Time and again, Martin Moore’s children get sick with a cold. He hauls them to their doctor, who then informs him that there’s nothing to be done aside from taking them home and waiting it out. 
 
 The experience is maddening for Moore — especially because he’s a virologist. For everything that virologists have learned about rhinoviruses — the cause of the majority of colds — they have not invented a vaccine for them. 
 
 In 2013, Moore wondered if he could make one. He consulted a rhinovirus expert for some advice. Instead, the expert told him, “Oh, there will never be a vaccine for rhinovirus — it’s just not possible.” 
 
 “I thought, ‘Well, let’s look into that,’” recalled Moore, an associate professor at Emory University and a research scholar at Children’s Healthcare of Atlanta. 
 
 Three years later, Moore and his colleagues now have a vaccine that has shown promising results in trials on macaques. The monkeys were able to produce antibodies against many types of rhinoviruses. Moore and his colleagues are now following up on those results with more research and hope to move soon to human trials. 
 
 They’re not alone, however. Other research groups, based at universities and at pharmaceutical companies, are making advances with vaccines of their own. After decades of disappointment and resignation, scientists think the common cold may at last be beatable. 
 
 “There’s a huge amount going on,” said Gary McLean, of Imperial College London, who is working on another vaccine. 
 
 Rhinoviruses were discovered in the early 1960s, and soon afterward a number of researchers tried to make vaccines against them. They soon discovered that rhinoviruses were a wily foe. They’ve evolved into many different forms, and so antibodies to one form (known as a serotype) usually don’t work against any others. 
 
 The last report on a human cold vaccine trial was published in 1975. Since then, there’s been nothing. 
 
 In recent years, however, some scientists have been trying to drum up interest again in a vaccine. They’ve demonstrated that the rhinovirus is not as harmless as it once seemed. “It’s getting more respect as a pathogen,” said Dr. James Gern, a pediatrician at the University of Wisconsin School of Medicine who studies colds. 
 
 Colds take an enormous economic toll on families. Between sick days and parents staying home to care for their children, colds drain an estimated $25 billion a year from workplace productivity in the United States. 
 
 Colds can also cause more physical harm than scientists previously appreciated. When most people get a cold, the rhinoviruses stay in their nose. But Gern and others have discovered that some types of rhinovirus can invade deep into the lungs. Many cases of childhood pneumonia turn out to be caused by rhinoviruses. 
 
 Rhinoviruses are especially dangerous for people who already have certain chronic disorders such as asthma, cystic fibrosis, or chronic obstructive pulmonary disease. Even a mild cold can trigger runaway inflammation in their lungs. It turns out that the majority of asthma attacks are brought on by rhinoviruses. 
 
 “Rhinovirus can cause more disease in certain people, and when I say ‘certain people,’ I mean a lot of people,” said Gern. 
 
 If someone with COPD ends up in the hospital due to a cold-triggered attack, doctors can try to tamp down the inflammation, but the best treatments are not very effective. “A vaccine would stop all that in its tracks before it gets started,” said McLean. 
 
 Over the past decade, McLean and others at Imperial have been studying colds in mice to find new inspirations for a vaccine. They exposed the animals to different parts of rhinoviruses to see how their immune systems responded. 
 
 The cold vaccines that scientists had tested in the 1960s and 1970s had prompted the immune system to make antibodies only to the proteins on the surface of the virus shells. When the vaccinated volunteers got infected again, those antibodies could grab onto the rhinoviruses and summon the immune system to destroy them. 
 
 The problem with this approach is that each serotype has surface proteins with different shapes. Antibodies that can grab onto one serotype slip off another. 
 
 But our immune system can also fight rhinovirus in another way — after they’ve invaded our cells. Once viruses have worked their way inside, their shells break open and they dump out internal proteins and genes. The cells then use these molecules to make new viruses. 
 
 It turns out that cells can grab some of these molecules and push them to their surface. It’s as if they’re pushing a home invasion alarm. Immune cells can learn to recognize these viral proteins. They instruct infected cells to kill themselves and slow down an infection. 
 
 McLean and his colleagues set out to build a new vaccine based on this alarm defense. They whipped up batches of internal proteins from rhinoviruses and injected them into mice. The scientists found that the immune system of the mice could learn to recognize the proteins. If they mixed rhinoviruses with mouse blood, immune cells aggressively attacked infected cells. 
 
 What’s especially exciting about this approach is that the proteins from one type of rhinovirus can trigger a response to other types as well. That’s because the internal proteins they’re targeting are pretty much the same from one type to another. It’s probably impossible for them to evolve into different shapes, because they’d stop doing their essential work. 
 
 When Martin Moore got into the cold vaccine game, he didn’t try to find a new strategy the way the Imperial scientists did. Instead, he tried to update an approach that had been pioneered by University of Virginia scientists in the 1970s. 
 
 The Virginia team had picked out 10 different serotypes and combined them into one shot. 
 
 “It produced some antibody, but it wasn’t great,” said Bruce Hamory, one of the Virginia researchers. “If you challenged someone with a strain that wasn’t in the vaccine, there was no cross-protection.” 
 
 But Moore decided the idea was sound. The only problem was that scientists in the 1970s just didn’t have the tools to make it work. In the 21st century, those tools were now at hand. 
 
 A lot of other scientists didn’t share Moore’s optimism. “It was definitely a risk,” he said. “We broke the bank, people left the lab. You name it. But I just felt this is what I needed to do.” 
 
 To make a new vaccine, Moore needed a lot of rhinoviruses. He also needed a lot of different types of rhinoviruses. So far, scientists have identified 160 types from people with colds. 
 
 To get his hands on the pathogens, Moore contacted James Gern. He knew that Gern has gathered rhinoviruses from his patients for over two decades in order to do research on colds. 
 
 “We probably have one of the world’s biggest collections of kid snot,” said Gern. 
 
 Out of his snot collection, Gern and his colleagues can isolate many different types of rhinoviruses. They can then extract the genes for those viruses and store them. When they want to study a particular type, they simply inject the genes into human cells and let them churn out new viruses. This gene-based method lets them make viruses much faster than in the 1970s, and they can be sure they’re making exactly the type they want. 
 
 For a trial vaccine, Moore decided to ramp up Hamory’s 10-type vaccine to 50. He and his colleagues packed a large number of each type of rhinovirus into a single shot. 
 
 They injected the vaccine into macaques and then later drew blood from the monkeys. When they mixed the viruses into the blood, they got a strong antibody response to 49 out of the 50 types. Moore and his colleagues published the results in Nature Communications, and they’re now moving forward with some additional studies that they hope will open the way to a human trial. 
 
 Meanwhile, the Imperial team has filed a patent on its internal-protein vaccine and is also moving in the same direction. “To convince people to part with large sums of money, you need a lot of preclinical data. And we’ve got about as much as we can at the moment,” said McLean. 
 
 It’s still an open question which strategy will win out. It’s even possible that both will fail. McLean and his colleagues still need to show that a vaccine using a single protein can protect against the full range of rhinoviruses that cause the most colds. 
 
 McLean also wonders how well Moore’s 50-type vaccine would work in the real world. “It’s a great paper, but it’s not showing anything new except for being able to pack in 50 types of the virus into one little injection,” said McLean. “Great, you’re going to get 50 immune responses. That’s going to work for those 50, but it might not work for an extra 30.” 
 
 Gern agrees that’s a concern. “If it really takes 130 types, that’s a lot of manufacturing that would go into one vaccine,” he said. He says it might make sense for now to tailor Moore’s vaccine for just one group of people. 
 
 Only certain types of rhinovirus appear to pose the biggest risk to people with COPD, for example. Scientists might start by testing a cold vaccine for COPD. If that works, they could think about scaling up to a cold vaccine for more people. 
 
 After giving up on a cold vaccine 40 years ago, Hamory likes to hear people talk this way again. “I’m tremendously excited,” he said. “I think it’s absolutely spectacular that people are going back to an important problem that’s laid fallow for so many years.” 
 
 This article originally published at STAT here ||||| Rhinoviruses are the predominant cause of the common cold and also exacerbate asthma. Photo from Thinkstock. 
 
 The vaccine tested by Emory/CHOA researchers does not cover all known rhinoviruses, but it does stimulate antibodies against 50 of them. 
 
 Scientists are making the case that a vaccine against rhinoviruses, the predominant cause of the common cold, is achievable. 
 
 The quest for a vaccine against rhinoviruses may have seemed quixotic, because there are more than 100 varieties circulating around the world. Even so, the immune system can handle the challenge, researchers from Emory University School of Medicine and Children’s Healthcare of Atlanta say. 
 
 Vaccines that combine dozens of varieties of rhinovirus at once are effective in stimulating antiviral antibodies in mice and monkeys, the researchers report in Nature Communications. The paper was also posted on Biorxiv before publication. 
 
 “We think that creating a vaccine for the common cold can be reduced to technical challenges related to manufacturing,” says Martin Moore, PhD, associate professor of pediatrics at Emory University School of Medicine. 
 
 Rhinoviruses are the most common cause of the common cold; other viruses such as respiratory syncytial virus, parainfluenza virus and adenoviruses can cause them too. Rhinoviruses also exacerbate asthma attacks. Although they come in many varieties, rhinoviruses do not drift to the same degree that influenza viruses do, Moore says. 
 
 Researchers showed in the 1960s that it was possible to vaccinate people against one variety of rhinovirus and prevent them from getting sick when challenged with samples of the same virus. The trouble was the sheer diversity of rhinoviruses – or that’s how it appeared at the time. 
 
 “It’s surprising that nobody tried such a simple solution over the last 50 years. We just took 50 types of rhinovirus and mixed them together into our vaccine, and made sure we had enough of each one,” Moore says. “If we make a vaccine with 50 or 100 variants, it's the same amount of total protein in a single dose of vaccine. The variants are like a bunch of slightly different Christmas ornaments, not really like 50 totally different vaccines mixed.” 
 
 A mixture of 25 types of inactivated rhinovirus can stimulate neutralizing antibodies against all 25 in mice, and a mixture of 50 types can do the same thing in rhesus macaques. In this paper, antibodies generated in response to the vaccine were tested for their ability to prevent the virus from infecting human cells in culture. However, the vaccines were not tested for their ability to stop animals from getting sick. 
 
 “There are no good animal models of rhinovirus replication,” Moore says. “The next step would be human challenge models with volunteers, which are feasible because the virus is not very pathogenic.” 
 
 Emory has optioned the vaccine technology to a startup company, Meissa Vaccines, Inc., which is pursuing a product development plan with support from the National Institute of Allergy and Infectious Diseases’ vaccine manufacturing services. 
 
 The co-first authors of the paper are assistant professor of pediatrics Sujin Lee, PhD, and research specialist Minh Trang Nguyen. The research was supported by the National Institute of Allergy and Infectious Diseases (R01AI087798, U19AI095227) and a pilot grant from the Emory/Children’s/Georgia Tech Center for Childhood Infections and Vaccines. Experiments with rhesus macaques were performed at Yerkes National Primate Research Center. 
 
 Moore co-founded and serves as chief scientific officer for Meissa Vaccines, Inc. Lee, Nguyen and Moore are co-inventors in a patent application describing the rhinovirus vaccine reported in the Nature Communications paper. ||||| Nasal gene spray inspired by llama antibodies could prevent all types of flu 
 
 Four llama antibodies and a harmless virus: This outlandish recipe could be the basis of a nasal spray designed to foil infection from all strains of influenza. The spray, containing a virus engineered to make a protein derived from the llama antibodies, has passed its first animal test, protecting mice from every known flu strain that infects humans, a research team reports. 
 
 Although the strategy must go through more testing before human trials can begin, researchers who have struggled to develop a "universal" vaccine against the highly mutable flu virus say it merits serious attention. The nasal spray could prove a boon to the elderly, who typically suffer most from flu and get only weak protection from existing vaccines. And unlike traditional influenza vaccines, which are tailormade each flu season to match the viruses in circulation, it could be stockpiled as protection against a flu pandemic. "This is a great story and shows the power of antibody engineering," says immunologist Antonio Lanzavecchia, a leading flu vaccine researcher at the Institute for Research in Biomedicine in Bellinzona, Switzerland. 
 
 Antibody engineer Joost Kolkman at Janssen Infectious Diseases in Beerse, Belgium, and his colleagues thought an unusual class of antibodies made by llamas and their camel cousins might serve as a weapon against flu. These antibodies are unusually small because they lack the "light" peptide chain that normally bulks up each arm of the Y-shaped proteins. Researchers can further pare down the remaining "heavy" chains to create so-called nanobodies, able to reach into crevices of viruses that their full-size counterparts can't touch. 
 
 To create nanobodies against the flu, the Janssen group injected llamas with a vaccine containing three different influenza viruses, as well as the viral surface protein, hemagglutinin, from two other flu strains. They then harvested four antibodies that each neutralized many flu strains. Ultimately, the team was able to engineer a gene that expressed a protein made up of nanobodies derived from all four antibodies. "It's very easy to link the domains together into one single molecule," Kolkman says. They spliced the gene into a benign adenovirus-associated virus (AAV) that's used in gene therapy experiments. 
 
 Test tube studies showed the four-in-one antibody prevented infection by 60 different influenza viruses from both the type A and B groups that infect people. "It's been quite hard to find an antibody that neutralizes both A and B," says Ian Wilson, a structural biologist at the Scripps Research Institute in San Diego, California, who helped work out how the nanobodies bound to the virus. 
 
 Mice given the synthetic antibody—delivered either by squirting the doctored virus into their noses of the mice or by infusing the protein directly into their circulation—had significantly higher survival rates than untreated rodents when injected with a variety of influenza strains. Wilson, who has published more than 50 papers on influenza antibodies, says he's never seen one with greater breadth and potency. Because AAVs can persist for months, the strategy could offer extended production. "Hopefully it would last the entire flu season in humans," Wilson says. 
 
 Immunologist James Crowe, an influenza antibody specialist and vaccine developer at Vanderbilt University in Nashville, cautions that human immune systems may see the llama-derived proteins as foreign and develop antibodies against them. He also notes that although AAV-based treatments are being tested for life-threatening diseases, giving the virus as a flu preventive would face more intense scrutiny from regulators. "The bar for putting AAV in a healthy individual is going to be very high," Crowe says. ||||| A nurse in Switzerland holds a dose of experimental vaccine developed at the National Institutes of Health. (Photo: JEAN-CHRISTOPHE BOTT, EPA) 
 
 The first experimental Ebola vaccine to be tested in humans appears safe and capable of stimulating the immune system, according to a small, early clinical trial at the National Institutes of Health. 
 
 But the dose of vaccine required to spur the immune system into action is very high, which could make it harder for its manufacturer to quickly produce it, experts say. 
 
 Still, the results of the 20-person study, launched in September, are promising enough to proceed to a study in West Africa with thousands of participants, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. These trials could take some time, because researchers will have to wait to see if people who are vaccinated contract Ebola. 
 
 The vaccine, developed by the NIH, uses a chimpanzee cold virus, called an adenovirus, to carry genes from two types of Ebola viruses into human cells, Fauci said. The vaccine – which will be manufactured by GlaxoSmithKline -- can't cause Ebola. It's also being tested in the United Kingdom, Mali and Switzerland. 
 
 The study found that all 20 people who received the vaccine made antibodies against Ebola, according to an article in The New England Journal of Medicine. Some people who got the vaccine also produced immune cells, called T-cells, that fight off infections. 
 
 People who got a higher dose of vaccine had a stronger immune response, the study says. The vaccine appeared safe. The only side effects were short-lived fevers in two people who received the higher dose. 
 
 Peter Hotez, dean of the National School of Tropical Medicine, said he's concerned that it took a high dose of vaccine to produce an immune system reaction. That could make it hard to produce enough of the vaccine to save lives in the West African outbreak, where Ebola has infected 15,351 people and killed 5,459, mostly in Guinea, Sierra Leone and Liberia. 
 
 The NIH vaccine appears to require tens of thousands more viral particles to stimulate the immune system than a rival vaccine, developed by the Public Health Agency of Canada, called the VSV vaccine, said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. That vaccine uses vesicular stomatitis virus, which belongs to the same family as rabies, to carry Ebola genes into cells. Commercial rights to that vaccine have been sold to Merck. 
 
 "When time is of the essence, as it is during the current outbreak, the question is not, 'Can you make the vaccine?' but 'How soon can you make? And how much?' " Osterholm said. 
 
 Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said quarantines may discourage health workers from traveling to West Africa. (Photo: Alex Wong, Getty Images) 
 
 Thomas Geisbert, an Ebola expert at the University of Texas Medical Branch in Galveston, expressed another concern. 
 
 In animal studies, the NIH vaccine didn't protect for very long, and required a booster to provide long-lasting protection. 
 
 Although scientists have been working on Ebola vaccines for years, it wasn't until the outbreak in West Africa that large pharmaceutical companies showed interest in developing vaccines and bringing them to market, Geisbert now. 
 
 Now, nine Ebola vaccines are being tested, Fauci told Congress last week. 
 
 The NIH and Canadian vaccines are the furthest along. 
 
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– When an expert in rhinoviruses told Martin Moore in 2013 that there would never be a vaccine for the common cold, the Emory University professor thought to himself, "Well, let's look into that." Three years later, it appears his probing against the odds has paid off: Per a study published last month in the journal Nature, mice and macaque monkeys given a vaccine developed by Moore and his team have been able to work up antibodies against a variety of rhinoviruses, which most often are the cause of the common cold, Mashable reports. Not that Moore is the sole pioneer on this landscape: Other researchers at colleges and with pharma companies have been toiling away in labs seeking a similar remedy for the coughing, sneezing, and sniffling that the CDC notes is the main reason why kids miss school and grownups call in sick to work. Per an Emory press release, even though scientists in the '60s were able to develop a vaccine effective against one type of rhinovirus, it didn't work against the many other varieties that exist; Mashable pegs that figure at more than 160. So Moore mixed together 50 different rhinoviruses—gathered from immunologist James Gern, who keeps what he calls "one of the world’s biggest collections of kid snot"—into one vaccine, "like a bunch of slightly different Christmas ornaments." Post-vaccine, the monkeys had developed antibodies in their blood for 49 out of the 50 viruses; similar results were found in the mice. Moore is hoping to eventually test the vaccine out on humans. "We think that creating a vaccine for the common cold can be reduced to technical challenges related to manufacturing," he says. (Here's why colds are more common when the mercury drops.)