Monthly Archives: November 2012

Mysterious new SARS-like coronavirus came from bats

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Genetic analysis has confirmed that the cases of SARS-like viral disease that made headlines this fall—first killing a Saudi Arabian man in June and then sickening a Qatari man in September—were the result of a single coronavirus strain that made the leap from bats to humans.

“These two individuals were exposed to the same virus that was harbored in bats in the Saudi Arabian peninsula,” says Ralph Baric, a microbiologist at University of North Carolina–Chapel Hill who was not involved in the work.

A team led by Ron Fouchier, a virologist at the Erasmus Medical Center in the Netherlands, sequenced all 30,000 nucleotides of the new virus’ genome. Reporting today in mBio, the researchers found that the virus is most closely related to two coronaviruses found in bats, one from vesper bats and another from pipstrelle bats. The finding mirrors earlier discoveries that bats often serve as reservoirs and likely sources of coronaviruses for people. It also validates preliminary molecular details reported earlier this month in the New England Journal of Medicine.

In unpublished material disclosed in a press release to accompany the mBio paper, Fouchier and his colleagues additionally found that the isolates from the first two men infected with the virus differed by only 99 nucleotides, indicating that the two viruses are the same species. Genetic data from a third viral isolate taken from another Saudi Arabian man who earlier this month came down with what scientists think is the same coronavirus  are not yet available.

It could be worse

Although it’s still too early to make definitive statements, Baric says that the novel coronavirus—dubbed HCoV EMC/2012—does not appear to be transmissible between people, which distinguishes it from the virus responsible for severe acute respiratory syndrome (SARS) that spread between thousands of people a decade ago, killing around 10% of those infected. “If it were as transmissible as SARS, it would be much more dangerous,” he says.

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Computer program aims to rank vaccine development decisions

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WASHINGTON, DC — Aligning the priorities of all stakeholders involved in vaccine development can be a convoluted and thorny process. An international health organization might emphasize a candidate vaccine’s expected health benefits for disadvantaged populations, a government agency might be more focused on its own backyard, and a drug company could be driven by its monetary bottom line. With so many competing interests, what experimental product does it make the most sense for these partners to pursue?

Soon, a mathematical model that’s particularly good at weighing complex alternatives may be able to help. It’s at the heart of a new computer program, called the Strategic Multi-Attribute Ranking Tool (SMART) for Vaccines, that scores potential avenues for vaccine research and development according to the priorities fed into its algorithm. Members of the US Institute of Medicine (IOM) panel behind the new tool, who discussed the algorithm’s prototype at a meeting here on 2 November, hope it will establish a shared vocabulary that will allow everyone working on preventative vaccines for infectious agents to better understand and share their own perspective. “We’re creating a common language for people to talk with, instead of everyone having their own language,” says IOM committee member Charles Phelps, a health economist at the University of Rochester in New York.

In the past, the IOM simply released reports that encouraged vaccine developers to prioritize tackling certain diseases on the basis of the balance of expected health benefits, the costs of developing and administering the vaccine and the projected savings from the preventative medicine. For instance, in the most recent report, published in 2000, the IOM strongly favored targeting influenza, a virus that kills up to 49,000 people each year in the US at a cost of tens of billions of dollars annually to the country’s economy. In contrast, the bacteria responsible for Lyme disease, a far less prevalent pathogen with a smaller economic burden, fell much lower on the priority list.

The IOM had intended for vaccine developers to take its rankings into account when making decisions. However, according to Paul Offit, chief of infectious diseases at the Children’s Hospital of Philadelphia and a co-inventor of the rotavirus vaccine, such lists tended to justify choices that had already been made. “When the IOM puts a list out,” he says, “[vaccine manufacturers] feel that validates what they’ve done.”

With the SMART tool, any organization can generate its own priority rankings, custom-tailored from a list of 29 different vaccine attributes, including the number of premature deaths expected to be prevented from immunization, the availability of other medical interventions and whether the targeted disease has been stigmatized. A vaccine maker could give more weight to economic considerations such as the costs of clinical trials and licenses, say, whereas a defense-related agency could flag diseases that tend to afflict military personnel serving abroad. Out pops a numerical score for each candidate under consideration, thanks to a computational method also used to weigh complicated options for expanding Mexico City’s airport decades ago. Each score is broken down to reveal how much the chosen priorities contributed to the final number.

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Malaria vaccine results present infant immunization quandary

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Babies receive a battery of vaccines after they’re born to protect them against dreaded diseases such as tetanus, whooping cough and polio. Public health officials in the developing world had hoped to soon add a malaria (Plasmodium falciparum) vaccine to the childhood immunization schedule to take advantage of the existing vaccine distribution system. However, new results from a trial of the leading candidate—a shot known as RTS,S, or Mosquirix—suggest that the vaccine reduces the risk of malaria by only a third in infants.

Given the low efficacy, some experts are now questioning whether RTS,S would be a useful addition to the childhood vaccination roster. John Lusingu, a malaria researcher at the National Institute for Medical Research in Tanga, Tanzania, and a principal investigator on the trial, points out that children six months and older are most affected by the disease, so it might make sense to administer the vaccine to older children, for whom the vaccine is more protective. But that would probably require an expansion of the routine immunization program to include additional clinic visits, which can be burdensome for health workers and families.

The vaccine’s developers, GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative, plan to push on with the phase 3 trial, which is slated to end in 2014. “This is not a mission we should just walk away from,” Andrew Witty, chief executive of GSK, said in a press conference on 9 November. The London-based company has spent approximately $300 million on RTS,S to date and expects to invest another $200 million before the project is finished.

The study, published last week in the New England Journal of Medicine, included more than 6,500 infants between 6 and 12 weeks old from across seven African countries. The vaccine reduced the risk of clinical episodes of malaria by 31% in this young cohort, a lower level than that found in children vaccinated between 5 and 17 months for whom the vaccine provided up to 56% protection.

Why the vaccine is less effective in infants than it is in toddlers isn’t yet clear, but the research team behind the trial has a number of hypotheses. One complicating factor could be antibodies passed on from the babies’ mothers during pregnancy. These maternal antibodies protect infants from disease, but they can also prevent vaccines from eliciting a strong immune response .

Those same antibodies decay over time, though, so the older group of children would probably have had lower levels of them, says Rick Fairhurst, chief of the malaria pathogenesis and human immunity unit at the US National Institute of Allergy and Infectious Diseases in Rockville, Maryland. The effect could be especially pronounced in areas with the highest burden of malaria. Repeated exposure to the parasite results in higher levels of antibodies in the mothers, which can then be passed on to the children.

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Select agent status could slow development of anti-SARS therapies

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Saudi Arabian doctors scrambled last month to treat a third person who had fallen ill from a new strain of coronavirus that emerged earlier this year in the Middle East. The man survived with the help of supportive care from his physicians, but one of the other two patients who fell victim to the mysterious virus—a pathogen that resembles the coronavirus responsible for severe acute respiratory syndrome (SARS)—was not so fortunate.

{credit}CDC{/credit}

These recent cases drive home an all too stark reality: a decade on from the SARS outbreak that killed close to 800 people worldwide, scientists still have no proven effective vaccines or drugs that can stop the spread of SARS or SARS-like viruses, let alone mitigate their symptoms. Now, to make matters worse in the face of an emerging threat, a new reclassification of the bioterrorism risk posed by SARS may hamper efforts at novel medical strategies.

“Many labs are going to destroy their [SARS] virus instead of continue to work on it because the burden of regulation is quite high,” says Rachel Roper, a microbiologist at East Carolina University Brody School of Medicine in Greenville, North Carolina.

Roper has worked with SARS since the global pandemic ten years ago. She led the team that sequenced the virus’s genome, and, more recently, she and her colleagues created two experimental vaccines: a whole, killed SARS virus shot and an adenovirus-based vector carrying key SARS structural proteins. Both products elicited some degree of immune response and partially prevented viral replication in mice and ferrets. However, the protection was incomplete.

She had been working to improve both strategies and was already struggling with how she would advance a lead candidate into the clinic in the absence of any natural human SARS challenge against which to test it. Then, on 5 October, the US government announced plans to add SARS to its list of select agents. This reclassification, which goes into effect on 4 December, requires labs to now obtain additional licenses and adhere to stricter levels of biosafety and biosecurity to conduct any experiments with the virus. Although Roper recognizes that the move was made in the interest of protecting public health, for her this was the last straw. She says she no longer plans to work on SARS, opting to destroy her live virus instead of seeking certification for her lab.

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Grant winner decided by ‘American Idol’-style public vote

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BOSTON — With so many topnotch research proposals seeking funding but only limited grant money to go around, deciding which among the best of the best projects to support is no easy task. What if you have a number of equally commendable applications and you don’t know how to break the tie? Usually, a panel of experts will weigh the merits of the various projects and come to some consensus behind closed doors. But in an unconventional twist, the Brigham and Women’s Hospital (BWH) has opted to let the general public act as scientific judge and jury.

After six weeks of online voting and nearly 6,500 votes cast, the decision was in. Today, the Harvard-affiliated hospital announced that a project designed to explore how best to integrate genomic sequencing into routine medical care for healthy newborns had won the inaugural BRIght Futures Prize. The project’s leader, clinical geneticist Robert Green, and his team received a $100,000 research grant from the BWH’s Biomedical Research Institute (BRI).

“I’m not sure if there’s any other example where an academic institution has allowed the public to decide to whom they’ll give some of their hard-earned, hard-raised research money,” says Jacqueline Slavik, executive director of the BRI.

“Our goal was really to engage the Brigham community at large,” adds Lesley Solomon, director of strategy and innovation at the institute. “We want the world to know about the breadth and depth of the research that goes on here.”

It may sound akin to a popularity contest, but Slavik and Solomon are quick to point out that all three finalists for the prize had gone through a rigorous, behind-the-scenes, peer-reviewed vetting process before reaching the final stage. Review committees with expertise in personalized medicine and systems immunology—the two subject areas for which the BRI solicited proposals for the prize—winnowed the list of applicants down to a series of semifinalists. Each selected applicant made an in-person pitch to the BRI’s Research Oversight Committee, which ultimately chose the three proposals that were presented to the public. The three finalists then worked together with the hospital’s public affairs team to create a series of videos and brief nontechnical descriptions about the projects that were hosted on the voting site.

“It’s a new way of trying to decide who gets the money when you have equally meritorious projects,” says Slavik. “We could flip a coin,” she quips. Instead, by engaging the public, “we achieve several goals at once,” without sacrificing scientific rigor.

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Brigham and Women’s obtains ‘clarity’

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It’s got to be quite a competition when the winner can boast solving a family’s medical mystery, but those are the bragging rights the clinical genetics division at Brigham and Women’s Hospital captured when it won Boston Children’s Hospital’s first CLARITY contest (short for Children’s Leadership Award for the Reliable Interpretation and appropriate Transmission of Your genomic information).

In January, the Children’s Hospital put out the call for submissions, asking participants to help determine the unknown genetic root cause of illness in three children. The teams could sequence the genomes of the children and their parents, and were tasked with interpreting the information. The ultimate aim of the competition was to shed light on how data from whole genome sequences can be made most useful in a clinical setting (see ‘Genomics contest underscores challenges of personalized medicine‘).

There was a “real question of whether these technologies are ready for prime-time clinical applications,” says Isaac Kohane, an endocrinologist at Children’s Hospital. “What these teams have demonstrated is that going from end to end—from a genome sequence to a clinical readable report—can be turned into a routine process.”

Of the 23 teams submitting entries, three were able to identify both mutations in the titin and GJB2 genes that, respectively, explained the muscle weakness and hearing impairment afflicting one of the youngsters, a sixth grader. The Brigham and Women’s team provided the most insight on these points, winning the $15,000 top prize. Meanwhile, a team from University of Iowa in Iowa City was awarded $5,000 as a finalist for their approach to communicating unexpected genetic results, which they based on patient preferences. A German team (with representatives from the gene sequencing companies Genomatix and CeGaT, as well as the Institute of Pathology at the University of Bonn) also received $5,000 as a finalist for flagging all likely genetic mutations in the three cases.

The Children’s Hospital team behind the contest plans to publish a paper comparing and contrasting the various approaches taken by the entrants in the contest, according to Kohane. The hope is that this information from the contest will help inform procedures in the gene sequencing field. They’re also planning a second challenge, focused on cancer genomes, to carry on their efforts of helping understand how to process the large data sets and communicate the information to patients.

Image courtesy of Shutterstock

Insurance challenges may lie ahead for New York labs hit by hurricane

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At the end of turbulent week, the extent of the damage caused by Hurricane Sandy on biomedical research in the Northeast remains unclear, particularly at New York University’s Smilow Research Center, which flooded during the storm. The most devastating loss at the labs there may be the death of thousands of genetically modified mice and rats, and these animals represent the culmination of many years of research and thousands of dollars in funding. Although the cages the rodents lived in may be insured, it’s likely impossible to recoup the money and time spent to engineer the animals themselves. Biomedical scientists may not think about the insurance needs for their labs on a daily basis, and as some Nature Medicine spoke with, it’s not always easy to get experiments up and running even when insurance is in place.

The accident in May at the McLean Hospital in Belmont, Massachusetts, may provide a glimpse of the challenges ahead for local labs. Around 50 brains from individuals with autism were ruined when the freezer they were stored in malfunctioned, warming up without setting off any of the in-place indicators. The hospital will likely receive reimbursement for the failing freezer, and compensation for new freezers the hospital has had to rent in the interim, but there will likely be no reimbursement for the brains themselves, says Peter Paskevich, senior vice president of research administration at McLean. Money can’t buy back what they lost, Paskevich adds: “We could get half a million dollars for the autism collection but it doesn’t matter — it’s still going to take 20 years to replace it.” McLean is currently negotiating with a private insurance company that will cover the accident, though the dollar amount has not been decided.

Other universities are primarily self-insured, meaning the university compensate for such disasters with their own funds that they set aside earlier, says George Stancel, executive vice president for academic and research affairs at the University of Texas Health Science Center in Houston. UTHealth experienced flooding and damage after Hurricane Allison in 2008, and relied on primarily on its self-insurance, though its buildings were insured through a separate insurer. The Federal Emergency Management Agency (FEMA) also helped with repairs and rebuilding labs, Stancel says.

Similarly, when the University of Iowa, in Iowa City, experienced severe flooding in 2008, it also relied on help from FEMA as it rebuilt, as it was primarily self-insured, says Mark Arnold, a chemist at the university.

It’s currently unclear what type of insurance policy NYU will rely on as it begins to rebuild; it is busy coping with the damage and has yet to respond to requests for comment from Nature Medicine. But in the meantime researchers at other intuitions who have endured damage from other natural disasters offer the following advice on how to start rebuilding to scientists affected by the storm this week:

  • Take inventory. In sorting through all equipment, take detailed notes of what has been damaged and what may have been damaged. FEMA and most insurance companies require detailed inventory lists for reimbursement, Stancel says, and Arnold warns that even if something seems to be working right now, it may still have suffered damage, so noting its exposure now is critical for reimbursement.
  • Keep track of time. As researchers, graduate students and laboratory assistants are reentering labs and attempting to move precious items to safer locations, keeping track of time may mean that the insurance company could reimburse these hours down the road.
  • Call the program officers who are responsible for labs’ funding to see if there is any option for extending research deadlines or securing supplemental research funding. The NIH extended deadlines for researchers at UTHealth following Hurricane Allison, Stancel says.
  • Help graduate students get on a fast track. Losing research is most devastating for graduate and PhD students who are attempting to complete research in a set period of time. Stancel, who was dean of the graduate school when Hurricane Allison hit, says he immediately asked graduate students to start rethinking their projects. Having them work at and with other laboratories helped alleviate the time crunch, he says.
  • Consider how buildings may be rebuilt and redesigned so this doesn’t happen again. While the desire to get labs rebuilt will be immediate, taking some time to decide what the best path forward for prevention of a reoccurrence of the situation is worthwhile. For example, Stancel moved all of the animal laboratories from the basement to the fifth and sixth floors to prevent animals from drowning in future floods.
  • While most insurance policies don’t have a way to reimburse researchers for their lab animals, which hold so much work, collaborating with other researchers who have done similar work may help to quickly rebuild at least parts of the populations that were lost. Yariv Houvras, who studies zebra fish at Cornell Weill Medical School in New York City says that because he’s distributed lines of his fish to other researchers, he could get similar lines back in the case of a disaster. Researchers at the University of Pennsylvania in Philadelphia, and Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, have already made offers, according to The New York Times.
  • Raise money for research. While funding agency want to help researchers, Arnold says the University of Iowa received limited extra funding after their flood disaster, because research funding is so tight. In the case of Hurricane Sandy, it may be possible to set up a relief fund, as New York and the surrounding area are receiving “national and international attention.”

Got extra tips? Leave them in the comments section, or tweet at us — @NatureMedicine.

Image: NOAA

Global vaccination coverage improves, but rotavirus gap is wide

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Over the past year, Rwanda, Ghana, Malawi and Yemen have all joined the growing list of developing countries that have introduced vaccines against rotavirus as part of their standard national immunization programs. Yet the vast majority of the world’s children still remain at risk of infection by this vaccine-preventable pathogen, which can cause fatal gastrointestinal disease. And the situation isn’t much better for several respiratory diseases, either.

According to the latest global survey of routine vaccine coverage, tens of millions of children last year missed out on some or all of the basic recommended immunizations.

The rotavirus vaccine as well as the pneumococcal conjugate vaccine, which protects against Streptococcus pneumoniae, were administered to less than 15% of all kids outside the Americas and Europe, the report found. Similarly, global coverage of the Haemophilus influenzae type b vaccine, which protects against a bacterium responsible for bacteremia and pneumonia, among other diseases, was only 43% last year among youngsters, despite the shot being recommended in routine childhood vaccination schedules in more than 90% of the world’s nations.

The findings (see chart) were reported today jointly by the World Health Organization (WHO), the US Centers for Disease Control and Prevention and the United Nation’s Children Fund.

There is reason for optimism, though. More than four in five children worldwide now routinely receive the four lifesaving vaccines that the WHO began recommending in 1974. These include the diphtheria-tetanus-pertussis (DTP), bacille Calmette-Guérin, oral poliovirus and attenuated measles vaccines. By comparison, forty years ago less than 5% of all children received a full dose of the DTP vaccine, for example.

“The report offers us gold medals in some places and offers us challenges in others,” says William Schaffner, a vaccine specialist at Vanderbilt University School of Medicine in Nashville, Tennessee.

Efforts are now in place to boost all these numbers. Earlier this year, the WHO’s World Health Assembly adopted a global vaccine action plan that outlines plans to meet certain immunization target levels in every region, country and community in the world by the end of the decade.