Vaccine Progress
Guest Author at Angry Bear is Professor Joel Eissenberg. Dr. Joel Eissenberg is a professor of Biochemistry and Molecular Biology and is probably a good source to ask questions concerning pandemics and bringing new vaccines to market. Ask questions . . . I am sure he will answer the same as he has commented in the Comments section. He also reviewed my layman’s piece on Moderna’s mRNA. I am hoping he will contribute at Angry Bear on healthcare from time to time.
The Moderna trial has reached its enrollment goal of 30,000 subjects and at least 75% have already received both injections. This is not a challenge trial, but it is expected that many subjects in the vaccine and placebo arms will be infected and these will be tracked. Power calculations suggest that only a few dozen infections are necessary to determine whether there is a benefit to the vaccine over placebo. So far, the number of infected subjects is at or ahead of what they expected. The trial lasts two years, so there is plenty of time to collect data. There is, of course, understandable urgency to push out some vaccine ASAP.
I’m in the Moderna trial, which tests the efficacy of injecting the messenger RNA for the SARS-CoV-2 spike protein (the surface protein that gives coronaviruses their corona) directly into muscle. The protein is made in muscle cells and then (a) secreted and (b) presented to immune cells to stimulate the adaptive immune system. Technically, it is a double-blind trial, but so far, everyone in the vaccine arm experiences the short-term vaccine syndrome of headache, mild fever, muscle and joint ache after the booster. I did, and was able to get an antibody test confirming a robust response (IgG). I’ll continue to social distance and mask as before; I have no interest in testing just how effective the vaccine is or isn’t with my own body.
The big question for this and the other vaccines is how robust and durable is the protection. This could vary because of a number of factors, including virus dosage and co-morbidities, which is why the 30,000 figure was important. My co-morbidity is age (I’m 65); older folks have a less-robust immune response on average, and it is more poorly regulated. The phase I/II cohort skewed young.
One thing that is frequently overlooked in the COVID-19 pandemic is that most people who survive a frank infection have enduring pathologies after they recover from the acute phase. In this respect, COVID-19 isn’t like the flu, it’s more like polio. So it will be important not only to see whether vaccines reduce mortality, but also if they can blunt the long-term effects on lungs, vasculature, and other organs, as well as virus-induced autoimmunity.
Tony Fauci has prophesized that there will likely be a vaccine approved for emergency use by December or the first quarter of 2021, but that general vaccination of the public won’t be a thing until summer of 2021, and assuming that enough people are vaccinated (ca. 70%), some semblance of normality isn’t expected until 2022. Even then, boosters every year or two may be necessary. I agree with Fauci. Indeed, he may be optimistic.
What is becoming increasingly clear is that infection is no guarantee of long-term immunity after recovery. Herd immunity by natural infection is mass murder, and the survivors will likely have little to celebrate. Until a vaccine is vetted, maintain social distancing, minimize time of potential exposure and wear a mask indoors when others are present. The economic impact of this is severe, yes, but ignoring these practices only leads to new peaks. Be safe out there, peeps!
Thank you for this somber and concise review. As you noted, vaccines generally don’t provide complete protection and these initial vaccines are likely to be only moderately effective perhaps providing as little as 50% once you’ve had boosters. That means for us to achieve the goal of getting COVID-19 under control and eventually eliminated, we will need to continue a combination of social distancing, mask use, testing, and contact tracing
Those other approaches already provide far more substantial protection than a vaccine alone, but since adherence varies the vaccine will at least provide a consistent level of resistance to the disease. The impact of a vaccine will only be enhanced by the efforts we make today and continue to make once it is available.
https://www.npr.org/sections/health-shots/2020/09/12/911987987/a-covid-19-vaccine-may-be-only-50-effective-is-that-good-enough
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31142-9/fulltext
@MO,
” . . . these initial vaccines are likely to be only moderately effective perhaps providing as little as 50% once you’ve had boosters.”
That’s news to me. The efficacy of the Moderna vaccine in monkeys was reported out as significant, but I don’t know that it was 50%. The efficacy of the Moderna vaccine, as well as the J&J Janssen, Pfizer, Sanofi and AstraZenica vaccines is unknown, AFAIK. Where did you get your 50% figure?
The efficacies for the smallpox, MMR, rabies and tetanus vaccines are considerably higher than 50%, and I’ve seen nothing in the data so far to suspect that the COVID-19 vaccines currently in phase III will only be 50%.
As with all vaccines, their epidemiological effectiveness depends on how many people are vaccinated. Until at least 70% of the population is vaccinated, we’ll need to continue to use practices that limit contagion and attenuate business productivity.
OK, I see you got the 50% number from the NPR link. The word “may” does a lot of work in that link. I could equally well say the vaccines currently being trialed in phase III may show ≥90% efficacy and have just as much evidence.
None of the traditional vaccines works the way that the Moderna vaccine does. Drug development has a lot of similarities to trying to add a new feature to some ancient program that has been hacked and kludged by programmers of varying ability for millions of years. There is no program logic manual or documentation of any sort. The fact that the Moderna vaccine kinda sorta works and may actually work better than that is prety amazing to me.
@Kaleberg,
It “worked” in monkey challenge studies. In Phase I/II, it led to a clear antibody response. In my case, the threshold for positive in the spike protein antibody test was 1.1, and my response a month after the booster was 8.3. Of course, we don’t know how durable the response will be, which depends in part on T cell activation. And we won’t know for another month or so how effective the Moderna vaccine will be in challenge.
Of course, the vaccine isn’t a drug.
Joel:
That is what makes the mRNA interesting. It is a different approach. I am interested in it. Not sure if we should be tampering though. “In the early 1990s, scientists wondered what would happen if they manufactured pieces of viral DNA (and mRNA) and then injected them into human cells or lab animals. The hope was that the cells would take in the genetic snippets, make viral proteins, and trigger an immune response.”
@Run,
That’s precisely what appealed to me about the Moderna trial (apart from the fact that the clinic site was on the first floor of the building where I work). The mRNA makes one protein, and unlike the J&J Janssen and Pfizer vaccine, doesn’t rely on a virus to deliver that mRNA. The Sanofi vaccine is the classical approach: spike protein + adjuvant. I would have joined that trial, if it were available.
I have proof–both physiological and biochemical–that I had a robust immune response. How protective that response is is unknown. How durable it is is also unknown. I could have myself tested again in a year for my spike protein antibody titer, but that’s not interesting. What’s interesting is how I would respond, at age 66 and a year out from the booster, to a viral challenge. I hope to learn that vicariously.
Joel:
I am not a bio-chemist or a micro-biologist. I am somebody who sees patterns and is able to discern them. On a manufacturing floor I am dangerous and valuable as I can fix what ails them. With this, it is a step away from my comfort pattern zone. I understand it but I do not know enough data on the increments of it. It will take some time before it is mine to discuss with confidence.
Do not test the theorem. It is to open to mistake. Too soon to take a chance on your immune response. It may yet mutate. Let someone else test it and you can learn by it. In high school biology, we studied Mendel’s genetics. The instructor could see I was bored and I disappointed her as she lectured. There is only so much one can listen to at 14.
@Run,
I understand your boredom with basic high school Mendelian genetics (Punnet squares, Chi square statistics). I got a C in intro genetics in college, then went on to get an A in microbial genetics and a PhD in genetics. Like calculus and organic chemistry, genetics is an intrinsically interesting field that is easily spoiled by bad teaching.
The evidence so far suggests that SARS-CoV-2 does not mutate rapidly. That’s not why I will avoid infection. I don’t want to personally challenge my immune response because there is not enough known about this vaccine to be confident as to what level of protection it affords, particularly in the elderly (like me) or others with co-morbidities. We’ll know much more in the next 2-3 months, as the number of trial subjects who become naturally infected reaches statistical significance. I’m very patient.
Joel:
I would not challenge nature either. The fool in the White House suggests he is immune and others will follow his quackery. It is unfortunate he did not get sicker and stay sick for a longer time.
Back to school. I never realized how excellent my education was while attending an all boys high school. Three years of science, 4 years of math and English, etc. It was a magnet school at the time for boys replete with shops and architectural courses. More students graduated from there and achieved PhDs later (or so they advertise) than other schools. I was lazy and performed at an average level and rate.