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.
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>
On the morning of April 12, 1955, newsrooms across the United States inked headlines onto newsprint: the Salk Polio vaccine was "safe, effective, and potent." This was long-awaited news. Americans had limped through decades of fear, unaware of what caused polio or how to cure it, faced with the disease's terrifying, visible power to paralyze and kill, particularly children.
The announcement of the polio vaccine was celebrated with noisy jubilation: church bells rang, factory whistles sounded, people wept in the streets. Within weeks, mass inoculation began as the nation put its faith in a vaccine that would end polio.
Today, most of us are blissfully ignorant of child polio deaths, making it easier to believe that we have not personally benefited from the development of vaccines. According to Dr. Steven Pinker, cognitive psychologist and author of the bestselling book Enlightenment Now, we've become blasé to the gifts of science. "The default expectation is not that disease is part of life and science is a godsend, but that health is the default, and any disease is some outrage," he says.
The Rise and Fall of Public Trust<p>When the polio vaccine was released in 1955, "we were nearing an all-time high point in public trust," says Matt Baum, Harvard Kennedy School professor and lead author of <a href="http://www.kateto.net/covid19/COVID19%20CONSORTIUM%20REPORT%2013%20TRUST%20SEP%202020.pdf" target="_blank" rel="noopener noreferrer"><u>several</u></a> <a href="https://shorensteincenter.org/wp-content/uploads/2020/09/COVID19-CONSORTIUM-REPORT-14-MISINFO-SEP-2020.pdf" target="_blank" rel="noopener noreferrer"><u>reports</u></a> measuring public trust and vaccine confidence. Baum explains that the U.S. was experiencing a post-war boom following the Allied triumph in WWII, a popular Roosevelt presidency, and the rapid innovation that elevated the country to an international superpower.</p><p> The 1950s witnessed the emergence of nuclear technology, a space program, and unprecedented medical breakthroughs, adds Emily Brunson, Texas State University anthropologist and co-chair of the Working Group on Readying Populations for COVID-19 Vaccine. "Antibiotics were a game changer," she states. While before, people got sick with pneumonia for a month, suddenly they had access to pills that accelerated recovery. </p><p>During this period, science seemed to hold all the answers; people embraced the idea that we could "come to know the world with an absolute truth," Brunson explains. Doctors were portrayed as unquestioned gods, so Americans were primed to trust experts who told them the polio vaccine was safe. </p>
The Shift in How We Consume Information<p>In the 1950s, the media created an informational consensus. The fundamental ideas the public consumed about the state of the world were unified. "People argued about the best solutions, but didn't fundamentally disagree on the factual baseline," says Baum. Indeed, the messaging around the polio vaccine was centralized and consistent, led by President Roosevelt's successful <a href="https://files.eric.ed.gov/fulltext/EJ978264.pdf" target="_blank" rel="noopener noreferrer"><u>March of Dimes crusade</u></a>. People of lower socioeconomic status with limited access to this information were <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1551508/?page=3" target="_blank" rel="noopener noreferrer"><u>less likely to have confidence</u></a> in the vaccine, but most people consumed <a href="https://www.c-span.org/video/?506891-1/a-special-report-polio" target="_blank" rel="noopener noreferrer"><u>media that assured them</u></a> of the vaccine's safety and <a href="https://www.cbsnews.com/news/the-salk-polio-vaccine-greatest-public-health-experiment-in-history/" target="_blank" rel="noopener noreferrer"><u>mobilized them</u></a> to receive it. </p><p>Today, the information we consume is no longer centralized—in fact, just the opposite. "When you take that away, it's hard for people to know what to trust and what not to trust," Baum explains. We've witnessed an increase in polarization and the technology that makes it easier to give people what they want to hear, reinforcing the human tendencies to vilify the other side and reinforce our preexisting ideas. When information is engineered to further an agenda, each choice and risk calculation made while navigating the COVID-19 pandemic <a href="https://www.nytimes.com/2020/12/19/opinion/sunday/coronavirus-science.html?referringSource=articleShare" target="_blank" rel="noopener noreferrer"><u>is deeply politicized</u></a>. </p><p>This polarization maps onto a rise in socioeconomic inequality and economic uncertainty. These factors, associated with a sense of lost control, prime people to embrace misinformation, explains Baum, especially when the situation is difficult to comprehend. "The beauty of conspiratorial thinking is that it provides answers to all these questions," he says. Today's insidious fragmentation of news media accelerates the circulation of mis- and disinformation, reaching more people faster, regardless of veracity or motivation. In the case of vaccines, skepticism around their origin, safety, and motivation is intensified. </p><p>Alongside the rise in polarization, Pinker says "the emotional tone of the news has gone downward since the 1940s, and journalists consider it a professional responsibility to cover the negative." Relentless focus on everything that goes wrong further erodes public trust and paints a picture of the world getting worse. "Life saved is not a news story," says Pinker, but perhaps it should be, he continues. "If people were more aware of how much better life was generally, they might be more receptive to improvements that will continue to make life better. These improvements don't happen by themselves."</p>
The Future Depends on Vaccine Confidence<p>So far, the U.S. has been unable to mitigate the catastrophic effects of the pandemic through social distancing, testing, and contact tracing. President Trump has <a href="https://www.washingtonpost.com/politics/bob-woodward-rage-book-trump/2020/09/09/0368fe3c-efd2-11ea-b4bc-3a2098fc73d4_story.html" target="_blank" rel="noopener noreferrer"><u>downplayed the effects and threat of the virus</u></a>, <a href="https://www.washingtonpost.com/outlook/2020/07/14/cdc-directors-trump-politics/" target="_blank" rel="noopener noreferrer"><u>censored experts and scientists</u></a>, <a href="https://www.theatlantic.com/science/archive/2020/06/america-giving-up-on-pandemic/612796/" target="_blank" rel="noopener noreferrer"><u>given up on containing the spread</u></a>, and <a href="https://www.nytimes.com/2020/09/16/world/covid-coronavirus.html" target="_blank" rel="noopener noreferrer"><u>mobilized his base to protest masks</u></a>. The Trump Administration failed to devise a national plan, so our national plan has defaulted to hoping for the <a href="https://www.politico.com/news/2020/08/26/nation-of-miracles-pence-coronavirus-vaccine-rnc-402949" target="_blank" rel="noopener noreferrer"><u>"miracle" of a vaccine</u></a>. And they are "something of a miracle," Pinker says, describing vaccines as "the most benevolent invention in the history of our species." In record-breaking time, three vaccines have arrived. But their impact will be weakened unless we achieve mass vaccination. As Brunson notes, "The technology isn't the fix; it's people taking the technology."</p><p> Significant challenges remain, including facilitating widespread access and supporting on-the-ground efforts to allay concerns and build trust with <a href="https://www.newyorker.com/news/daily-comment/african-american-resistance-to-the-covid-19-vaccine-reflects-a-broader-problem" target="_blank" rel="noopener noreferrer"><u>specific populations with historic reasons for distrust</u></a>, says Brunson. Baum predicts continuing delays as well as deaths from other causes that will be linked to the vaccine. </p><p> Still, there's every reason for hope. The new administration "has its eyes wide open to these challenges. These are the kind of problems that are amenable to policy solutions if we have the will," Baum says. He forecasts widespread vaccination by late summer and a bounce back from the economic damage, a "Good News Story" that will bolster vaccine acceptance in the future. And Pinker reminds us that science, medicine, and public health have greatly extended our lives in the last few decades, a trend that can only continue if we're willing to roll up our sleeves. </p>
Imagine this scenario: you get an annoying cough and a bit of a fever. When you wake up the next morning you lose your sense of taste and smell. That sounds familiar, so you head to a doctor's office for a Covid test, which comes back positive.
Your next step? An anti-Covid nasal spray of course, a "trickster drug" that will clear the once-dangerous and deadly virus out of the body. The drug works by tricking the coronavirus with decoy receptors that appear to be just like those on the surface of our own cells. The virus latches onto the drug's molecules "thinking" it is breaking into human cells, but instead it flushes out of your system before it can cause any serious damage.
This may sounds like science fiction, but several research groups are already working on such trickster coronavirus drugs, with some candidates close to clinical trials and possibly even becoming available late this year. The teams began working on them when the pandemic arrived, and continued in lockdown.
Biochemist David Baker, pictured in his lab at the University of Washington.