Blockquote[quote=“kanicbird, post:18, topic:922571”]
There is no such thing as natural herd immunity. As more people become immune from having and recovering from the disease, there is less people BECOMING immune because less are able to get it. Thus with new people entering the world all the time (and added the affects of global travel), the number of people who can catch it increases and gives the virus another chance one it gets a hold, called a second (third, etc.) wave. Herd immunity is impossible this way. This is why we had chicken pox and measles parties, to help that wave hit those who can most easily fight it off in a controlled manor (children) but at no time did we reach heard immunity till a vaccine was deployed, or is some cases (cow pox/small pox) a like virus was deployed.
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Wait, but if there were no such thing as natural herd immunity, wouldn’t holding a measles or chicken pox party be a very bad idea, because any kids who got it would keep on infecting and infecting people and there would be no natural brakes on the epidemic? It seems to me that the whole concept only works because you could assume an outbreak among a small group of kids would stay within that group of kids and not spread to more vulnerable populations, and the reason why people could make that assumption is that most adults were immune already.
What @DSeid said. Any study needs to have a measurable outcome that is likely to be statistically significant if the vaccine works.
Measuring serious infections fails because the expected number is too small. Random noise is likely to overwhelm the signal unless you have a truly enormous study. Measuring whether recipients have a positive rna test is impractical, because they’d all need to be tested regularly. Not only is that expensive for whoever runs the study, it’s expensive enough for the volunteers that it would be hard to recruit enough. Do YOU want to show up in a specific place to have your nose swabbed twice a week for months on end? Would that interfere with your job, caring for your kids, and other aspects of life?
But asking the volunteers to take their temperature every day and otherwise monitor symptoms at home is completely reasonable.
And any vaccine that reduces the incidence of moderate illness is extremely likely to reduce the incidence of serious illness and the infectiousness of the recipients. Is it certain to do those? No. But it’s likely enough that I’d want such a vaccine, if i were comfortable it were safe.
In some sense we will be running a phase four trial on much of the world. Once some vaccines are approved, millions of people will take them, and we should be able to gather data on how many develop serious illness and what happens to infection rates in cities with high and low vaccine take up, it with different vaccines used.
I expect that in four years we will have a much better vaccine than we will have “asap”.
So we know a fair bit about design considerations - the type of vaccines that are more likely to trigger ADE. I think the trials are large enough to pick up on whether a vaccine will trigger any significant ADE effect in the lower risk population that the trials are looking at. That does leave the (unlikely but real) possibility that there could be no ADE effect in lower risk patients but a significant effect in older high risk patients. Of course that’s inevitable with trials - you can’t start trials on high risk patients when you know nothing. I think once again it’s a risk-reward tradeoff with the time pressure.
Well, the definition of “infected” is quantitative, the positive/negative threshold for whatever test you are using. It’s drawing a somewhat arbitrary line where no bright line really exists, of course.
But I was responding to an incorrect assertion that the immune system cannot prevent infection but only react to it. The immune system can respond to the presence of even a single molecule of antigen. The mere presence of any small amount of pathogen does not constitute an infection. If it did, we would all be “infected” dozens of times a day, since small amounts of pathogen are ubiquitous. To call something an infection requires that the pathogen at least start replicating, with a functional definition according to some quantitative threshold in a given test. Sometimes (usually) the immune system will destroy small amounts of pathogen before this threshold is reached - and that is correctly called prevention.
And just (for general information) to complete the picture here on the adaptive immune response upon secondary exposure - after we have acquired immunological memory for a pathogen through a first infection or through vaccination - a spectrum of things can happen.
After the first infection was cleared (or after vaccination), we retain a significant number of actively circulating antibodies and/or T-cells specific to that pathogen for some time afterwards, sometimes for many years. This evolved for obvious reasons - if a pathogen is present in our community, there’s a good chance that we might be exposed to it again, and the quicker you can kill it the better. So if we are exposed for a second time, there may be enough specific antibodies or T-cells already present to neutralize it immediately and prevent a second infection. If this happens, there would almost certainly be no risk of transmission to somebody else.
Alternatively, if we encounter a pathogen for which we have immunological memory but not enough specific antibodies immediately on hand to neutralize it, we quickly start producing large quantities of these antibodies. This may take a few days, but it’s quicker than the first time around. And if the lag time is shorter than the time it takes for the pathogen to start replicating significantly, the response may still be quick enough to prevent a second infection. Under these circumstances, there would likely be little risk of transmission to somebody else.
Alternatively, our immune system may still be too slow to respond, and a second infection may take hold. But since our immune response will still likely be better and faster than the first time, our immunological memory may be sufficient to make this second infection asymptomatic, or to make the symptoms milder, and to clear the infection more quickly. We may not know we are infected. It may also make us less likely to infect other people, although it’s unlikely that there is no risk of transmission from a second infection.
The final possibility, of course, is that little or none of this happens, our immunological memory fails us, and the infection is as bad as the first one (or as bad as if we had never been vaccinated).
What out of that article or otherwise leads you to that conclusion? The closest I find is this somewhat obvious statement:
Why should we think that 15,000 lower risk subjects in each arm will produce sufficient infection events for such statistical comparisons? If my quick calculations are accurate there are maybe 400 to 500 confirmed infections expected in that population over say a 100 day period (from a study perspective optimistically, maybe a handful that are sick enough to get hospitalized, and maybe a death or two in the control arm). For this population at low risk from the disease a rate of ADE or late MISC-like reactions occurring even once every few thousand infections would be very problematic and even assuming a true infection rate ten times greater would be hard to get a true signal of until post marketing surveillance.
Lots of people over there are asking the same basic questions that I am – about what the studies’ endpoints mean, about what that will or won’t tell us about transmissibility, about how far “success” will take us toward what most would call a pre-COVID normal.
In other words, they want to know what “success --” as the industry is currently defining it – looks like.
If uptake is expected to be rather low, if vaccine efficacy is going to be modest, if it isn’t very likely to reduce transmissibility, if masks and social distancing will still be prudent for most people, then an argument could be made that – for some:
The reward may be too low to accept an unknown level of risk … immediately;
The “irresponsible and selfish” piece may be much more akin to motorcycling without a helmet than to driving drunk (ie, the former may have relatively minor costs to others, broadly, but the main harm inures to the rider. The latter, OTOH, creates risk for everybody around the driver).
So … if I’m already exercising all the precautions, and am willing to continue to do so, and if I’m not particularly compelled by the endpoints of the first round of trials … and if I’m willing to wait for my pitch, and swing when I feel it’s right for me to do so … then I’ll just have to endure the opprobrium of those who strongly disagree with my choices.
A complication rate of the order of 1 in a few thousand in low risk groups would certainly be a problem for people’s perceptions and the rate of uptake. But I’m less sure whether rationally it’s an unacceptable risk if the vaccine is effective at slowing transmission, because in our current circumstances a vaccine that slows the spread of the disease significantly has such a large benefit. A moderately effective vaccine could lower everyone’s risk of getting infected tenfold. Then a 1 in a few thousand chance of a worse infection if you get infected doesn’t look so bad even selfishly for a low risk individual; and at a population level including high risk groups looks even better.
There’s a bigger picture too, I guess. Even if we assess the risk-reward accurately and rationally, if we get unlucky it could harm all vaccination programs for decades.
Which circles back to not knowing if it will or if it does how effectively so.
The assumption that causing moderate disease to be milder means less transmission may be unwarranted. Those moderately ill are at least more likely to quarantine. What if it creates more still infected, still able to transmit, but so mildly impacted that they stay out and about unidentified?
Just to make it clear, I will be first in line for any vaccine approved by the Canadian government. I won’t expect it to be perfect. But I will continue to self-isolate until we know more. But a lot of people will observe that vaccinated people are still getting sick, even if less serious and conclude that there is no point in getting vaccinated. So it is vitally important to get the information out there of how well the vaccine works, even if it results in fewer getting vaccinated. It is important to build trust in science.
Incidentally, were I in the US, I am not certain I would be first line on account of the politicization of the FDA.
Although… thanks to the magic of the internet and the international nature of science, most of the vaccines that might be available in the US are likely to be available in other nations, as well. I think if the Canadians, or the Germans, or the Italians, or heck, the Swedes, approve a vaccine, I will feel comfortable taking it.
(I wonder if vaccines will be approved at the national level or by the EU?)
That’s pretty much my attitude. It’ll be a few years after Trump is gone before I’ll be trusting FDA again. With luck that countdown starts soon. Though to be 100% fair, the FDA has had some real problems for much longer than Trump’s been in charge, largely due to flaky legislation that prioritized quick approval of maybe-they-help drugs over waiting longer to get provable definitely-they-help drugs. And other industry-sponsored shenanigans.
Although before I glibly accept, say, the German regulator’s word for it I’d want to know how much the Germans simply took the US FDA’s word for it vs how much they decided independently.
e.g.
One of the issues that came out of the Boeing 737 MAX debacle was that by and large, every national aviation authority had just been taking the word of whoever regulates the manufacturer; in Boeings case of course, that was the US FAA.
Since that time a much more multi-lateral coordination process has been put in place and even then many authorities are reserving independent judgment. Which right they always had but seldom used. Right now today one of the obstacles to the MAX’s return to service is a slowly resolving impasse between FAA and the EU’s authority EASA over some details.
Having worked in European drug regulation for many years, I can assure you what what the FDA says has no bearing at all on the EMA assessment and approval system. And yes, these vaccines will be approved at EU rather than European national level.
The real magic of the 'Dope is that it doesn’t matter what kind of expert we need to consult, one will be along in a couple days (if not a mere couple hours) to provide the needed expertise.
If you’re interested, this tells you when use of the Centralised (ie, EU level) approval procedure is mandatory (scroll down to Scope of the centralised procedure.)
Thank you for this conversation. This seems like really important information that the public needs to be aware of for expectations to be in line with reality, but we are not getting near enough publicity about. All the talk is about getting a vaccine, but no talk about what that vaccine will and won’t actually do. The most I’ve seen is some mention of effectivity rates without clear explanation of what those numbers mean.
I guess it makes sense that the result we are looking for right now is does it reduce the severity of infection when it occurs? This seems mostly because of the time constraint. You can’t really measure reductions in infectiousness on such short time scales.
But this is a significant readjustment in thinking for what the first vaccines will and won’t do. All the talk of herd immunity and how long the vaccine conveys immunity is bullshit if what we are really measuring is “effectivity window” or some such, not actual immunity. “Good news - this gives permanent immunity to cancer. Take it, and if you get cancer, it will be slower to grow and easier to get rid of. That’s what immunity means, right?”
There should be a vaccine accessible for each person around the world and in a short period, but that’s not going to be possible in the near future so far
