November 13 | 2020
Novel Technologies Could Make Coronavirus Vaccines More Stable for Worldwide Shipping
David Cox is a science and health writer based in the UK. He has a PhD in neuroscience from the University of Cambridge and has written for newspapers and broadcasters worldwide including BBC News, New York Times, and The Guardian. You can follow him on Twitter @DrDavidACox.
The vaccine from Pfizer will need to be stored at minus 70 degrees Celsius for worldwide distribution.
Unsplash
Ssendi Bosco has long known to fear the rainy season. As deputy health officer of Mubende District, a region in Central Uganda, she is only too aware of the threat that heavy storms can pose to her area's fragile healthcare facilities.
In early October, persistent rain overwhelmed the power generator that supplies electricity to most of the region, causing a blackout for three weeks. The result was that most of Mubende's vaccine supplies against diseases such as tuberculosis, diphtheria, and polio went to waste. "The vaccines need to be constantly refrigerated, so the generator failing means that most of them are now unusable," she says.
<p>This week, the global fight against the coronavirus pandemic received a major boost when Pfizer and their German partner BioNTech released interim results showing that their vaccine has proved more than 90 percent effective at preventing participants in their clinical trial from getting COVID-19.</p><p>But while Pfizer has already signed deals to supply the vaccine to the U.S., U.K., Canada, Japan and the European Union, Mubende's recent plight provides an indication of the challenges that distributors will face when attempting to ship a coronavirus vaccine around the globe, particularly to low-income nations.</p>
<p>Experts have estimated that somewhere between <a href="https://theconversation.com/creating-a-covid-19-vaccine-is-only-the-first-step-itll-take-years-to-manufacture-and-distribute-144352" target="_blank" rel="noopener noreferrer"><u>12 billion and 15 billion</u></a> doses will be needed to immunize the world's population against COVID-19, a staggering scale, and one that has never been attempted before. "The logistics of distributing COVID-19 vaccines have been described as one of the biggest challenges in the history of mankind," says Göran Conradson, managing director of Swedish vaccine manufacturer Ziccum.</p><p>But even these estimates do not take into account the potential for vaccine spoilage. Every year, the World Health Organization estimates that over <a href="https://www.weforum.org/agenda/2018/07/the-biggest-hurdle-to-universal-vaccination-might-just-be-a-fridge" target="_blank" rel="noopener noreferrer"><u>half of the world's vaccines</u></a> end up being wasted. This happens because vaccines are fragile products. From the moment they are made, to the moment they are administered, they have to be kept within a tightly controlled temperature range. Throughout the entire supply chain – transportation to an airport, the flight to another country, unloaded, distribution via trucks to healthcare facilities, and storage – they must be refrigerated at all times. This is known as the cold chain, and one tiny slip along the way means the vaccines are ruined.</p><p>"It's a chain, and any chain is only as strong as its weakest link," says Asel Sartbaeva, a chemist working on vaccine technologies at the University of Bath in the U.K.</p><p>For COVID-19, the challenge is even greater because some of the leading vaccine candidates need to be kept at <em>ultracold</em> temperatures. Pfizer's vaccine, for example, must be kept at <a href="https://www.marketwatch.com/story/moderna-and-pfizers-covid-19-vaccine-candidates-require-ultra-low-temperatures-raising-questions-about-storage-distribution-2020-08-27" target="_blank" rel="noopener noreferrer"><u>-70 degrees Celsius</u></a>, the kind of freezer capabilities rarely found outsides of specialized laboratories. Transporting such a vaccine across North America and Europe will be difficult enough, but supplying it to some of the world's poorest nations in Asia, Africa and South America -- where only 10 percent of healthcare facilities have reliable electricity -- might appear virtually impossible.</p><p>But technology may be able to come to the rescue.</p>
Making Vaccines Less Fragile
<p>Just as the world's pharmaceutical companies have been racing against the clock to develop viable COVID-19 vaccine candidates, scientists around the globe have been hastily developing new technologies to try and make vaccines less fragile. Some approaches involve various chemicals that can be added to the vaccine to make them far more resilient to temperature fluctuations during transit, while others focus on insulated storage units that can maintain the vaccine at a certain temperature even if there is a power outage.<br></p><p>Some of these concepts have already been considered for several years, but before COVID-19 there was less of a commercial incentive to bring them to market. "We never felt that there is a need for an investment in this area," explains Sam Kosari, a pharmacist at the University of Canberra, who researches the vaccine cold chain. "Some technologies were developed then to assist with vaccine transport in Africa during Ebola, but since that outbreak was contained, there hasn't been any serious initiative or reward to develop this technology further."</p><p>In her laboratory at the University of Bath, Sartbaeva is using silica - the main constituent of sand – to encase the molecular components within a vaccine. Conventional vaccines typically contain protein targets from the virus, which the immune system learns to recognize. However, when they are exposed to temperature changes, these protein structures degrade, and lose their shape, making the vaccine useless. Sartbaeva compares this to how an egg changes its shape and consistency when it is boiled.</p><p>When silica is added to a vaccine, it molds to each protein, forming little protective cages around them, and thus preventing them from being affected by temperature changes. "The whole idea is that if we can create a shell around each protein, we can protect it from physically unravelling which is what causes the deactivation of the vaccine," she says.</p><p>Other scientists are exploring similar methods of making vaccines more resilient. Researchers at the Jenner Institute at the University of Oxford recently conducted a clinical trial in which they added carbohydrates to a dengue vaccine, to assess whether it became easier to transport. </p><p>Both research groups are now hoping to collaborate with the COVID-19 vaccine candidates being developed by AstraZeneca and Imperial College, assuming they become available in 2021.</p><p>"It's good we're all working on this big problem, as different methods could work better for different types of COVID-19 vaccines," says Sartbaeva. "I think it will be needed."</p>Next-Generation Vaccine Technology
<p>While these different technologies could be utilized to try and protect the first wave of COVID-19 vaccines, efforts are also underway to develop completely new methods of vaccination. Much of this research is still in its earliest stages, but it could yield a second generation of COVID-19 vaccine candidates in 2022 and beyond.<br></p><p>"After the first round of mass vaccination, we could well observe regional outbreaks of the disease appearing from time to time in the coming years," says Kosari. "This is the time where new types of vaccines could be helpful."</p><p>One novel method being explored by Ziccum and others is dry powder vaccines. The idea is to spray dry the final vaccine into a powder form, where it is more easily preserved and does not require any special cooling while being transported or stored. People then receive the vaccine by inhaling it, rather than having it injected into their bloodstream.</p><p>Conradson explains that the concept of dry powder vaccines works on the same principle as dried food products. Because there is no water involved, the vaccine's components are far less affected by temperature changes. "It is actually the water that leads to the destruction of potency of a vaccine when it gets heated," he says. "We're looking to develop a dry powder vaccine for COVID-19 but this will be a second-generation vaccine. At the moment there are more than 200 first-generation candidates, all of which are using conventional technologies due to the timeframe pressures, which I think was the correct decision."</p><p>Dry powder COVID-19 vaccines could also be combined with microneedle patches, to allow people to self-administer the vaccine themselves in their own home. Microneedles are miniature needles – measured in millionths of a meter – which are designed to deliver medicines through the skin with minimal pain. So far, they have been used mainly in cosmetic products, but many scientists are working to use them to deliver drugs or vaccines.</p><p>At Georgia Institute of Technology in Atlanta, Mark Prausnitz is leading a couple of projects looking at incorporating COVID-19 vaccines into microneedle patches with the hope of running some early-stage clinical trials over the next couple of years. "The advantage is that they maintain the vaccine in a stable, dry state until it dissolves in the skin," he explains. </p><p>Prausnitz and others believe that once the first generation of COVID-19 vaccines become available, biotech and pharmaceutical companies will show more interest in adapting their products so they can be used in a dried form or with a microneedle patch. "There is so much pressure to get the COVID vaccine out that right now, vaccine developers are not interested in incorporating a novel delivery method," he says. "That will have to come later, once the pressure is lessened." </p>The Struggle of Low-Income Nations
<p>For low-income nations, time will only tell whether technological advancements can enable them to access the first wave of licensed COVID-19 vaccines. But reports already suggest that they are in danger of becoming an afterthought in the race to procure vaccine supplies.</p><p>While initiatives such as COVAX are attempting to make sure that vaccine access is equitable, high and middle-income countries have already inked deals to secure 3.8 billion doses, with options for another 5 billion. One particularly sobering <a href="https://globalhealth.duke.edu/news/will-low-income-countries-be-left-behind-when-covid-19-vaccines-arrive" target="_blank" rel="noopener noreferrer"><u>study</u></a> by the Duke Global Health Innovation Center has suggested that such hoarding means many low-income nations may not receive a vaccine until 2024.</p><p>For Bosco and the residents of Mubende District in Uganda, all they can do is wait. In the meantime, there is a more pressing problem: fixing their generators. "We hope that we can receive a vaccine," she says. "But the biggest problem will be finding ways to safely store it. Right now we cannot keep any medicines or vaccines in the conditions they need, because we don't have the funds to repair our power generators." </p>
Keep Reading
Keep Reading
David Cox is a science and health writer based in the UK. He has a PhD in neuroscience from the University of Cambridge and has written for newspapers and broadcasters worldwide including BBC News, New York Times, and The Guardian. You can follow him on Twitter @DrDavidACox.
November 24 | 2020
You're invited: A Fireside Chat with the CDC's Dr. Nancy Messonnier
This free, virtual event will address public concerns about the coronavirus vaccines' speed and safety, and their pending rollout.
Alexander Limbach/Adobe
EVENT INFORMATION
________
DATE:
<p><strong>Monday, December 7th, 2020 12:00pm - 12:45pm PST</strong></p><p>This virtual fireside chat will provide Dr. Nancy Messonnier, Director of the National Center for Immunization and Respiratory Diseases, an opportunity to speak candidly to the public about the scientific integrity of the CDC, to address concerns regarding the speed and safety of coronavirus vaccines, and to discuss the government's work to distribute them quickly and equitably. She will appear in conversation with Nsikan Akpan, science editor at National Geographic. A public Q&A will follow the fireside chat.</p><p><strong>CONTACT:</strong></p><p>kira@goodinc.com</p><p><strong>LOCATION:</strong></p><p>Zoom webinar</p><p><strong>HOSTS:</strong></p><p>LeapsMag and the Aspen Institute Science & Society Program</p><h2><a href="https://aspeninst.zoom.us/webinar/register/WN_T2BsBchITQWbBrm3ik5h-A" target="_blank">REGISTER NOW</a></h2><p>________</p><p><strong>Nancy Messonnier, MD<br/></strong>Director of the National Center for Immunization and Respiratory Diseases, CDC</p><p><br/></p><p class="shortcode-media shortcode-media-rebelmouse-image">
<img type="lazy-image" data-runner-src="https://leapsmag.com/media-library/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDgwMjU1Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMTU5MDIzOX0.o8laaOoDYKZ2uGECiQSwCSEvch8oUx4WTET1Vk2ZaaU/image.jpg?width=980" id="6547b" class="rm-shortcode" data-rm-shortcode-id="0474d5dd6a6df6c61c2470743fd4c763" data-rm-shortcode-name="rebelmouse-image" />
<small class="image-media media-photo-credit" placeholder="Add Photo Credit..."> LAUREN BISHOP - CDC </small></p><p><br/></p><p><strong>Nsikan Akpan</strong></p><p>Science Editor, National Geographic</p><p class="shortcode-media shortcode-media-rebelmouse-image">
<img type="lazy-image" data-runner-src="https://leapsmag.com/media-library/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDgwMjU2OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMDQzNjU3Nn0.uH_LPNFvedFIX3bian8w15AX1TqXThudBmi6yThETYc/image.jpg?width=980" id="75ec5" class="rm-shortcode" data-rm-shortcode-id="c6f656bb9dc181adde818e78b4c73f37" data-rm-shortcode-name="rebelmouse-image" />
</p>
Keep Reading
Keep Reading
Kira Peikoff is a journalist whose work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and son.
November 24 | 2020
How One Doctor Single-Handedly Saved Countless Babies from Birth Defects
President John F. Kennedy gave Dr. Frances Oldham Kelsey the nation's highest federal civilian service award in 1962, saying she had "prevented a major tragedy of birth deformities."
The White House
In July 1956, a new drug hit the European market for the first time. The drug was called thalidomide – a sedative that was considered so safe it was available without a prescription.
Sedatives were in high demand in post-war Europe – but barbiturates, the most widely-used sedative at the time, caused overdoses and death when consumers took more than the recommended amount. Thalidomide, on the other hand, didn't appear to cause any side effects at all: Chemie Grünenthal, thalidomide's manufacturer, dosed laboratory rodents with over 600 times the normal dosage during clinical testing and had observed no evidence of toxicity.
The drug therefore was considered universally safe, and Grünenthal supplied thousands of doctors with samples to give to their patients. Doctors were encouraged to recommend thalidomide to their pregnant patients specifically because it was so safe, in order to relieve the nausea and insomnia associated with the first trimester of pregnancy.
<p>By 1960, Thalidomide was being sold in countries throughout the world, and the United States was expected to soon follow suit. Dr. Frances Oldham Kelsey, a pharmacologist and physician, was hired by the Food and Drug Administration (FDA) in September of that year to review and approve drugs for the administration. Immediately, Kelsey was tasked with approving thalidomide for commercial use in the United States under the name Kevadon. Kelsey's approval was supposed to be a formality, since the drug was so widely used in other countries.</p><p>But Kelsey did something that few people expected – she paused. Rather than approving the drug offhand as she was expected to do, Kelsey asked the manufacturer – William S. Merrell Co., who was manufacturing thalidomide under license from Chemie Grünenthal – to supply her with more safety data, noting that Merrell's application for approval relied mostly on anecdotal testimony. Kelsey – along with her husband who worked as a pharmacologist at the National Institutes of Health (NIH) — was highly suspicious of a drug that had no lethal dose and no side effects. "It was just too positive," Kelsey said later. "This couldn't be the perfect drug with no risk."</p><p>At the same time, rumors were starting to swirl across Europe that thalidomide was not as safe as everyone had initially thought: Physicians were starting to notice an "unusual increase" in the birth of severely deformed babies, and they were beginning to suspect thalidomide as the cause. The babies, whose mothers had all taken thalidomide during pregnancy, were born with conditions like deafness, blindness, congenital heart problems, and even phocomelia, a malformation of the arms and legs. Doctors and midwives were also starting to notice a sharp rise in miscarriages and stillbirths among their patients as well.</p>
<blockquote>Kelsey's skepticism was rewarded in November 1961 when thalidomide was yanked abruptly off the market, following a growing outcry that it was responsible for hundreds of stillbirths and deformities.</blockquote>
<p><strong></strong>Kelsey had heard none of these rumors, but she did know from her post-doctoral research that adults could metabolize drugs differently than fetuses – in other words, a drug that was perfectly safe for adults could be detrimental to a patient's unborn child. Noting that thalidomide could cross the placental barrier, she asked for safety data, such as clinical trials, that showed specifically the drug was non-toxic for fetuses. Merrell supplied Kelsey with anecdotal data – in other words, accounts from patients who attested to the fact that they took thalidomide with no adverse effects – but she rejected it, needing stronger data: clinical studies with pregnant women included. </p><p> <br> The drug company was annoyed at what they considered Kelsey's needless bureaucracy. After all, Germans were consuming around 1 million doses of thalidomide every day in 1960, with lots of anecdotal evidence that it was safe, even among pregnant women. As the holidays approached – the most lucrative time of year for sedative sales – Merrell executives started hounding Kelsey to approve thalidomide, even phoning her superior and paying her visits at work. But Kelsey was unmovable. Kelsey's skepticism was solidified in December 1960, when she read a letter published in the British Medical Journal from a physician. In the letter, the author warned that his long-term thalidomide patients were starting to report pain in their arms and legs. <br> <br> "The burden of proof that the drug is safe … lies with the applicant," Kelsey wrote in a letter to Merrell executive Joseph F. Murray in May of 1961. Despite increasing pressure, Kelsey held fast to her insistence that more safety data – particularly for fetuses – was needed. </p><p>Kelsey's skepticism was rewarded in November 1961 when Chemie Grünenthal yanked thalidomide off the market overseas, following a growing outcry that it was responsible for hundreds of stillbirths and deformities. In early 1962, Merrell conceded that the drug's safety was unproven in fetuses and formally withdrew its application at the FDA. </p><p>Thanks to Kelsey, the United States was spared the effects of thalidomide – although countries like Europe and Canada were not so lucky. Thalidomide remained in people's homes under different names long after it was pulled from the market, and so women unfortunately continued to take thalidomide during their pregnancies, unaware of its effects. All told, thalidomide is thought to have caused around 10,000 birth defects and anywhere from 5,000 to 7,000 miscarriages. Many so-called "thalidomide babies" are now adults living with disabilities. </p>
<img lazy-loadable="true" src="https://leapsmag.com/media-library/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDgwMjg0OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyMTY2MTE2OH0.AaTQP9wGpud8YBoQ6Y-16ockDDviTlsgICxi4ZL6boE/image.jpg?width=980" id="52c09" class="rm-shortcode" data-rm-shortcode-id="d1c3d76a193123f09add737ad263ea05" data-rm-shortcode-name="rebelmouse-image" />
Niko von Glasow, born in 1960, is a German film director and producer who was born disabled due to the side effects of thalidomide.
Wikimedia Commons
<p>Just two years after joining the FDA, Kelsey was presented with the President's Award for Distinguished Federal Civilian Service and was appointed as the head of the Investigational Drug Branch at the FDA. Not only did Kelsey save the U.S. public from the horrific effects of thalidomide, but she forever changed the way drugs were developed and approved for use in the United States: Drugs now need to not only be proven safe and effective, but adverse drug reactions need to be reported to the FDA and informed consent must be obtained by all participants before they volunteer for clinical trials. Today, the United States is safer because of Frances Kelsey's bravery.</p>
Keep Reading
Keep Reading
Sarah Watts is a health and science writer based in Chicago. Follow her on Twitter at @swattswrites.