NEWS OF THE W EEK
COMPANIES MEET VACCINE NEEDS PHARMACEUTICALS: Yellow fever
outbreak and neglected diseases spur corporate vaccine efforts
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NEWSCOM
Vaccinations are critical to halting the spread of yellow fever.
SOUTH AMERICAN OUTBREAK of more than 100 suspected cases of yellow fever has mobilized global health groups and their drug industry partners to supply needed vaccines. There is no treatment for the viral disease, only prevention via immunization. Thus, vaccinations must be given quickly after an outbreak to keep yellow fever from spreading, particularly in populated areas. Early last week, the United Nations Children’s Fund (UNICEF) delivered to Paraguay 2 million doses of vaccine supplied by Sanofi Pasteur, the vaccines division of France’s Sanofi-Aventis. The drug company is a leading manufacturer of yellow fever vaccine and supplies an emergency stockpile managed by an international group that includes UNICEF. Previously, Brazil and other countries in the region provided some of the needed vaccine. Brazilian officials, however, sus-
VIRUS CAPSID REVEALS SURPRISES STRUCTURAL BIOLOGY: Improved
resolution uncovers a second protein in outer protein shell
N ATUR E © 2008
Two different proteins make up the capsid of the ε15 phage.
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TEAM OF RESEARCHERS has pushed the
resolution of single-particle electron cryomicroscopy (cryo-EM) to levels that allow them to trace the backbone of the 22-megadalton capsid, or outer protein shell, of the ε15 bacteriophage, a virus that infects the bacterium Salmonella anatum (Nature 2008, 451, 1130). The improved resolution is “a quite significant achievement,” says James Conway, cryo-EM group leader in the department of structural biology at the University of Pittsburgh School of Medicine, who was not involved with the research. “This is a 20-plus-megadalton assembly. With this structure, Wah Chiu’s group and others are showing that atomic resoluWWW.C E N- ONLI NE .ORG
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pended exports of yellow fever vaccine after an outbreak in their country, according to the World Health Organization. At the request of health authorities, Sanofi Pasteur supplied 4 million doses of its yellow fever vaccine to Brazil in early February. The vaccine stockpile now contains only 6 million doses, WHO says, but an additional 18 million should come from manufacturers by the end of April. Meanwhile, the Swiss firm Novartis has opened the Novartis Vaccines Institute for Global Health (NVGH) in Siena, Italy. It is Novartis’ second institute focused on neglected diseases of the developing world—the company set up the Novartis Institute for Tropical Diseases in Singapore in 2002—and the first by a major vaccine developer. Allan Saul, formerly with NIH’s National Institute of Allergy & Infectious Diseases, will head the nonprofit institute. The institute will focus its initial efforts on diarrheal diseases arising from Salmonella typhi, Salmonella paratyphi A, and nontyphoidal salmonellae (NTS) bacteria, which cause infection and disease in children. Multi-drug-resistant NTS is a leading cause of death for African children under five. The institute’s goals are to bridge the gap between basic research and product development and to leverage public-private partnerships. Vaccines discovered by NVGH will first be introduced in developing countries. “Accessibility to and affordability of NVGH products will be the priority, not commercial value or profit potential,” says Paul Herrling, head of corporate research at Novartis.—ANN THAYER
tion is not an unreasonable expectation in the not-toodistant future.” The 4.5-Å resolution allows the team, led by Baylor College of Medicine’s Chiu, to trace the backbone of the major capsid constituent, a protein called gp7. In doing so, they discovered that the capsid actually contains two kinds of proteins, rather than one, as originally thought. “If the map was low resolution, we might have thought this was one continuous protein,” Chiu says. But the structure was clear enough to indicate that a second protein was present. The team confirmed its structural findings with biochemical and proteomics analyses. The second protein turns out to be a 12-kDa protein known as gp10, which probably serves as a “molecular staple” that increases the particle’s stability. To make the data analysis more computationally tractable, Chiu and coworkers imposed icosahedral symmetry on the entire particle. This icosahedral averaging method limits what they can see to those portions that follow icosahedral symmetry, Chiu says. For example, the portal, a protein structure at one vertex that lets viral DNA in and out of the capsid, can’t be visualized this way. The team is working on algorithms that don’t require icosahedral symmetry, but these require the collection of many more particle images.—CELIA ARNAUD
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