Meningitis Vaccine
Content
NEWS OF THE WEEK
VA C C I N E I N T R O D U C T I O N
The Beginning of the End for Africa’s Devastating Meningitis Outbreaks?
and other vaccines for poor countries. “I think it is one of our most important milestones of the decade. And I’m not the only one who thinks so,” Elias said in an interview from Abuja, Nigeria, en route to Burkina Faso to witness the symbolic first shot. Also there to celebrate were Blaise Compaoré, the president of Burkina Faso; Margaret Chan, director-general of the World Health Organization (WHO); Tachi Yamada, head of the Global Health Program at the Bill and Melinda Gates Foundation, who calls MenAfriVac an “amazing success”; and Helen Evans, interim CEO of the GAVI Alliance. And, of course, Marc LaForce, who shepherded the vaccine through its rocky birth and adolescence I CA as head of the Meningitis Vaccine Project, a collaboration of PATH Meningitis belt countries All-star cast. Burkina Faso’s and WHO that was first lady, Chantal Compaoré, launched with a large was one of the dignitaries at the grant from the Gates launch of a new meningitis vaccine, which promises to put an end to the deadly Foundation. “I’m pretty epidemics in Africa’s meningitis belt (above). excited,” says the 71-yearold LaForce, who says witnessing the launch was “humbling.” U n t i l n ow, there has been no way to prevent the deadly meningitis epidemics that erupt across a swath of sub-Saharan Africa (see map) each year with the onset of the dry season in January or February and tional standards and designed specifically for stop abruptly with the rains in May or June. Africa—and for a particularly African scourge, (Burkina Faso, Mali, and Niger, the three meningitis A. (Meningitis A is virtually non- countries where the vaccine is first being existent in Western countries.) What’s most launched, are particularly hard hit.) An infecremarkable, experts say, is its price, a mere tion of the thin membrane that lines the brain, 44 cents a dose, and the speed with which meningococcal meningitis can kill within it was developed and delivered—less than 24 hours and often leaves its survivors deaf 10 years from when the idea was hatched. or intellectually impaired. Several strains of “That quick an introduction hasn’t hap- Neisseria meningitides can cause meningitis, pened before,” says Chris Elias, president of but group A accounts for about 85% of epithe nonprofit PATH in Seattle, Washington, demic disease. which has played a key role in developing this An older polysaccharide vaccine was Nine years ago, a small group of infectiousdisease experts gambled on an unorthodox strategy to make a much-needed—and affordable—vaccine for Africa. Last Monday in Burkina Faso, it paid off in spades with the kickoff of a massive campaign to immunize 20 million people in three African countries against deadly meningococcal meningitis by the end of December. The eventual goal, if the money comes through, is to immunize some 250 million people in 25 countries over the next several years, putting an end to the ferocious epidemics that regularly sweep across Africa’s so-called meningitis belt (Science, 27 June 2008, p. 1710). MenAfriVac, as it is called, is the first new vaccine made AFR to the highest interna-
developed in the 1960s. But its effectiveness is so limited—immunity lasts for just 2 or 3 years, and it has minimal benefit in children under 2—that it is used only as a “Band-Aid” in reactive campaigns to limit the spread of epidemics that have already begun. The vaccine often arrives too late to do much good. The new conjugate vaccine uses the same polysaccharide from the bacterium’s coat but links, or conjugates, it to a protein that makes it far more immunogenic. LaForce thinks that MenAfriVac will protect for at least 10 years. And unlike the older vaccine, the conjugate prevents those infected from transmitting the bacteria, thus conferring “herd immunity,” or protecting those who don’t receive the vaccine. It is modeled on a far more expensive conjugate vaccine that has all but wiped out the related meningitis C in several European countries. When LaForce took on the job, he quickly realized that the accepted strategy— working with big pharma to adapt a vaccine, then negotiating to get the price down—would not deliver a vaccine that met his definition of “affordable.” A conjugate pneumococcal vaccine now poised for introduction in developing countries, for instance, costs roughly $3.50 a dose. Instead, LaForce insisted on a guaranteed selling price of less than 50 cents and set out to find partners who could make it happen. When big pharma did not step up, LaForce hatched a scheme to work with an Indian manufacturer, Serum Institute of India Limited, among others. Some of his partners in the project were skeptical, says LaForce. “We asked some tough questions,” recalls Elias. “Marc was convinced it was going to work. But he had to convince the global health community.” It was risky, he says, to “work with a company that did not have a major research focus like big pharma and that hadn’t worked with a conjugate vaccine before, in a country that had never regulated a conjugate vaccine before.” Now Elias calls MenAfriVac a model for delivering all sorts of public health interventions, not just vaccines, to poor countries. So does Yamada, who says the Gates Foundation is investing in a new pneumococcal vaccine that is being developed at Serum in India as well. “We have high hopes it will come in well under $3.50,” says Yamada. But despite all the fanfare surrounding last week’s launch, LaForce notes that MenAfriVac’s widespread introduction is by no means assured. In 2008, GAVI approved the $370 million plan for the full vaccine rollout, but, in an unexpected move, the financially strapped organization provided limited funding—$29.5 million—for intro-
1466
10 DECEMBER 2010
VOL 330
SCIENCE
www.sciencemag.org
Published by AAAS
CREDIT: PATH
Downloaded from www.sciencemag.org on December 10, 2010
NEWS OF THE WEEK
duction in just the first three countries, as well as $55 million to stockpile the old vaccine for emergencies until the new one is widely available. “It’s an ongoing challenge, what will GAVI do for the next countries,” says LaForce, who says he won’t breathe easily until the money is in the bank. Helen Evans of GAVI says the organization, facing a roughly $4 billion funding gap over the next 5 years, is committed “in principle” to providing the full $370 million by 2015—if GAVI’s donors step up. Otherwise, “choices will have to be made about which vaccines to prioritize,” adds a spokesperson. The vaccine must still prove its mettle in the follow-on studies that are already beginning. A key issue is serotype shifting. The worst case, which LaForce considers unlikely, is that the vaccine will prove effective against type A, but then another strain would move in to fill that niche. That’s why work is already beginning on a multivalent vaccine, says Elias, but it will be harder to make and will undoubtedly cost more. In the best case, Elias says, if the meningitis A vaccine works as expected, those districts that were immunized in December will be spared this season’s epidemic. “We should know by June,” Elias says.
–LESLIE ROBERTS
ScienceNOW
From Science’s Online Daily News Site
Why Diets Fail Bad news for dieters: New research shows that dieting makes the brain more sensitive to stress and the rewards of high-fat, high-calorie treats. And that can cause you to regain lost weight. Stress triggers the release of cortisol, a “fight or flight” hormone that, if chronically elevated, can cause increased appetite and weight gain. Tracy Bale, a neuroscientist at the University of Pennsylvania, and colleagues hypothesized that dieting leaves people more susceptible to the stresses of everyday life, leading them to pack on lost pounds. To test the idea, the team put lab mice on a 3-week diet until the rodents had lost about 10% to 15% of their original body weight. After exposure to mild forms of stress, the mice’s blood cortisol levels shot up higher and stayed elevated longer compared with levels in control mice. But even after a week of normal eating, the ex-dieters remained more sensitive to stress and were more likely to eat large amounts of high-fat mouse chow when under pressure, the team reports in The Journal of Neuroscience. The team also found that the diet, although short, resulted in longterm changes in gene expression that would undermine any dieter’s efforts. The mice that dieted had significantly higher levels of the protein that stimulates cortisol release, indicating higher sensitivity to stress, as well as higher levels of appetite-stimulating hormones after exposure to the high-fat binge food. This may help explain why so many diets fail: Dieting increases stress sensitivity, and stress makes us seek relief in high-fat, high-calorie “comfort” foods. http://scim.ag/diet-fail How Swine Flu Killed the Healthy One of the most baffling questions of the 2009 H1N1 “swine flu” pandemic was why the virus killed healthy individuals while sparing the very young and the very old. The answer may be an immune system gone haywire, according to new research. Fernando Polack of Vanderbilt University in Nashville and his colleagues found that lung samples from 75 young and middle-aged adult victims of the 2009 pandemic contained a surprising amount of a protein called C4d. C4d usually binds to antibodies to form virus-fighting immune complexes. But in this case, he says, C4d probably did more harm than The lungs of this adult H1N1 good. That’s because the adult victim contain C4d (orange). antibodies—trained to fight sea-
Pollutant Changes Sexual Preference
A new study shows that mercury in the environment can change an animal’s mating habits. Peter Frederick of the University of Florida, Gainesville, and Nilmini Jayasena of the University of Peradeniya in Sri Lanka raised 120 wild white ibis chicks for 3 years, lacing some of the birds’ diets with mercury. The team reports in The Proceedings of the Royal Society B that 55% of male birds in the group exposed to the highest level of mercury, 0.3 parts per million, formed mating pairs with other males. Malemale pairs can occur in the wild when females are unavailable, but these birds had an ample supply of mates. Although the mechanism is unknown, the study suggests that mercury, a common pollutant from coal-burning power plants, may threaten the survival of ibises and other species, as no laws exist to protect them from exposure. http://scim.ag/mercury-changes
sonal flu—were a poor match for H1N1. They recognized the virus and latched on to it but weren’t able to stop it from replicating, says Polack. Unable to fight back, the system spiraled out of control, Polack speculates. Instead of punching holes in the viruses, the C4d-antibody complexes punctured the victims’ veins, flooding their lungs with water and plasma, the team reports in Nature Medicine. It makes sense that the old and the young didn’t have this strange reaction, Polack says. Young children and infants have few or no antibodies against seasonal flu strains, whereas elderly people had antibodies to an earlier H1N1 strain, known to be a much better match for the 2009 version. http://scim.ag/H1N1-victims Read the full postings, comments, and more at http://news.sciencemag. org/sciencenow.
CREDITS (TOP TO BOTTOM): JOSH WICKHAM/UF/IFAS; FERNANDO POLACK
www.sciencemag.org
SCIENCE
VOL 330
10 DECEMBER 2010
1467
Published by AAAS
Downloaded from www.sciencemag.org on December 10, 2010
VA C C I N E I N T R O D U C T I O N
The Beginning of the End for Africa’s Devastating Meningitis Outbreaks?
and other vaccines for poor countries. “I think it is one of our most important milestones of the decade. And I’m not the only one who thinks so,” Elias said in an interview from Abuja, Nigeria, en route to Burkina Faso to witness the symbolic first shot. Also there to celebrate were Blaise Compaoré, the president of Burkina Faso; Margaret Chan, director-general of the World Health Organization (WHO); Tachi Yamada, head of the Global Health Program at the Bill and Melinda Gates Foundation, who calls MenAfriVac an “amazing success”; and Helen Evans, interim CEO of the GAVI Alliance. And, of course, Marc LaForce, who shepherded the vaccine through its rocky birth and adolescence I CA as head of the Meningitis Vaccine Project, a collaboration of PATH Meningitis belt countries All-star cast. Burkina Faso’s and WHO that was first lady, Chantal Compaoré, launched with a large was one of the dignitaries at the grant from the Gates launch of a new meningitis vaccine, which promises to put an end to the deadly Foundation. “I’m pretty epidemics in Africa’s meningitis belt (above). excited,” says the 71-yearold LaForce, who says witnessing the launch was “humbling.” U n t i l n ow, there has been no way to prevent the deadly meningitis epidemics that erupt across a swath of sub-Saharan Africa (see map) each year with the onset of the dry season in January or February and tional standards and designed specifically for stop abruptly with the rains in May or June. Africa—and for a particularly African scourge, (Burkina Faso, Mali, and Niger, the three meningitis A. (Meningitis A is virtually non- countries where the vaccine is first being existent in Western countries.) What’s most launched, are particularly hard hit.) An infecremarkable, experts say, is its price, a mere tion of the thin membrane that lines the brain, 44 cents a dose, and the speed with which meningococcal meningitis can kill within it was developed and delivered—less than 24 hours and often leaves its survivors deaf 10 years from when the idea was hatched. or intellectually impaired. Several strains of “That quick an introduction hasn’t hap- Neisseria meningitides can cause meningitis, pened before,” says Chris Elias, president of but group A accounts for about 85% of epithe nonprofit PATH in Seattle, Washington, demic disease. which has played a key role in developing this An older polysaccharide vaccine was Nine years ago, a small group of infectiousdisease experts gambled on an unorthodox strategy to make a much-needed—and affordable—vaccine for Africa. Last Monday in Burkina Faso, it paid off in spades with the kickoff of a massive campaign to immunize 20 million people in three African countries against deadly meningococcal meningitis by the end of December. The eventual goal, if the money comes through, is to immunize some 250 million people in 25 countries over the next several years, putting an end to the ferocious epidemics that regularly sweep across Africa’s so-called meningitis belt (Science, 27 June 2008, p. 1710). MenAfriVac, as it is called, is the first new vaccine made AFR to the highest interna-
developed in the 1960s. But its effectiveness is so limited—immunity lasts for just 2 or 3 years, and it has minimal benefit in children under 2—that it is used only as a “Band-Aid” in reactive campaigns to limit the spread of epidemics that have already begun. The vaccine often arrives too late to do much good. The new conjugate vaccine uses the same polysaccharide from the bacterium’s coat but links, or conjugates, it to a protein that makes it far more immunogenic. LaForce thinks that MenAfriVac will protect for at least 10 years. And unlike the older vaccine, the conjugate prevents those infected from transmitting the bacteria, thus conferring “herd immunity,” or protecting those who don’t receive the vaccine. It is modeled on a far more expensive conjugate vaccine that has all but wiped out the related meningitis C in several European countries. When LaForce took on the job, he quickly realized that the accepted strategy— working with big pharma to adapt a vaccine, then negotiating to get the price down—would not deliver a vaccine that met his definition of “affordable.” A conjugate pneumococcal vaccine now poised for introduction in developing countries, for instance, costs roughly $3.50 a dose. Instead, LaForce insisted on a guaranteed selling price of less than 50 cents and set out to find partners who could make it happen. When big pharma did not step up, LaForce hatched a scheme to work with an Indian manufacturer, Serum Institute of India Limited, among others. Some of his partners in the project were skeptical, says LaForce. “We asked some tough questions,” recalls Elias. “Marc was convinced it was going to work. But he had to convince the global health community.” It was risky, he says, to “work with a company that did not have a major research focus like big pharma and that hadn’t worked with a conjugate vaccine before, in a country that had never regulated a conjugate vaccine before.” Now Elias calls MenAfriVac a model for delivering all sorts of public health interventions, not just vaccines, to poor countries. So does Yamada, who says the Gates Foundation is investing in a new pneumococcal vaccine that is being developed at Serum in India as well. “We have high hopes it will come in well under $3.50,” says Yamada. But despite all the fanfare surrounding last week’s launch, LaForce notes that MenAfriVac’s widespread introduction is by no means assured. In 2008, GAVI approved the $370 million plan for the full vaccine rollout, but, in an unexpected move, the financially strapped organization provided limited funding—$29.5 million—for intro-
1466
10 DECEMBER 2010
VOL 330
SCIENCE
www.sciencemag.org
Published by AAAS
CREDIT: PATH
Downloaded from www.sciencemag.org on December 10, 2010
NEWS OF THE WEEK
duction in just the first three countries, as well as $55 million to stockpile the old vaccine for emergencies until the new one is widely available. “It’s an ongoing challenge, what will GAVI do for the next countries,” says LaForce, who says he won’t breathe easily until the money is in the bank. Helen Evans of GAVI says the organization, facing a roughly $4 billion funding gap over the next 5 years, is committed “in principle” to providing the full $370 million by 2015—if GAVI’s donors step up. Otherwise, “choices will have to be made about which vaccines to prioritize,” adds a spokesperson. The vaccine must still prove its mettle in the follow-on studies that are already beginning. A key issue is serotype shifting. The worst case, which LaForce considers unlikely, is that the vaccine will prove effective against type A, but then another strain would move in to fill that niche. That’s why work is already beginning on a multivalent vaccine, says Elias, but it will be harder to make and will undoubtedly cost more. In the best case, Elias says, if the meningitis A vaccine works as expected, those districts that were immunized in December will be spared this season’s epidemic. “We should know by June,” Elias says.
–LESLIE ROBERTS
ScienceNOW
From Science’s Online Daily News Site
Why Diets Fail Bad news for dieters: New research shows that dieting makes the brain more sensitive to stress and the rewards of high-fat, high-calorie treats. And that can cause you to regain lost weight. Stress triggers the release of cortisol, a “fight or flight” hormone that, if chronically elevated, can cause increased appetite and weight gain. Tracy Bale, a neuroscientist at the University of Pennsylvania, and colleagues hypothesized that dieting leaves people more susceptible to the stresses of everyday life, leading them to pack on lost pounds. To test the idea, the team put lab mice on a 3-week diet until the rodents had lost about 10% to 15% of their original body weight. After exposure to mild forms of stress, the mice’s blood cortisol levels shot up higher and stayed elevated longer compared with levels in control mice. But even after a week of normal eating, the ex-dieters remained more sensitive to stress and were more likely to eat large amounts of high-fat mouse chow when under pressure, the team reports in The Journal of Neuroscience. The team also found that the diet, although short, resulted in longterm changes in gene expression that would undermine any dieter’s efforts. The mice that dieted had significantly higher levels of the protein that stimulates cortisol release, indicating higher sensitivity to stress, as well as higher levels of appetite-stimulating hormones after exposure to the high-fat binge food. This may help explain why so many diets fail: Dieting increases stress sensitivity, and stress makes us seek relief in high-fat, high-calorie “comfort” foods. http://scim.ag/diet-fail How Swine Flu Killed the Healthy One of the most baffling questions of the 2009 H1N1 “swine flu” pandemic was why the virus killed healthy individuals while sparing the very young and the very old. The answer may be an immune system gone haywire, according to new research. Fernando Polack of Vanderbilt University in Nashville and his colleagues found that lung samples from 75 young and middle-aged adult victims of the 2009 pandemic contained a surprising amount of a protein called C4d. C4d usually binds to antibodies to form virus-fighting immune complexes. But in this case, he says, C4d probably did more harm than The lungs of this adult H1N1 good. That’s because the adult victim contain C4d (orange). antibodies—trained to fight sea-
Pollutant Changes Sexual Preference
A new study shows that mercury in the environment can change an animal’s mating habits. Peter Frederick of the University of Florida, Gainesville, and Nilmini Jayasena of the University of Peradeniya in Sri Lanka raised 120 wild white ibis chicks for 3 years, lacing some of the birds’ diets with mercury. The team reports in The Proceedings of the Royal Society B that 55% of male birds in the group exposed to the highest level of mercury, 0.3 parts per million, formed mating pairs with other males. Malemale pairs can occur in the wild when females are unavailable, but these birds had an ample supply of mates. Although the mechanism is unknown, the study suggests that mercury, a common pollutant from coal-burning power plants, may threaten the survival of ibises and other species, as no laws exist to protect them from exposure. http://scim.ag/mercury-changes
sonal flu—were a poor match for H1N1. They recognized the virus and latched on to it but weren’t able to stop it from replicating, says Polack. Unable to fight back, the system spiraled out of control, Polack speculates. Instead of punching holes in the viruses, the C4d-antibody complexes punctured the victims’ veins, flooding their lungs with water and plasma, the team reports in Nature Medicine. It makes sense that the old and the young didn’t have this strange reaction, Polack says. Young children and infants have few or no antibodies against seasonal flu strains, whereas elderly people had antibodies to an earlier H1N1 strain, known to be a much better match for the 2009 version. http://scim.ag/H1N1-victims Read the full postings, comments, and more at http://news.sciencemag. org/sciencenow.
CREDITS (TOP TO BOTTOM): JOSH WICKHAM/UF/IFAS; FERNANDO POLACK
www.sciencemag.org
SCIENCE
VOL 330
10 DECEMBER 2010
1467
Published by AAAS
Downloaded from www.sciencemag.org on December 10, 2010
