Yves here. Let us hope the race to get a Covid-19 vaccine out does not give anti-vaxxers new talking points.
By Ignacio Moreno Echanove, an epidemiologist
Given the hype and hysteria about Covid-19 I tried to escape for a while from the tunnel vision we are immersed and have a general vision on what is going on with vaccines for Covid 19. I want to share with you what I have come to see in a long evening.
This won’t be comprehensive but an overall view with a critic eye on the existing possibilities with Covid-19 vaccines and their development timelines. I wonder how much matters who wins the race if there is a winner that takes it all. For instance, if the winner is the fastest but not the safest or simply the best. I also wonder as Dr. Shibo Jiang does in Nature (1, links below) if the run to deploy vaccines against Covid-19 might result in big mistakes. Jiang gives an idea of requirements to be fulfilled (direct quote from the article):
In my view, standard protocols are essential for safeguarding health. Before allowing use of a COVID-19 vaccine in humans, regulators should evaluate safety with a range of virus strains and in more than one animal model. They should also demand strong preclinical evidence that the experimental vaccines prevent infection, even though that will probably mean waiting weeks or even months for the models to become available.
He goes on to mention STANDARD GUIDELINES that should be respected and adds that many problems were found when SARS 1.0 vaccines were tried in ferrets, mice and monkeys. Developing a vaccine is not a straightforward procedure. His conclusion is: beware of hype about Covid-19 and proceed with due caution. I strongly recommend reading his letter to Nature in full. Not a long read.
The WHO provides with a document (2) that lists up to 44 vaccine candidates currently being developed for Covid-19 of which two have just initiated, in record time, clinical assays in humans. These probably prompted Mr. Jiang letter above as it seems these might have found shortcuts on their way to human assays. Interestingly, one is Chinese (3) and the other is American (4). Are both superpowers competing to demonstrate the world who is the fastest?
The other 42 candidates listed in the document are being developed by private companies (some sponsored or owned by Big Pharma firms), public institutions and public/private partnerships around the world. It is a complex landscape with many interests involved. At least one of these includes a partnership between an American and a Chinese company. I like that! La crème de la crème au monde is in search for a vaccine and one should be confident that someday in a not distant future this will result in success.
The WHO list also gives info on the technological platforms used to develop each vaccine, and in this sense, there is also wide variability: the whole existing vaccine toolbox (DNA, RNA, inactivated/attenuated virus, pseudo-virus and protein subunits of all flavours), is being tried to fight Covid-19. This is encouraging. In a few cases, the candidate uses a strategy that has been shown to work before against other respiratory virus including coronavirus. Even more encouraging! In other cases, the candidates are quite innovative with many associated unknowns.
So, it might be the case that at the end of the clinical selection procedures we have a bunch of candidates that prove protective, though we might miss the highly desirable characteristic of long-lasting protection. Successful candidates will differ on their easiness for en masse production & deployment, their levelized cost, their efficacy (degree and duration of protection), risk assessment of side effects, and very, very, few, if any, will make the final cut. Some technologies come with novel specialized inoculation instruments which imply longer and more expensive deployment time plus training.
With more than one candidate available, further selection might depend on economic interests, political influence and, critically, on the speed with which any of these gets the approval. It has occurred before that excellent vaccines arrived too late. This, again, spells that there are strong incentives including political pressure to follow shortcuts that, as Dr. Jiang states could be disastrous. Besides the Chinese and American candidates, the Head of the EU Commission has announced fast-track procedures for a German-made candidate (5). Whether this is safe is highly questionable and I wonder why some projects run the fast track while others not. [This Aussie link (5) is worth a read]
So, human trails are being started just by now and more will come in May, June, July, September… but the WHO says that they wouldn’t expect nothing to be ready until mid-2021. In China several candidates are being tested in animals and at least one is about to enter phase I of clinical trials. With some hype it has been announced that an “emergency vaccine” could be ready by April as they start clinical trials (3). This must be the CanSino Inc. (Pseudovirus or non-replicating virus) vaccine candidate listed by the WHO document. If all goes OK with this candidate, large-scale deployment would lag another year so. In line with WHO timelines. The first candidate to start human trials is from US biotech company Moderna (RNA-based vaccine) in Seattle as has been announced today (4).
In the pipeline, another candidate from Inovio Pharmaceutical Inc (DNA-based vaccine) will also start human trials in April in the US (6). To my knowledge none of these companies, including the Chinese one, has ever delivered a working vaccine before, though Invio has a MERS vaccine candidate in Phase III. When you are testing an innovative approach, special care should be taken to analyse their potential risks. Clickbait headlines announcing vaccines around the corner abound these days.
I wouldn’t like to end without mentioning the seemingly favourite EU Commission project (CureVac) that has just received 89M $ funding (7). This latest link merits a read as it highlights how inexistent the international coordination and cooperation so loudly touted in forums is. This project is, again, very innovative and to my knowledge this company has not ever delivered a commercial vaccine. Following the neoliberal playbook a few companies are being heavily financed with public + private funds and these are the first to reach clinical trials. What about some other projects managed by public institutions that have already delivered working vaccines before? Are these receiving similar support?
Conclusions: stay tuned but beware the hype and be cautious. Above all, demand strict risk assessment on vaccines before rushing for it!
(1) Don’t rush to deploy COVID-19 vaccines and drugs without sufficient safety guarantees
https://www.nature.com/articles/d41586-020-00751-9
(2) DRAFT landscape of COVID-19 candidate vaccines –20March2020.
https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf
(3) Covid-19 Vaccine May Be Ready For Emergency Use By Apr, As China Claims Research Is Going Well
https://mustsharenews.com/covid-19-vaccine/
(4) First human trial for coronavirus vaccine begins Monday in the US
https://www.cnbc.com/2020/03/16/first-human-trial-for-coronavirus-vaccine-begins-monday-in-the-us.html
(5) A coronavirus vaccine trial in humans has begun. When could a COVID-19 shot be available? https://www.abc.net.au/news/2020-03-18/coronavirus-vaccine-human-trial-covid19-immunity-hopes/12067024
(6) Which Companies Are Working On A Covid-19 Vaccine?
https://www.worldatlas.com/which-companies-are-working-on-a-covid-19-vaccine.html
(7) Curevac gets $89M funding offer from EU for COVID-19 vaccine, denies U.S. acquisition rumors
https://www.bioworld.com/articles/433728-curevac-gets-89m-funding-offer-from-eu-for-covid-19-vaccine-denies-us-acquisition-rumors
43 comments
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Thanks for this great overview Ignacio.
One question – Is it not more likely that we could end up with several vaccines, each rolled out in accordance with a risk/benefit calculation? For example, a ‘quick and dirty’ vaccine that may suitable for high risk populations such as the over 70’s, or those undergoing treatments for cancer. This could be used while one is developed for the general population where a more rigorous proof of safety is needed. Perhaps we could end up with a spectrum of vaccines from ‘its probably dangerous, but better than nothing for high risk people’, to ‘not very protective, but on a population level this could keep a cap on the disease’.
One other point about the lack of co-ordination. In the link yesterday to the Asian Boss youtube interview with Prof. Kim in Seoul, he said that one reason for the speed Korea managed to get test kits available is that SK has a range of small pharmaceutical companies that were working on this problem since the SARs outbreak, and he attributed the success to ‘capitalism at its best’ or words to that effect. I do wonder if that perhaps the approach of letting lots of countries/companies/organisations, compete with each other may be the better one given the failure so far of transnational co-ordination.
Another interesting thing Prof Kim (who is the equivalent of Dr. Fauci) said in the interview was that we could expect it to take many years (as much as a decade) to develop a very effective vaccine (30:20 in video).
If these vaccine efforts follow the norm then ‘herd’ immunity will be the default solution – with all of that’s fallout economically and socially.
Thanks again for your contributions, Ignacio.
One thing that Michael Osterholm mentioned in his interview on the Joe Rogan Experience a few weeks ago was Anti-body Dependent Enhancement (ADE), which if I understood correctly means that an unsuitably well-tested vaccine could wind up making infections worse rather than effectively warding them off. I was expecting to see the term in more news articles but a quick search doesn’t result in too many hits. Is this the sort of thing that would immediately be screened out in clinical trials? Or does it require a certain sample size?
A link from NC yesterday sent me to Peter Kolchinsky’s twitter feed where he discusses why variolation is a bad idea, but I’m afraid that leaders will be looking for magic healing trinkets or other plausible-sounding ideas in a few more weeks.
These are the kind of things to be tested first in animal models then in humans. The sample size increases in the different phases of the trials.
I did not see this episode of the Joe Rogan Experience, but what does “an unsuitably well-tested vaccine” mean as opposed to “a well-tested vaccine”? Are you saying that there have been some vaccines that have made infections “worse rather than effectively warding them off.”
Also, who is Michael Osterholm? He seems to be one of the “anti-vaxxers” that Yves was referring to when she wrote in the intro: “Let us hope the race to get a Covid-19 vaccine out does not give anti-vaxxers new talking points”?
Also, Peter Kochinsky seems to be an “anti-vaxxer”? “Variolation” is archaic for vaccination.
> some vaccines that have made infections “worse rather than effectively warding them off
There are instances in which vaccines have induced immune responses that made clinical outcomes worse in some vaccinated patients than in unvaccinated. A NC commenter has been warning about this possibility for a number of weeks.
This item seems important (I think I may have seen it linked at NC in the last day or two; not sure — time is telescoping for me and it’s hard to remember where I read things that I have seen very recently)
https://www.pnas.org/content/early/2020/03/27/2005456117
Michael Osterholm, Director of the Center for Infectious Disease Research and Policy at the University of Minnesota
Definitely not an anti-vaxxer.
The old saying haste makes waste is appropriate in this case. A fear I have is that products will be developed and allowed to be sold that aren’t effective.Two big items will be ventilators and a vaccine. Defective products will appear and they could harm or kill people. At 78 I’m old enough to see this happen. I’ve tossed around in my mind whether I would be vaccinated when one appears. I’m still undecided because I’v seen too many harmful products being allowed to be marketed. I read an article that the ventilators that CA received from Washington were all broken. It’s a good thing that the state tested them before distributing them. The governor said nothing but sent them to be repaired. He didn’t want to deal with Trumps bullying. Unfortunately we have a so called leader that can’t lead. He is so wrapped up in himself that he only wants praise. This will and has already resulted in people unnecessarily dyeing.
“This will and has already resulted in people unnecessarily dyeing.” Do you mean Trump’s hair?
Sorry could not resist.
Thanks for this. Hope this isn’t changing the subject: this NYT article yesterday suggested that all medical expenses related to the pandemic be covered by the government:
https://www.nytimes.com/2020/03/30/opinion/coronavirus-economy-saez-zucman.html?fbclid=IwAR2Q9pw6dbKru_8UiHmNR42Qp8e-Xb3E5Rh9g_DnFTRq8O8Tg10ZDHv14zQ
This would (hopefully) put a ceiling on profteering. ???
I read that developing a vaccine to mass production and deployment can cost about 500-700M $. Most of these 44 candidates will stop well before in different phases but given the cost of Covid 19 epidemics, the cost/benefit ratio of a successful vaccine might be very low. Governments/institutions are indeed pouring money and resources on this. I didn’ say anything about treatments but after some crazied let’s try this or that but without testing the real quantitative/qualitative benefits of the treatments, hospitals are now massively participating in true clinical trials.
@Hank Linderman
March 31, 2020 at 7:29 am
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“This would (hopefully) put a ceiling on profteering. ???”
Not likely. The predatory capitalists see the government as their prime *mark*. They know that the federal government can pay whatever price they want to charge if the product or service is important enough.
Neither Congress nor the administration has any incentive to bargain for a better price. Markets, y’know.
(This was a reply for PK above)
If when you say ‘quick and dirty’ dirty means not very good, provides protection though not as high as desired, but it is very safe, I would say yes. We don’t want more complications for people at high risk.
The main advantage in SK, was that they have had recent experience before. I think that having different options is excellent but cooperation, sharing common infrastructures for different candidates, would help in the rush for a vaccine and might result in less expenses. If during the process you can have direct comparisons between different candidates (coordination) it would help to discard faster those that are less promising.
Until a vaccine is developed, why not use each individuals immune system — obviously limited to those with good immune systems — to allow the body to develop its own internal “vaccine”? One variable in how severe the infection becomes is the viral load that causes the sickness. If scientists could calculate the ideal viral load — too low would not trigger an immune system reaction, and too large and it may overwhelm a healthy immune system — then during this lockdown people who were able to isolate from immune compromised people could intentionally get infected. If all goes as planned, fourteen days later, upon recovery, these people would have strong immunity to the virus. This would be particularly important for health care workers who presumably are getting exposed to large viral loads and some younger, healthy nurses and doctors are succumbing to the virus. There is probably also, even after recovery, a limit to how much of a viral load a recovered person could take but that would be much higher than the viral load that could kill a healthy person without immunity.
This is what I was referencing in my comment above, variolation. Here is a thread from Peter Kolchinsky about it:
Given that I’m in my early 30s and don’t have any known immune issues, I wouldn’t be opposed to a roll of the dice on this glancing at initial estimates of hospitalization rates by age group. Although entertaining being a voluntary “early adopter” for a new respiratory disease with unknown long-term effects and a plausible path to a vaccine probably means I’m more than a bit daft.
What load could be considered ‘safe’ to inoculate to how many people and avoiding too many hospitalizations? Nobody wants to try that experiment. Controlling biological things is not that easy.
Indeed. And, crucially, we still have no idea how long the antibodies last. We do not have long-term immunity to the other coronavidae such as say OC43 to my knowledge (happy to be corrected).
Presumably the antibodies would last around a year but it is true no one knows for how long. The point is not to replace the eventual vaccine, but instead the have a sort of bridge to get from today to the vaccine in the best shape possible. 70% to 80% of the people are going to get it anyway, why not figure out how to give it to them in a way that gives them the best possibility of surviving?
People are willing to be tested for vaccines. More to the point, young people are having “Corona Parties” where they infect themselves intentionally with Corona. Some of these kids end up getting very sick because they overdo it at these parties and presumably the viral load is way too high. So it is not at all true that “nobody wants to try that experiment”. Kids are themselves attempting this experiment, in a very dangerous way, all across the country. With scientists leading these experiments they could err on the low side of the viral load until people do have a reaction.
Is it not unethical to exploit people’s foolhardiness, especially in such a dangerous way? The viral load necessary to successfully infect depends on more than its population; also, no doubt, on many other unknowable variables peculiar to the target, and on chance as well.
“The viral load necessary to successfully infect depends on more than its population; also, no doubt, on many other unknowable variables peculiar to the target, and on chance as well.”
Sounds like a challenge for science to figure out…
I for one am curious if we have any data yet on whether or not recent common corona virus infections have had an impact on morbidity or mortality from COVID19…
I sure hope some smart folks are looking into that
i remember reading about a group/nerd herd who was going through a bunch of already approved and safety tested drugs to see if any would work.
haven’t seen anything about it since.
and i don’t remember where i saw it.
Ignacio: I have come to find out that I have an over-abundance of T-cells. I believe that over the years this condition has provided me with some protection from bacterial and virus-like abuses. It has also led to a couple of minor physical ailments not worth mentioning. More importantly, I wonder if some sort of T-cell booster is available as an interim measure of protection against CV?
Thank you.
I don’t know much about this. But it has been shown in many cases that Covid-19 causes a significant decrease in T-Cell counts. Are these SARS CoV 2 targets? Also many problems arise when coronavirus infect the lungs and elicit highly inflammatory immune responses that make things worse. This is a complicated subject well above my pay grade. No easy solution available so far I guess.
overabundance of T-cells can kill you. A lot of auto-immune diseases are in reality the immune system going into unchecked overdrive. I’d not recommend to anyone to change their immune system balance w/o at least some consultation.
Agree 100%. And I speak as someone whose over-ambitious immune system (genetic causes are implicated but not confirmed as environmental factor are also thought to play a part) has already shredded one cornea, necessitating a transplant which is neither pleasant not risk-free and has a long recovery time and may have to have the other cornea treated the same way.
There is a great deal about immune responsiveness which we do not fully understand. The number of people I see apparently quite happy to try have-a-go “cures” based on gut-feel, limited research, “horse sense” and what some guy on the internet sez is shocking.
*If you want medical advice, consult a clinician*
Ignacio is well qualified and speaks from a position of great expertise. Please follow his words of wisdom everyone in his comment above @ 10:32
What about vitamin C? China is performing clinical tests. Orthomolecular Medicine ala Linus Pauling is good place to look. Too cheap for our researchers. Not enough profit in vitamin C, and China produces most of it.
The fact that this virus mutates very slowly gives me hope that any vaccine developed can put paid to Coronavirus once and for all. But what does concern me is what happens if one is found and who finds it. Trump tried to make an exclusive offer on a German drug so that only the US got it. But what happens if China gets one first. Or Russia? Or even a country like Iran? Will there be a power play here? And if a corporation develops it, will they ask for something like $50,000 a dose – in contrast with Salk’s polio vaccine? Who will get it and will people be able to get it?
Good article by the way Ignacio. Make sure to keep your head down where you live. Spain is really copping a flogging at the moment unfortunately.
it’s reverse engineerable, so worst comes to worst, the IP laws will be bent (most of them allow for requisitioning during crisis anyways). Also, with the number of vaccine candidates, it’s likely that more than one will succeed.
TBH, I’m most worried for US here (and the UK who’s moving to the US orbit), as they could become another rent extraction from the poor.
I’ve read there are already at least two strains of the COVID-19 virus. I believe the author suggested that it might mutate more quickly than expected. Do you have a source for “this virus mutates very slowly”? What are the implications for developing a vaccine if it does mutate rapidly?
Can someone recommend a good “Viruses for Dummies”? A search of Amazon suggests there isn’t anything that specific. I have nothing against picking up a little microbiology if necessary.
P.S. A Japanese woman has apparently been infected twice.
You can follow the corona virus evolution as it is being sequenced here : nextstrain.org
Nextstrain is an open-source project to harness the scientific and public health potential of pathogen genome data. We provide a continually-updated view of publicly available data alongside powerful analytic and visualization tools for use by the community. Our goal is to aid epidemiological understanding and improve outbreak response.
Awesome website. Thx for the link
I’ve got to add my voice to all those who say “Thank you”, Ignacio. My science is physics so there is so much about biology and biological processes that I just do not get and I am often confused by what I read online – and the many stories that seem to conflict. I appreciate your common sense approach and your ability to explain these concepts in a way that I can understand! I actually look forward to your articles!
I am just a layman but everything I’ve read — other than business hype — suggests a corona vaccine will take a long time to develop. In my opinion, it is far more important to review the not so standard guidelines for how to handle a pandemic — the more mundane methods used to quarantine, care for the sick, and protect the public in public spaces. My impressions from what I’ve read also suggest to me that there must be much more basic research on viruses, how they spread, where and how they survive in our environment. Consider the controversy over face masks.
Several changes to FDA STANDARD PROCEDURES scattered through roughly pages 415-510 of the CARES Act could make trying out the new vaccines or corona drugs a risky business — although I didn’t scan much of this portion of the CARES Act and many of the changes are described in ways I could not easily understand. I suspect these changes reflect long-time wishes of Big Pharma kept on the shelf waiting for an opportune moment.
I fear the rush to find a vaccine will beggar the limited basic research that will be done. I am also concerned that the corona virus is just one of many pandemic viruses we can expect in the future. Developing better standard guidelines and practices for dealing with future pandemics is much more important than racing around developing a vaccine for the corona virus.
Great point. BAsic public health measures like M4A, housing for all, Finacial supports for all!
And we NOW
Handwashing, social distancing , staying at home when sick, respiratory etiquette
But also hotels for infected, hotels for HCWs
Why is it faster to make a vaccine for Covid 19 than viruses also disabling and lethal like HIV, Herpes 2 (or 8), Hepatitis C, etc?
Malaria, though a microbial disease, we are nowhere near a vaccine.
Heck, Polio is still out there.
I just don’t understand the optimism that we will get this.
(hi Jules, I think I should change my screen name or mail address because I always get sent to moderation)
Malaria is caused by a parasite, which is not a bacteria or a virus but more like our own cells, which is why it is difficult to treat.
HIV attacks some cells of our immune system, which is why it is problematical. It is, as it’s name suggests, a virus and a retrovirus as is Coronavirus. They have RNA rather than DNA as their genetic material but once that RNA has entered a mammalian cell it has to be copied into DNA to drive the synthesis of new viral proteins and RNA to replicate the virus. RNA to DNA needs an enzyme we don’t have but the virus does, reverse transcriptase. So reverse transcriptase is a target for anti-HIV drugs. Hence the interest in reverse transcriptase inhibitors developed for HIV and Ebola to treat COVID-19 patients.
“further selection might depend on economic interests, political influence ”
might as in might makes right
Ignacio: how can you be reached?
Via Yves, if she accepts that! She can redirect me emails.
Thanks Ignacio for the review.
I think that, while the possibility of developing a vaccination should be one of the top priorities in the effort to eradicate the disease, I wonder whether a more timely way to get the workforce employed again is in massively scaling up testing – both for the antigen and antibodies. I can imagine that if both tests were widely available and affordable that a kind of workforce reentry credential could be issued to people if they tested antigen negative and antibody positive – they could wear a button on their lapel signifying their safe status and thereby gain entry back at their work place or into safe establishments like restaurants and the like. It might be a good way to slowly get the economy going again.
Hi Jeff,
Ramping up of testing is the only of getting back to normal quickly. That’s how South Korea and Taiwan do it. The problem with vaccine development is that it is impossible to tell how long it will take to develop a safe and effective vaccine. We still have not developed a HIV vaccine after more than 30 years of trying. There are early indications that a number of antivirals help in curing Covid-19. For an overview see this article:
Dutch researchers also found recently that COVID-19 was detected in sewage in the city of Amersfoort weeks before the first COVID-19 case was found in that city: https://www.dw.com/en/coronavirus-in-sewage-foreshadowed-outbreak-in-dutch-city/a-52972980
Testing COVID-19 in sewage can be a very fast and affordable way of tracing COVID-19 in the population.