The coronavirus pandemic has claimed nearly 50,000 lives in the U.S. and continues to shutter businesses across the country. But amid the crisis, creatives are rising to the challenge to help others in need.
Besides donating masks and spreading creative messages of social distancing, some agencies aredesigning and selling custom merchandisethat have and raisedtens of thousands of dollars to support businesses and Americans heavily affectedby the crisis.
Dylan Hattem is founder and CEO of DS Projects, a digital agency he started when he left the ad tech world three years ago. In between doing work for clients like Adidas, Airbnb and Budweiser, Hattem has launched the COVID-19 Merch Initiative, a fundraiser that gives 100 percent of the proceeds from custom merchandise to local restaurants and restaurant groups across 20 U.S. states.
So far, sales are just shy of $90,000. With the shared challenges felt acrossthe board, togetherness and support has never been more important, says Hattem.
Hattem began the effort in March by selling one comical T-shirt that read: Bought this T-shirt and stayed the fuck home. It sold online for $40 and Hattem promoted the work on LinkedIn and Instagram at its own account @buythistshirt. In six days, the shirt sale had raised $40,000. In three weeks, it raised $63,000.
Hattem than began to partner with favorite local eateries in cities across the U.S. like Hattie B's in Nashville, The Flower Shop in New York, Grant Central Market in Los Angeles and Broad Street Oyster Co. in Malibu to sell custom shirts with their logos on the back and the original statement on the front. There are now 18 different restaurant T-shirts on sale for $40 each at thist-shirt.com. Hattem is using small, independent manufacturers on the East Coast to produce the shirts.
The World Health Organisation said this week it may be 18 months before a vaccine against the coronavirus is publicly available.
Let's explore why, even with global efforts, it might take this long.
China shared publicly the full RNA sequence of the virus now known as SARS-CoV-2 rather than COVID-19, which refers to the disease itself in the first half of January.
This kickstarted efforts to develop vaccines around the world, including at the University of Queensland and institutions in the US and Europe.
By late January, the virus was successfully grown outside China for the first time, by Melbourne's Doherty Institute, a critically important step. For the first time, researchers in other countries had access to a live sample of the virus.
Using this sample, researchers at CSIRO's high-containment facility (the Australian Animal Health Laboratory) in Geelong, could begin to understand the characteristics of the virus, another crucial step in the global effort towards developing a vaccine.
Vaccines have historically taken two to five years to develop. But with a global effort, and learning from past efforts to develop coronavirus vaccines, researchers could potentially develop a vaccine in a much shorter time.
No single institution has the capacity or facilities to develop a vaccine by itself. There are also more stages to the process than many people appreciate.
First, we must understand the virus's characteristics and behaviour in the host (humans). To do this, we must first develop an animal model.
Next, we must demonstrate that potential vaccines are safe and can trigger the right parts of the body's immunity, without causing damage. Then we can begin pre-clinical animal testing of potential vaccines, using the animal model.
Vaccines that successfully pass pre-clinical testing can then be used by other institutions with the capacity to run human trials.
Where these will be conducted, and by whom, has yet to be decided. Generally, it is ideal to test such vaccines in the setting of the current outbreak.
Finally, if a vaccine is found to be safe and effective, it will need to pass the necessary regulatory approvals. And a cost-effective way of making the vaccine will also need to be in place before the final vaccine is ready for delivery.
Each of these steps in the vaccine development pipeline faces potential challenges.
The international Coalition for Epidemic Preparedness Innovations has engaged our team in those first two steps: determining the characteristics of the current virus, then pre-clinical testing of potential vaccines.
While Melbourne's Doherty Institute and others have been instrumental in isolating the novel coronavirus, the next step for us is growing large amounts of it so our scientists have enough to work with. This involves culturing the virus in the lab (encouraging it to grow) under especially secure and sterile conditions.
The next challenge we face is developing and validating the right biological model for the virus. This will be an animal model that gives us clues to how the coronavirus might behave in humans.
Our previous work with SARS (severe acute respiratory syndrome) has given us a good foundation to build on.
SARS is another member of the coronavirus family that spread during 2002-03. Our scientists developed a biological model for SARS, using ferrets, in work to identify the original host of the virus: bats.
SARS and the new SARS-CoV-2 share about 80-90 percent of their genetic code. So our experience with SARS means we are optimistic our existing ferret model can be used as a starting point for work on the novel coronavirus.
We will also explore other biological models to provide more robust data and as a contingency.
There's also the strong possibility that SARS-CoV-2 will continue to mutate.
Being an animal virus, it has already likely mutated as it adapted first to another animal, and then jumping from an animal to humans.
Initially this was without transmission among people, but now it has taken the significant step of sustained human-to-human transmission.
As the virus continues to infect people, it is going through something of a stabilisation, which is part of the mutation process.
This mutation process may even vary in different parts of the world, for various reasons.
This includes population density, which influences the number of people infected and how many opportunities the virus has to mutate. Prior exposure to other coronaviruses may also influence the population's susceptibility to infection, which may result in variant strains emerging, much like seasonal influenza.
Therefore, it's crucial we continue to work with one of the latest versions of the virus to give a vaccine the greatest chance of being effective.
All this work needs to be done under stringent quality and safety conditions, to ensure it meets global legislative requirements, and to ensure staff and the wider community are safe.
Another challenge is manufacturing proteins from the virus needed to develop potential vaccines. These proteins are specially designed to elicit an immune response when administered, allowing a person's immune system to protect against future infection.
Fortunately, recent advances in understanding viral proteins, their structure and functions, has allowed this work to progress around the world at considerable speed.
Developing a vaccine is a huge task and not something that can happen overnight. But if things go to plan, it will be much faster than we've seen before.
So many lessons were learned during the SARS outbreak. And the knowledge the global scientific community gained from trying to develop a vaccine against SARS has given us a head-start on developing one for this virus.
Rob Grenfell, Director of Health and Biosecurity, CSIRO and Trevor Drew, Director of the Australian Animal Health Laboratory (AAHL), CSIRO.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
China could have a coronavirus vaccine ready for public release by early next year and one for emergency use as soon as September, one of the countrys top health officials said.
Gao Fu, head of the Chinese Center for Disease Control, told state-run media that the country could have a vaccine available in time for a potential second wave of outbreaks, the South China Morning Post reports.
We are in the frontline for the vaccine development, and we may have a vaccine ready for emergency use by September, Gao told China Global Television Network.
These newly developed vaccines, which are still under phase two or phase three clinical trials, could be used for some special groups of people, for example, health care workers.
Gao added that Chinese scientists may also have a vaccine for the healthy population early next year.
His statement marked the first time a Chinese official has set a time frame for the development of a COVID-19 inoculation, according to the paper.
The US Food and Drug Administration has said the release of a vaccine in the US is likely at least a year away while the World Health Organization estimated that it will take up to 18 months.
The mumps vaccine considered the fastest vaccine ever approved took four years to go from development stages to licensing in 1967, according to National Geographic.
A vaccine is considered the key to slowing the spread of the coronavirus, which has infected more than 2.7 million people and killed at least 195,000 people worldwide so far, according to Johns Hopkins University data.
An idea that might seem outlandish at first is gaining some ground as a way to speed development of a coronavirus vaccine: intentionally infecting people with the virus as part of a trial.
The idea, known as a challenge trial, would deliberately infect a few hundred young, healthy volunteers, who were first given either the potential vaccine or a placebo.Those pickedwould be well informed about the risks.
That would allow the effectiveness of a vaccine to be determined faster than a traditional clinical trial, which would require that researchers wait for some of the participants to become infected in the course of their daily lives.
Supporters say the challenge trial could save several months in the search fora vaccine, which is widely seen as critical for people to feel confident again with social gatherings.
A group of 35 House lawmakers, led by Reps. Bill FosterGeorge (Bill) William FosterControversial idea to speed coronavirus vaccine gains ground Illinois governor endorses Biden one day before primary Durbin endorses Biden: He 'can start to heal the wounds of this divided nation' MORE (D-Ill.) and Donna ShalalaDonna Edna ShalalaDemocrats roll out national plan to reopen America Watchdog group files ethics complaint against Rep. Shalala Controversial idea to speed coronavirus vaccine gains ground MORE (D-Fla.), a former secretary of Health and Human Services, wrote to the Food and Drug Administration this week lending their support to the idea.
Our situation in this pandemic is analogous to war, in which there is a long tradition of volunteers risking their health and lives on dangerous missions for which they understand the risks and are willing to do so in order to help save the lives of others, they wrote in the letter.
Stanley Plotkin, a renowned vaccinologist who helped invent the rubella vaccine, also endorsed the idea in an article in the journal Vaccine, along with Arthur Caplan, a bioethicist at New York University.
They wrote that the vaccine trial process normally takes months to years, during which [coronavirus] will infect and possibly kill millions. Acceleration of that standard process is necessary.
Older people have been among the biggest casualties of the coronavirus globally, while younger people have generally shown a higher chance of recovery.
Still, theidea of purposefully infecting people with a potentially deadly virus raises some obvious ethical objections.
In a statement to The Hill on Thursday, FDA spokesman Michael Felberbaum said the agency is exploring all possible options to advance a coronavirus vaccine, but also raised a note of skepticism about human challenge trials, pointing to testing in animals as a possible alternative.
The FDA is exploring all possible options to most efficiently advance the development of safe and effective vaccines that will prevent COVID-19, Felberbaum said, while adding thathuman challenge studies used to develop a COVID-19 vaccine may present ethical and feasibility issues that can be avoided with the use of animal models.
Jeffrey Kahn, director of the Johns Hopkins Berman Institute of Bioethics, said he did not see how an institutional review board that oversees researchwould approve a human challenge trial for the coronavirus.
Consent can only do so much work, he said, raising the hypothetical of whether it would be ethical to take out someones heart and replace it with an experimental device simply because the person consented.
Challenge trials have been conductedin the past, but they are usually done to test vaccines for diseases that can be cured, like malaria.
It would be a sharp break from precedent to do a challenge trial for a virus with no known cure that is as deadly as the coronavirus. Even if the volunteers were all young and healthy, that would not entirely reduce the risk of serious illness.
Despite the risks, experts in support of the idea said they had already heard from people willing to volunteer.
A website set up to recruit volunteers, called 1 Day Sooner, says it has already had more than2,000 people sign up.
People volunteer for the military, they volunteer to become emergency medical technicians, said Marc Lipsitch, a professor of epidemiology at Harvard University who co-wrote an article in the Journal of Infectious Diseases in support of the idea. All of those carry medical risks for the benefit of someone else and people do it.
Foster, the lawmaker who helped lead the supportive letter, said in an interview on Tuesday that he hoped the message from lawmakers would help the FDA realize that there is understanding from Congress that somewhat more risks need to be taken to develop a vaccine faster.
We should move the risk benefit optimization a little in favor of more rapid and riskier vaccine approval, he said.
If a vaccine can be ready even a month earlier, he added, then there will be tens of thousands of people whose lives have been saved.
Pressure to create a coronavirus vaccine is increasing by the day, but for a safe vaccine to enter the market, it takes time. USA TODAY
Nearly one-third of Americans believe a vaccine already exists topreventcoronavirus infection but isbeing withheld from the public, while nearlyhalf believe the COVID-19 virus was created in a lab.
As the coronavirus pandemic nears 50,000 deaths in the U.S. around half don't believe that figure either new data suggests many Americans hold misinformation about thevirus. It signals their mistrust in institutions ascitizens are being asked to rely ongovernment, health and other leaders amid the outbreak.
Twenty-nine percent saidit's either probably or definitely true that a vaccine that prevents coronavirus infection exists and is being withheld, according to theDemocracy Fund + UCLA Nationscape Project with USA TODAY.An even greater percentage, 32%, said they believetreatment that cures coronavirusinfection exists but is being withheld. Around 7out of 10 Americans said those statements are untrue.
"To see about a third of people give that some level of, 'Yeah, that might be true,' that was pretty shocking to me," said Robert Griffin, research director for the Democracy Fund Voter Study Group. "That's a pretty dark type of thought to be floating around the public. There's an undercurrent of a lack of trust in society, a lack of trust in elites."
He added: "You could sort of see how that could suggest sort of a rather nefarious bit of actions on the part of a wide variety of actors within society if people are truly holding onto that idea."
More: More people change their behavior during coronavirus as concern ticks up, survey says
The Democracy Fund + UCLA Nationscape Project, with USA TODAY, is a large-scale study of the American electorate. Throughout the 2020 election cycle, the researchers aim to conduct 500,000 interviews about policies and the presidential candidates.
The latest survey a sample of more than 6,300 Americans taken April 2 to8came as most of the country was approachingone month into stay-at-home orders and before anti-quarantine rallies started popping up at state capitals. Results have a margin of error of 2.2 percentage points. The project intends to trackresponses oncoronavirus misinformation over time.
"There's a variety of battlegrounds in a public health crisis like this," Griffin said, pointing toon-the-ground logistics and unexpected problems that arise. "But another one is just how to convince people of the truth about a variety of things."
Views on the existence of a vaccine are virtually the same among Democrats and Republicans.
No vaccines or treatments areapproved for COVID-19.Volunteers in Seattle who got shots in the first trial of a possible coronavirus vaccine are now getting the second shot an indicator the early trial is progressing well. But health experts have said a vaccine could be 12 to 18 months away, and even that timeframe could be ambitious.
In terms of treatment, Trump has repeatedly touted the potential ofhydroxychloroquine to treat the virus. But Dr. Anthony Fauci,director of the National Institute of Allergy and Infectious Diseases, has said its effectiveness is inconclusive.
More: 'He's answered that question.' Trump interrupts when reporter asks Fauci about hydroxychloroquine
The survey found 44% of Americans believe the coronavirus was probably created in a a labwhile 56% said this is likely or definitely untrue. Fifty percent of Republicans surveyed said they believe coronavirus was created in a lab compared with 37% of Democrats who said they believed that.
"The key word there is 'created,' Griffin said. "It is a question that points toward intentionality."
The World Health Organization this week said there's no evidence to support the idea that the coronavirus was created in a lab and that it was "probable, likely that the virus is of animal origin."
More: WHO says coronavirus came from an animal and was not made in a lab
President Donald Trump, who has condemned WHO and vowed to pull funding, said the U.S. is investigatingwhetherthe novelcoronavirusbegan spreading after an accident at a Chinese high-security biomedicallaboratory in Wuhan.
Forty-eight percent of Americans said the U.S. is "concealing" the number of coronavirus deaths a sentiment that's more prevalent among Democrats. More than half of Democrats, 55%, said it's probably or definitely true that the number of deaths is being concealed while 38% of Republicans said it is likely so.
Despite survey results that show mistrust, theDemocracy Fund + UCLA Nationscape Project has found that the public is generally following social distancing measures recommended by experts.
Eighty-one percent of Americans saidthey have not left their home for a prolonged period of time, a 9-percentage point jump compared with 72% two weeks before.
"Not all of this is necessarily conspiracy-thinking," Griffin said of the misinformation the survey explored."Some of it might just might purely bemisunderstanding or things that people don't know yet, a lack of education."
Other new survey findings include:
Follow Joey Garrison on Twitter @joeygarrison.
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Bill Gates, who has been warning for years of a global disease outbreak, said that while many countries have coordinated testing on a national level during the coronavirus pandemic, the United States has not, and access to tests is "chaotic."
Gates also said in his interview with Savannah Guthrie that aired on the "TODAY" show Friday that he has recently seen evidence that a hoped-for timeline of 18 to 24 months for a coronavirus vaccine may come to pass.
"Usually a vaccine takes over five years because you have many steps," including first testing in animals, then with humans on small, medium and large scales. But with the coronavirus pandemic, "because of all the incredibly negative effects, the sooner the better."
Download the NBC News app for full coverage of the coronavirus outbreak
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"The best scientists [are] working hard on this," Gates said. "In fact, in the last few weeks I've seen signs that we may get to the optimistic side of that time projection" for a vaccine.
Gates in 2015 warned that "if anything kills over 10 million people in the next few decades, it's most likely to be a highly infectious virus rather than a war."
On Friday, he called the coronavirus crisis "a nightmare," saying that "the human-to-human respiratory spread is the scariest scenario."
"I wish it had come, you know, five or 10 years later, then governments might have done the preparation to move quickly, like a few governments did," Gates said.
"Many countries decided that at the national level, they would orchestrate the testing" for the virus, he said. "That hasn't happened in the United States. It might not happen. But, you know, the access to tests is just, you know, chaotic."
Medical experts say mass testing is key before the U.S. can reopen.
Asked what he thinks about moves toward reopening by some states such as Georgia, Gates said he is "afraid we'll have some people and some states that move too quickly and have to back off."
"It's going to be awhile before things go back to normal," Gates said. "I wish I could say that we're halfway through, but I don't think so."
Elisha Fieldstadt is a breaking news reporter for NBC News.
Theres plenty of news on the coronavirus vaccine front, so lets have a look. If you need some details on the different sorts of vaccines in general, heres the background post, which should help this one make sense. This is a rapidly advancing field, with a huge number of programs. Some of the players are doing a lot more than theyre talking about, while others (as is always the case) are talking much more loudly than their actions really justify. The signal/noise isnt great, but this will be an attempt to make sense of the landscape as of today.
Update:I should put in the links to the larger vaccine lists, as I did in the earlier post. Heres a good overview of the coronavirus vaccine world in a recentNature Reviews Drug Discovery. The official WHO list is here, and at BioCentury they have constantly updated open-access summaries of the vaccines and other therapies that are in the clinic and the ones that are still preclinical. Theyve also recently published this excellent overview of vaccine issues in this area.
CanSinos Ad5-nCov
Probably the most advanced candidate at the moment is CanSino BiosAd5-nCoV. This one has completed Phase I studies and the company has apparently started enrolling patients for a Phase II trial, making them the first to do that, to my knowledge. That one is of the kind mentioned in the background post under DNA vaccines, because what its doing is using a different virus entirely (adenovirus, which infects human cells readily) to deliver the DNA for a coronavirus protein (or proteins). You can also look at this as a hybrid of live virus and recombinant protein approaches, because you have a real infectious virus (just not the one causing the disease) being used to generate protein antigens that will call up antibodies to the real disease virus. Heres a review of the approach (open access), which has had a lot of work put into it over the years. Adenovirus vector vaccines of various sorts have gone into human trials for HIV, influenza, Ebola, tuberculosis, and malaria, but none have made it all the way through yet. Thats partly because those are some damned hard immunization targets people have been trying to come up with a decent tuberculosis vaccine since before any of us were alive but that also tells you how seriously people take this technique. There are vaccines that use this different-DNA-in-another-virus technique (such as the MerckEbola vaccine) but Im not aware of any adenovirus vector vaccines that have been approved anywhere for human use yet. CanSino has an adenovirus-vector Ebola vaccine of its own (Ad5-EBOV) thats already in Phase II trials; work on that one surely provided the boost needed for the company to advance this candidate so quickly.
No one outside CanSino has seen the Phase I results, and the main thing that we know about the Phase II trial is that the company is planning to enroll 500 patients in Wuhan, and that the highest dose from the Phase I protocol has been dropped. 250 people will get the Phase I middle dose, 125 will get the low dose, and 125 will get a placebo injection. Were likely not going to hear much about this until the conclusion of the trial; any sudden news before then has a better chance of being bad.
The Oxford vaccine,ChAdOx1-nCov19
Meanwhile, Oxford University has its own candidate, which is in a very aggressive clinical development program. Theyre telescoping Phase I safety and dosing and Phase II efficacy measurements into one 510-patient trial, with numerous endpoints. This one is another adenovirus vector which will set off production of the coronavirus Spike protein and (one hopes) raise a vigorous antibody response to it. The vector is a chimpanzee adenovirus from Vaccitech, so although the concept is similar to the CanSino vaccine, this will be a different beast. There is literally no way to know which of these competing efforts will yield a better vaccine, or if either will work at all: thats why we dose human beings, and in this case those humans are (I believe) beginning to be dosed right now (Thursday!) Oxford is definitely taking a chance with their trial design, but then, everyone else is taking chances of one kind or another here.
The good news is that the Oxford group had also put work into developing a MERS vaccine (yet another coronavirus) using this same platform. Their ChAdOx-MERS vaccine also expressed that viruss spike protein, and in Phase I human trials there were no safety problems, and they did indeed elicit the desired immune response. The group has a new preprint out that shows that a dose of vaccine in animals (up to monkeys) also provided immunity against a whole suite of known MERS mutational strains, which is good to see as well. (For more on this vaccine, see the Sinovac section below).
Modernas mRNA1273
This is another one thats progressing rapidly in the clinic, and if youre keeping score, is the most advanced vaccine candidate from a US company. Modernas expertise is in messenger RNA-based therapies, and this one is indeed an mRNA vaccine, developed in collaboration with the NIH. The hope is that this engineered RNA will enter cells and make them produce coronavirus spike proteins, which will then set off an immune response. As mentioned in the background post, this is a relatively new vaccine technology, and no vaccines have been approved yet using it. It has the advantage of being fast, though, which is why this candidate is in the position it is.
Volunteers have already been given a low dose of the vaccine in a 45-patient Phase I trial in Seattle, and a larger one is enrolling at Emory, dosing 25, 100, and 250 micrograms of the mRNA in various age groups. That will set up the dosing protocols for the first Phase II trials, which Modernas management has been saying could begin in the spring. Of course, spring is a flexible concept! This is a big bet on a new technology the company has set up to receive as much as $483 million from HHSs BARDA to ramp up clinical work and manufacturing in an effort to not miss a beat should the vaccine show promising data.
BioNTech and Pfizer
More mRNA candidates are moving along briskly as well. BioNTech has a deal with Fudan to work on such coronavirus vaccines in China, and they signed up last month with Pfizer for the rest of the world. (The companies had already been working on an mRNA influenza vaccine). Word has just come that the companies have received clearance from German regulatory authorities to start a Phase I/II trial. Theyre spreading out the risk by adding to the work, taking four different candidates into the clinic more or less simultaneously.
Theyre varying both the payload and the method of delivering it. Two of the candidates use mRNAs with naturally occurring (but less common)modified nucleoside bases in them (presumably things like pseudouridine), a trick thats been tried over the years to increase stability and to cut down on the problem of developing antibodies to the mRNA vaccine itself (rather than to the protein it eventually produces!) The third has another modification, uridine-containing mRNA (presumably an extra tail of U residues?), which has been shown in some cases to increase the immune response to the protein product. And the fourth is a so-called self-amplifying mRNA, which has a sequence for a replicase enzyme in it as well. When this gets translated into protein, the replicase goes to work making more copies of the mRNA, including some double-stranded species that prime the immune system even more. As for the payload, two of these have the Spike protein (a popular choice, and for good reason), while the other two have just the receptor-binding domain from the spike (which came up in a recent post on coronavirus mutations here as well).
The trial will be dose-escalation design (1 to 100 micrograms), doing the usual range-finding for the later trials in up to 200 volunteers. Theyre also going to look at the effect of repeat vaccinations and will try some cohorts of higher-risk patients as well. This is an ambitious program indeed.
Sinovacs PiCoVacc
Meanwhile, back in China, Sinovac has received approval for human testing of an inactivated-virus vaccine (see that background post for more on these). You may recall that these sorts of vaccines often need an adjuvant to boost the immune response, since they can be less like a real infection as far as the body is concerned, and Sinovac has just recently partnered with US-based Dynavax. They have an adjuvant that theyve used in their own hepatitis B vaccine, and theyre bringing that in for Sinovac.
Sinovac themselves made news this week with a preprint that shows evidence that their vaccine produced neutralizing antibodies in mice, rats, and rhesus monkeys. The latter animals were significantly protected against challenge with the coronavirus itself, which successfully infected the control animals in what is a first report of a possible animal model in primates. Moreover, these antibodies appear to be effective against ten different mutational forms of the virus, which is good news in light of recent news about variant strains.
Perhaps the biggest news is that the company saw no evidence of antibody-dependent enhancement (ADE). This is an extremely annoying effect in which some of antibodies raised by a potential vaccine can actually be beneficial to the virus upon infection, helping it to enter cells such as monocytes and lymphocytes. ADE can be hard to get a handle on; it can depend on the antigen, the antibody titer induced in the patient, what the next viral pathogen is, etc. Indeed, its possible that antibodies to other coronaviruses might be helping the current one along in some people due to this effect. This was a major problem with attempted vaccination against dengue that virus comes in several closely related varieties, and it turned out that immunization against one could make subsequent infection with another one even worse. Its exactly what you dont want from a vaccine, and the only way to know if its happening is to try it and see.
ADE was seen in some SARS vaccine attempts, unfortunately, where its worth noting that those blood cell lines just mentioned dont even have the now-famous ACE2 protein on their surfaces at all (the virus enters through another pathway, perhaps complement receptors). There is a report of an inactivated-virus SARS vaccine that did not show ADE, though, and in the animal studies mentioned up in the section on the Oxford MERS vaccine, they didnt see this effect, either. And now it appears that this new nCov-19 vaccine doesnt have obvious ADE, which is good news.
The Wuhan Institute For Biological Products
This vaccine candidate was given the go-ahead for human trials at the same time as the SinoVac one, but its not easy to find any information about it. All I know at the moment is that its another inactivated-virus one, so it will be interesting to see what differences might show up between it and the SinoVac effort. I have been unable to find out more about the size of the trials, etc., but if anyone has information, Ill be glad to update.
Inovios INO-4800
The Inovio candidate is a DNA vaccine, the only one Im mentioning today. Thats a broadly similar idea to the mRNA vaccine, in that youre coming into the patients cells with genetic material and trying to get to them to make the antigen proteins for you. The company has been working on this platform for several years, and like several others their earlier efforts on MERS and/or SARS have jump-started their efforts on this new coronavirus. They started dosing 40 volunteers here in the US earlier in April, moving from younger, healthier participants now to older ones, and theyre moving into similar trials in South Korea. The regulatory authorities there have set up a number of fast-track procedures for accelerated safety and toxicology approvals in cases like this, where the general vaccine platform has been into human patients before.
One of their challenges is that theyre also developing a new delivery device to administer the vaccine through the skin. They have some Gates Foundation money for that, but if theyre going to get this working on a large scale there will, youd figure, be some significant manufacturing challenges in producing both a new vaccine and a new handheld device to dose it.
Johnson & Johnson (Janssen)
Now we get to the candidates that (as yet) do not have human trials set. J&J has another adenovirus platform of their own, Ad26 (see the CanSino and Oxford entries above for more on this technique), and theyve been working on a number of vaccines with that same vector. They have signed a huge deal with HHS/BARDA to help develop this one, and what we know so far is that they have run a whole series of gene constructs through the adenovirus and selected the most immunogenic candidate for dosing in primates. The company has some pretty serious manufacturing capability, and is ready to partner with others to get up to the number of doses needed theyre targeting a billion, on a not-for-profit basis.
Their Phase I trial is not going to start until September the company explains that with the adenovirus vector that you need to get the correct seeds to grow more viral vector. The stuff makes itself, but you have to be very sure that youve picked the one that you really want, and that its stable enough to keep giving you the same material over a big manufacturing run. (This is interesting to contrast with the full-speed-ahead approach taken by CanSino and Oxford one would like to know the differences between these adenovirus platforms and whos taking on the most risk with their programs)
One big difference could be that the Ad5 vector being used by CanSino has run into some problems with immunity showing up to the vector itself. (Update: I should clarify that this is because that variety of adenovirus is one that many people are already exposed to, without any particular disease being associated with it). You obviously dont want that (see the BioNTech/Pfizer entry above for similar worries). J&J has reported that their Ad26 Ebola vaccine candidate avoids this problem, so its a potential advantage. (Update: as per that last note, this adenovirus platform and the Oxford one have the advantage of humans not being as exposed to them already).
Sanofi/GSK
And heres another Big Pharma entry. Sanofi has a vaccine platform that uses insect cells to turn out recombinant antigen proteins, and this has already been used for an approved flu vaccine. Theyre bringing this technology and (as mentioned in the earlier vaccine roundup post) combining it with GSKs adjuvant (as used in their own shingles vaccine). Such adjuvants (immune-response boosting agents) are important when youre vaccinating with specific proteins like this, because otherwise the antibodies might not reach useful levels. Theyre also working with BARDA, and the companies have stated that they plan to move into human testing in the latter part of this year (similar to J&J).
Sanofis antigen is a Spike protein as well (the logical choice, as you can see from so many people using it), and their protein production platform is said to be able to deliver hundreds of millions of doses. Manufacturing capability is already being expanded on an at-risk basis, and at-risk basis is pretty much the slogan for the vaccine effort across the whole biopharma industry.
Summary
So by my count, the biggest and most advanced programs include two inactivated virus vaccines, three different adenovirus vector vaccines, two mRNA possibilities, a DNA vaccine, and a recombinant protein. Thats a pretty good spread of mechanisms, and there are of course plenty more coming up right behind these. You cannot do the tiniest search for such information without being inundated with press releases about companies working on coronavirus vaccines not complaining here and moving on to smaller companies would make this post multiple times longer. Ill update as more news comes out and add in more companies and candidates.
Eric Ginnard - eginnard@shawmedia.com
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U.S. Rep. Bill Foster joined his Congressional colleagues this week in urging federal agencies to speed up the process to evaluate and approve a vaccine for the novel coronavirus.
Foster, D-Naperville, wrote the letter with 36 other members of Congress to the Health and Human Services secretary and the commissioner of the Food and Drug Administration, according to a news release. The legislators asked the officials to prepare to rapidly deploy a vaccine to the public once it's approved.
Every week of delay in the deployment of a vaccine to the seven billion humans on Earth will cost thousands of lives," the members wrote. "Human misery also results from the economic damage caused by COVID-19 pandemic, and by the tragic psychological impact of social isolation on humans of all ages."
The legislators argued a more rapid process is needed considering the pandemic's "enormous" costs. Once developed, they wrote, domestic production and deployment of the vaccine should be "robust."
They also explained that under the typical process, approval for a vaccine could take between 18 months and several years. Therefore, the members requested the FDA consider testing vaccines using "challenge trials" which they said experts believe could speed up the timeline.
In challenge trials, volunteers are intentionally exposed to an infectious disease to test the efficacy of a vaccine. The members added they think the trials should follow the "principle of informed consent of truly voluntary subjects."
The lesson learned from a long history of using vaccines to fight massively disruptive diseases like smallpox and Ebola is that the vaccine itself is not enough. Like a good punch line, its all about the delivery.
The smallpox vaccine was an average one with a limited supply. But small, dedicated teams implemented a winning strategy for it. They focused on rapidly identifying individuals with smallpox and then vaccinating people in their circle or ring of potential contacts, creating a cordon of immunity that kept the disease out. The same strategy was recently employed with impressive results in the fight against Ebola.
Today, all eyes are on efforts to develop a treatment to immunize people against Covid-19. And the pace of progress has been impressive. Just a few months after the disease crossed the Rubicon from bats to humans, its genetic code has been sequenced and published, diagnostic tests are available, and vaccine development is well underway. There are now many candidates at various stages in the pipeline.
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Experts predict a year or more before we have an approved vaccine. Although that can seem like an eternity to many, it would be the fastest development in history.
There are many obstacles to overcome, starting with safety tests to determine that a vaccine doesnt make the disease worse. That was a concern with a candidate developed in 2003 against severe acute respiratory syndrome (SARS), a different coronavirus. And it was an issue a few years ago with a vaccine against dengue fever.
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A vaccine also must produce sufficient protection in older populations, given the age-related deterioration of the immune system, called immune senescence.
But the focus on the therapy itself can obscure complicated issues surrounding its delivery. They will be equally decisive in determining whether a vaccine can vanquish this virus.
For example, it is currently unclear how many doses will be needed to fight a disease that will have already expanded into most of the human population. The number of people who have developed natural immunity by the time vaccines arrive will determine whether we need millions or billions of doses. Rapidly producing billions of doses vastly exceeds current vaccine production capacity and would likely require costly repurposing of other facilities, or building even more expensive new manufacturing plants. Yet uncertainty about demand can make it difficult to secure sufficient investment at a fair price per dose.
Although hundreds of millions of dollars for vaccine development have already have been promised through the combined efforts of the Coalition for Epidemic Preparedness Innovation; Gavi, the Vaccine Alliance; and their partners at the World Health Organization, World Bank, UNICEF; and the Bill & Melinda Gates Foundation, the investment needed for vaccine development is $2 billion.
But investors, companies, and governments need to be assured that we will get it right that we wont underproduce and fall short of what we need, but also wont over produce and waste this unparalleled investment. When a vaccine became available for the 2009 H1N1 influenza pandemic, the outbreak had ended and many doses were simply discarded.
Even if we get the vaccine we need, we mustnt fail to get it to the people who need it. We are facing a potential shortage of health care workers to manage mass vaccination efforts, and risk increasing disease transmission by asking people to come for Covid-19 vaccination. If there are not enough doses for everyone, deciding who should get vaccinated within and across countries will need to be prioritized; although this may be a function of whether the vaccine works well enough in particular populations, such as older adults.
Communication around the vaccines efficacy and safety need to be carefully planned and monitored so as not fuel mistrust in a novel vaccine.
All of these challenges present an opportunity for innovation, including creating vaccine formulations that dont require refrigeration and, better yet, are needle-free. Several years ago, the MenAfriVac meningitis vaccine was rapidly deployed to great effect in the Sahel region of Africa, in part because it could remain stable for several days without refrigeration. If we get started now, it might even be possible to develop a skin patch that could be sent through the mail and self-administered. Thinking about new ways of delivery and who can administer vaccines could help change the game.
All of these issues can be addressed, but the work must start immediately, not the day the vaccine is licensed. The keys are to:
The novel coronavirus is not the most aggressive pathogen that disease fighters have ever faced. But its fast and elusive. Our strategy for fighting it must be as novel, agile, and global as the virus itself. The battle starts in the lab, but it will be won or lost in the delivery.
Lois Privor-Dumm is the director of policy, advocacy, and communications, and director of adult vaccines, for the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health. Naor Bar-Zeev, Ph.D., is the centers deputy director and director of epidemiology. Maria Deloria Knoll, Ph.D., is the centers associate director for science.
