and even derived embryonic stem cells, his attempts to create chimeric monkey fetuses using cultured embryonic stem cells failed repeatedly because the stem cells didn’t incorporate properly into the host embryo.

Rhesus monkeys are currently used for a host of different biomedical applications, including studies of HIV and influenza viruses. For such studies, especially those on drug therapies, which often now go directly from mouse to human testing, the addition of a chimeric monkey model will be a crucial bridge for vetting the potential translation of findings to humans.

Image courtesy of Oregon Health & Science University

TPTB unveil ‘JDRF’, symptomatic of an acronym epidemic IMHO

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In a sign of the times, the TPTB at the Juvenile Diabetes Research Foundation today that the organization is abandoning its name and simply adopting the initials JDRF.

True to type—type 1 diabetes, that is—the 41-year-old, New York-based non-profit unveiled its new name, logo and tagline that it says “better reflects the state of type 1 diabetes (T1D) and the organization’s work, which remains committed to curing, treating, and preventing the disease.”

It’s juvenile of me to quibble really about the loss of the old moniker. True, the disease is now known as T1D, not juvenile diabetes. And yes, the disease affects adults just as much as, if not more than, kids. OTOH, if it’s truly no longer a juvenile disease, then why keep the ‘J’ in JDRF? IMHO, the organization should consider changing the name to Type 1 Diabetes Research Foundation. People are savvy enough to learn to use the shorthand T1DRF.

BGI. GAVI. BMJ. PATH. All these biomedically-relevant acronyms used to stand for something. Now, they are just letters evoking a bygone era.

Most people don’t bother spelling out acquired immune deficiency syndrome. But no one refers to AIDS as GRID anymore as scientists now realize that the disease isn’t in fact caused by ‘gay-related immune deficiency’. Similarly, HIV is not called LAV or HTLV-III, as the virus once was once known.

The acronym epidemic has spread too far in biomedicine, from nonprofits to the names of clinical trials themselves (remember the TORPEDO trial?). The cure, BTW, is just a couple of extra keystrokes away.

Israeli drug giant announces new CEO

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Teva Pharmaceuticals is ascending rapidly. According to a recent report from Evaluate Pharma, a London-based research firm, the Israeli drugmaker is set to break into the top ten list of the world’s top-grossing pharmaceutical companies this year, and will maintain stronger growth than any other firms in the exclusive pharma club. But the man who took the company there and oversaw a doubling in Teva’s revenues over the past five years will not be the one guiding that expansion. On Sunday, Teva announced that chief executive Shlomo Yanai is leaving the company in May and will be succeeded by Bristol-Myers Squibb (BMS) executive Jeremy Levin.

Teva’s choice to appoint Levin is seen as a sign that the world’s largest generic drug manufacturer is looking to further broaden its market influence. In his five years at the helm, Yanai helped Teva expand its pipeline and diversify its assets, including the acquisition of Pennsylvania’s Cephalon earlier this year.

“The proprietary side of our business will change from a solo act…to a symphony in which we will be marketing a number of our own drugs,” Yanai told Nature Medicine in a Q&A last year.

Levin was, until Sunday, a senior executive at BMS, where he was responsible for acquiring promising biotechs as part of the New York-based company’s ‘string of pearls’ strategy to maintain a lucrative product pipeline.  He is widely expected to continue in this direction in his new position. “His appointment clearly signals that Teva will remain acquisitive in building its brand business,” Barclays Capital wrote in an investor note quoted by Globes.

Yanai’s departure notice comes just ten days after Teva announced that Rob Koremans, a Sanofi executive in charge of generic drug development, will head up Teva’s European operation, beginning in March.

Image: Wiki Creative Commons