Speeding up a vaccine by even one month might save 100,000 lives. The U.S. once dropped bombs killing a hundred thousand innocents to curtail a war; challenge trials conducted on healthy young human volunteers entail only tiny risk compared with the potential savings of lives.
I just remember the Seventies, when it seemed like every newscaster seemed to be warning the population of impending doom via Swine Flu. It was going to be the biggest baddest worstest of all flu. The laboratories worked like crazy to develop and distribute the vaccine, and it was free. People lined up in droves to get their shots with an air gun, (OWWW!)
I can’t even remember how bad the flu season ended up being.
Years later, some people had trouble functioning, unable to perform even their own care. Nobody knew what was going on. The strange new illness was Epstein-Barr, and was apparently triggered by the Swine Flu shot.
~VOW
No, we will definitely not achieve herd immunity levels by late summer; given the infectiousness of this disease and the asymptomatic spread, I think a significant herd immunity threshold is going to be at least 60% and likely exceeding 80% to really push it down below epidemic levels. I based that guestimate on the premise that we’re going see greater infections as states open up that will start becoming apparent in June, and then a bunch of states will try locking things back down with a similar lag period to what we saw before (or perhaps a little faster as people in states that were previously less affected take it more seriously.) There is no particular reason to believe that spread of SARS-CoV-2 will be attenuated by ambient heat in the way seasonal influenza is, and while sunlight definitely does destroy exposed virus there are plenty of areas that are shadowed (on the underside of a door handle or any place inside without good ventilation) where virions can accumulate. SARS-CoV-2 is spreading just fine in subtropical and tropical countries like Brazil.
An unsafe vaccine could cost millions of lives and undermine efforts to later deploy a proven vaccine. Challenge trials (where patients are inoculated and then exposed to live virus) are ethically suspect, particularly if the virus has not first been through safety trials. The suggestion has been made here and elsewhere that volunteers from medical and front-line workers who are likely to be exposed anyway could be used in a pseudo-“challenge trial” but again a ‘bad’ vaccine could literally make this virus an order of magnitude more lethal. Let’s permit the actual experts in immunology and virology follow the decades of immunology research processes and safety protocols developed by the experience of trying and seeing what works and what doesn’t instead of trying to do an end run around sound science. And instead of depending on the “Hail Mary pass” of a quick vaccine, let’s work to find therapeutics and ways of reopening parts of our economy and society in absence of a vaccine that may not come for years or at all.
Stranger
Just want to point out that Brazil’s worst outbreak is in Sao Paulo, whose climate includes a relatively cold winter season (its autumn there right now), with the temperatures falling to below freezing somewhat regularly.
Although I have read that Manaus is also suffering and that’s equatorial.
Wuhan is about 30’N, the same latitude as Cairo, Houston, and New Orleans. It’s actually south of Baghdad, Atlanta and Islamabad. Traditionally 30N is considered the start of the temperate zone. It is the first northern latitude where seasonality becomes noticeable (as in needing heating in the winter).
You try the vaccine on some dozens of volunteers, then expose them to the virus. If the vaccine is ineffective then 1 or 2 of the volunteers may die — after all, they’re young healthy volunteers not in a high-risk group. How do you get from “1 or 2” to “millions”?
OF COURSE, you proceed in a manner condoned by policy and medical experts – you’re just changing risk priorities, as Secretary Shalala suggests.
COVID-19 arrived here in earnest in late March. The concern is that, in the Fall, it will resurface at the same time other flu and cold viruses normally resurface, so the impact will be greater because of that alone. In a few short months, all these questions will be answered.
As my dad used to say, “We shall see what we shall see.”
Sao Paulo’s coldest month is July, with an average low of 56 degrees. It’s not as cold as you’re implying.
Guillain–Barré, not Epstein-Barr. Epstein-Barr virus causes mononucleosis
Antibody-Dependent Enhancement. A vaccine that is rushed through a single limited phase of testing may not be well vetted for safety in the genral population, particularly considering that hypothetical challenge trials would likely select the “young healthy volunteers” as you note but it is older people, many of whom have underlying conditions that may aggravate their response, who are disproportionately affected. Given how poorly we understand the pathogenesis of this virus even in otherwise healthy people with very mild symptoms, rushing to deploy a virus “as fast as possible” without the kind of safeguards that immunologists have learned—sometimes by grievous error such as the 1976 H1N1 vaccine previously mentioned—could have catastrophic consequences. Even if it doesn’t result in ADE, an ineffectual vaccine may discourage compliance in future vaccination campaigns. Again, we have these testing protocols for very good reasons, not just bureaucratic ‘red tape’ to employ functionaries.
As a former Secretary of Health and Human Services, Donna Shalala has some authority in public health policy. However, her education and professional experience are in political science and law, not virology or immunology. In the question of whether the risk of challenge trials and other ethically problematic measures are necessary we should consult with the people with technical expertise in the field.
Stranger
Obviously. The point is that policy-makers need to provide inputs regarding risk assessment; medical experts may be constrained by literal adherence to the Hippocratic Oath.
Whups, sorry! :smack:
That’s what happens when I post after only one cup of coffee!
~VOW
“Some dozens” really is a bit of an understatement … but neither here nor there.
If all you who are talking about with the urge to speed it up or race it through is to approve human challenge trial with lower risk populations, well personally I think that is a fine ethical way to proceed. But realistically that bit is just one of the many steps to prove a vaccine product safe and effective across all demographics. Speedy it still likely will not be. Shave some time off maybe.
From the Financial Times Article quoted is some interesting stuff. One bit is this:
FWIW … one option for influenza immunization has been a live attenuated influenza vaccine administered as a nasal spray, brand name FluMist. It faded off in use when in one season it was not a great match against H1N1 but is approved for use again both last year and in the current season with a modified H1N1 component.
One wonders if development of a reduced virulence SARS-CoV-2 to use in a challenge would spin off a Live Attenuated SARS-CoV-2 Vaccine … although the fact that FluMist had disappointed against H1N1 may leave a developers a bit hesitant to go there. But theoretically a live attenuated vaccine is more likely to provoke a T-cell response than most of the other approaches proposed, so the temptation may still be there, given the reduced virulence bug may be half way to product.
Huh. Googling a bit comes up with this proposed approach. Interesting.
COVID isn’t the 1918 influenza virus, and I personally think we are in the “second wave” right now, due to all the people, myself included, who quite likely had it before it was officially identified.
I just hope that there’s no third wave, fourth wave, etc.
Dozens? That may do for a Phase 1 trial. It’s not close to enough to ascertain if the vaccine actually WORKS. You need a substantial clinical trial.
There’s no resistance if it has only hit 5-10% of the population. A major outbreak will easily infect two to three times that amount. Even if it’s a widespread pandemic, perhaps only a third of the global population might be exposed to it within the first year. There’s the potential to infect more. Viruses can also mutate from year to year.
The 1918 flu’s second wave was arguably the first true wave, as the initial outbreak in spring of that year was geographically confined. It didn’t become a pandemic until soldiers from the US brought it to Europe, and then brought it back to the US in the fall of that year. The spring 1919 was bad, but it accounted for only 20-30% of the entire fatalities during the entire pandemic.
The fear that people have now - in the US anyway - is that a failed public health response will allow COVID-19 to hang around until fall, which is when the flu season begins. If that happens, reopening the country would be an absolute nightmare, as would holding a regular presidential election.
Nope. Right now is the first wave - the second inning of a 9-inning baseball game. We’re a long way from being done with this, and contrary to what you may believe, the reality is that a very small percentage of the world’s population has been exposed. Probably 92-97% of the US population has not been exposed. We’re nowhere near being done with this.
If successful, it would give the confidence to proceed with bigger trials and speed up vaccine availability.
Look, you guys may be qualified to debate the details of vaccine trials, but that’s a topic on which I know nothing. I am just arguing that the usual Hippocratic Oath proscription against challenge trials should be weakened given the speed with which this virus may spread. Experts would still guide the details, but “ethical standards” — unrelated to either science or utilitarian goals — need to be reviewed if they would otherwise be likely to (hugely!) increase human suffering.
There is nothing in the modern “Lasagna version” of the Hippocratic oath that specifically proscribes or limits the ability of physicians to conduct challenge trials. I suppose you could interpret “I will prevent disease whenever I can,” as an explicit prohibition but the development of a vaccine that physicians have good confidence in is fulfilling that dictum.
The problem with rushing to challenge trials—aside from the possibility that a bad vaccine could cause the virus pathogenesis to become more virulent—is that the ethical framework for minimizing unintended mortality would drive you to select only young and healthy participants. But while COVID-19 is not only seen in the elderly and those with underlying conditions, the most severe cases are disproportionately presented in that population. A challenge trial that is successful in only a population of young and healthy individuals can really only be assured to demonstrate safety and efficacy in those populations. In the normal Phase I/II/III trials, safety is demonstrated first phase, basic efficacy and confirmation of safety in the second phase, and then efficacy in the broad spectrum of population demographics in the third phase.
And quite frankly if we had a vaccine candidate in the next few months there really isn’t any need to run a challenge trial; the infectiousness of the SARS-CoV-2 virus is such that you just need to identify uninfected candidates who are in an exposed occupation and enroll them in the study because there is a statistical likelihood of infections for medical personnel, first responders, and other public-facing workers. And if we get to the point that the population pool is saturated with previously-exposed people who are seropositive then you’ve probably achieved a certain threshold of herd immunity anyway and should now be focusing on determining how long immunity will last.
There was some discussion back when the MERS outbreak occurred about running a vaccine candidate through challenge trials specifically because of how quickly the virus burns out in person-to-person spread leaving little potential for unforced infection, and the consensus was that the risk of future outbreak achieving uncontrollable epidemic proportions was low enough that more potential harm could be done via the challenge trials than by the wild virus itself. Now, you could make the reverse argument for SARS-CoV-2–that spread is guaranteed and a working vaccine will potentially save millions of lives versus the few hundred you make risk in a well-structured challenge trial—but then that goes back to the point that if this disease is so infectious and there are so many uninfected or non-immune people out there, then you don’t actually need to run a challenge trial; you can just run a normal three phase safety and efficacy trial. Running a challenge trial provides very little if any benefit in speeding up the process.
There is another potential alternative; it would be possible to run a trial using a coronavirus with a similar enough structure—particularly in the S protein—that the vaccine would also protect from but that lacks the lethal pathogenesis of SARS-CoV-2. If such a virus existed, you could use it as a trial mechanism to test for efficacy (although obviously it wouldn’t give you safety). However, if such a virus existed, it would likely also convey some level of immunity and would be a candidate for a vaccine, provided you have enough confidence that it woudn’t be able to recombine with the real SARS-CoV-2 or a live attenuated virus vaccine (if that is what you are testing) to produce another novel pathogen.
So, pretty much any testing of vaccines (and virtually any other drug that affects the immune system or other organ functions) has ethical concerns because with any new drug there is always some potential for unforeseen harms. But the particular case in which challenge trials are really both ethically justifiable and are really necessary to significantly speed up approval are very narrow; it would essentially have to be a virus that is contagious enough to be a serious threat of epidemic spread, but not in an epidemic phase such that it is unlikely that your study population will be naturally exposed to the virus in a statistically significant quantity; or else the harms of infection are not serious enough to be of concern should the vaccine not work (in which case it is unlikely anyone would develop a vaccine).
Stranger