Andrew Macadam writes:
What a nice surprise to hear you all talking about nOPV2 on TWiV! Wonderful discussion, thanks for your kind remarks about our paper, and for your supportive review (the paper eventually came out in May 2020). As you rightly say the concepts behind the vaccine design came out of basic scientific research in many labs, arguably starting with infectious cDNA and the analysis of David Minor’s nappies. If things go well this could be a great example to use in future grant proposals (“bench to bedside”).
To update you with what’s going on in case you are interested, results of the Phase 2 trial and a second Phase 1 are now published in Lancet (De Coster et al 2020 and Saez-Llorens et al 2020) showing very similar findings to the first Phase 1 but in more, and younger, people. We all know polio can usually find a way to revert given enough opportunity but the hope is that the frequency of this will be reduced sufficiently to prevent new cVDPVs. Remember that mOPV2 itself gives rise to cVDPV transmission relatively rarely and even a 10-fold reduction in this would have a big impact (of course we anticipate even bigger reductions!).
Other clinical trials are in progress or are planned including a Phase 3, required for full licensure, a trial in naive infants and Phase 1 studies of nOPV1 and nOPV3.
If I was to be pedantic I would pick you up on a couple of things. Regarding recombination, I think you misremembered the observations in tOPV recipients where intertypic polio-polio recombinants are common – recombination with other species C enteroviruses has only been found in cVDPV isolates to my knowledge. And for domain V, attenuation correlates with thermodynamic instability rather than the other way as you said. It is hard for S15 domain V to regain stability and hence revert because that would require more than one double-mutation converting a U-A into a C-G base-pair. Destabilising would be easy. Also, on behalf of our CDC colleagues, the codon deoptimization in candidate 2 came from work in Cara Burns and Olen Kew’s lab, not Eckard’s. This candidate was found to be marginally less immunogenic than candidate 1 in the Phase 2 trial, hence the decision to proceed with candidate 1. The lower/shorter excretion that you commented on could of course be advantageous with respect to onward transmission (but less so with respect to herd immunity a la Albert Sabin).
Happy to fill you in further if you have any questions.
Division of Virology
I’m the Chief Operating Officer of a big European direct to consumer media and communications company. I lead our work to keep our staff and customers safe through Covid. TWIV has been brilliant at giving me better context to make risk decisions for our day to day operations, including our approach to working in customer homes and workplace testing. If you’d told me 12 months ago that I’d be listening to a Podcast on viruses, I’d never have believed you.
But that’s not what I’m emailing about. In episode 747 you mentioned the $25 Antigen test now available at pharmacies in the US. I thought you might be interested to know that the National Health Service here in the UK has from March offered self-swab antigen tests for free to anyone who wants them. They’re distributed through workplaces, pharmacies, online, and also through schools where a twice-weekly test is mandatory for everyone over 12. The tests used are produced by Innova and Surescreen. The NHS recommends that everyone tests themselves twice per week. Results should be reported through the NHS Covid-19 App, and positive results are followed up by a (free) PCR test which determines whether continued quarantine is necessary.
I just had to pause TWiV 754 after hearing your listener’s email about a weeks long migraine following vaccination. These symptoms are consistent with the rare clotting reported in females after being given other vaccines. Clots blocking the sinuses cause pressure build up in the blood supply that drains into the blocked sinus.
Maybe the prefusion stabilised spike protein in the vaccine she had reduces the chance that this can happen, so we haven’t seen deaths following the mRNA vaccines, but you just read a paper about the effects of the E protein in a related mouse virus, one could easily imagine a possibility that the spike in humans could have some other effect, even if rare.
Unless somebody who knows something can explain that I am wrong (very possible, I have no experience in the field) please advise listeners to take post-vaccine migraines more seriously, esp in the high risk group, females 18-49. Ibuprofen is probably a good call to reduce inflammation. Also, remind them to use the vaccine adverse effects reporting system, so the right people can pick up if there is any signal. Facebook groups are not a substitute.
Now back to the video 🙂
Drs TWiV, esp Vincent:
Not sure if I sent you this one before, but it would’ve been a great addendum to the paper discussed in #753 re. vaccine-related polio outbreaks. This is a short reminiscence from the son of the head of a prominent Pittsburgh nursery/landscaping business (still going strong!). Jonas Salk was one of their clients, and they had the bad luck to be working next door on the day he proved that his vaccine worked. Esp everyone in polio research should know this story.
(“Bullet-nosed” Studebakers were the ’50 & ’51 models)
in Greater Braddock, where it’s sunny and warming @ 54F/12C
Hello Vincent, Dickson, Kathy, Rich, Brianne, Alan, Amy and Daniel
First of all thanks to all of you again for all that you do and have done throughout this pandemic. I think I may have mentioned this before that I actually started listening to TWIV while I worked in the Middle East during MERS and then, like now, your podcast has been an island of objectivity and common sense in a sea of disinformation. I pray and hope every day that more people will listen to you instead of the mass and social media : ).
I am writing to ask for your thoughts on the following:
-I took the Astra Zeneca vaccine here in Canada last month as it was the first one available and I am considered an essential worker. To borrow Daniel’s phrase; I took that opportunity to vaccinate. Needless to say I’m still alive, and apart from a sore arm for about 24 hours had no side effects. Unfortunately as you may be aware the AZ vaccine has had some bad publicity (bordering on hysteria in my opinion) about blood clots post vaccination.
-The Provincial government here in Ontario Canada, has decided to stop giving it as a first shot and has announced that those of us who had it as a first shot now have the option of taking it as a second shot or getting one of the other vaccines which would be Pfizer or Moderna.
-The study cited for doing this (apparently unpublished) stated that there is the possibility of 0.9 people out of 100,000 people getting a blood clot which the mass media then decided to round up to 1 person in 55,000 (Interestingly a study in the UK, one of the largest users of the vaccine, found that it was less than half this number from a much larger population sample https://www.bmj.com/content/373/bmj.n931).
-Considering that 5.4 people out of 100,000 in this province run the risk of getting into a fatal motor vehicle accident, I’d say that AZ is still safer, but hey, that’s only me and it pretty much sums up that saying “there are lies, damned lies and statistics”.
My questions are:
-Could there be any adverse side effects from switching to one of the other vaccines for the second dose?
-Would there be any risk of reduced immunity against SARS Cov 2 resulting from using one of the other vaccines as a second dose?
-Would the J&J vaccine be an option as a second dose? It is apparently available but I am not sure on how it is being rolled out here.
To be honest, I will take AZ as a second dose if offered (given that I am pretty sure that I am not in that 0.9 out of the 100,000 cited) but I do know people who would prefer to switch given all the publicity around it.
Finally, I was sad to hear about the passing of Thomas Brock, although I never pursued a career in it, my undergrad degree was in Microbiology and I, like pretty much everyone who went down that road, started with his “Biology of Microorganisms” and had to lug that book around campus!
Thanks again for all you do and all the best to all of you.
Hello amazing TWiV team!
This is Alli from Virginia Beach again, the hockey mom and volunteer epidemiologist. This is my follow-up report: baseline plus post-dose 1 spike IgG report.
Two months ago I wrote to you about my post-covid antibodies. Well, I couldn’t resist chasing this down further. I ordered (via the Internet) a second antibody test from Quest Diagnostics a semi-quant IgG test (code 34499).* Both results are attached.
My first result 4.5 MONTHS AFTER NATURAL DISEASE was 11.21 on an index that was very vague: >1 is considered positive, but I was not at all sure what 11.21 meant. I thought it was at least good, I did some digging, which I shared with you in my last email.
Now I have results back ON DAY 21 PFIZER POST-DOSE 1! My result was >20. I was annoyed again, because not only was this vague, there is no reference range.
My conclusion? People with natural disease (PCR or antigen positive) probably don’t need two shots. The body “saw” all 25 proteins of SARS-CoV-2 in the first battle against the virus. The vaccine shows 1 protein (spike) and boosts immunity quite well to the immunodominant antigen.
On the day I got dose 1, I ordered my TWiV sweatshirt so that it would arrive as a reward for going through with two doses as recommended. I proudly wear it to the hockey rink now. When I see new faces above the mask, I thank them for being gracious with protocols and introduce myself in case they have grievances or feedback. I figure it is best to keep a wide open door to conversation about all of this as we move through pandemic to endemic SARS-CoV-2. Precautions will modify as we learn more. Last night a man replied to this introduction by asking: “Oh, are you a PhD or MD?” I paused and replied “neither!” with a bit of a chuckle. “I’m just a boots-on-the-ground epi.”
I keep trying to learn everything possible through incredible teachers like all of you. I am so profoundly grateful. It’s a real joy when I anticipate a question one of you raises!! I literally talk to myself while running and pump my fist in the air when I nail a question with a remotely similar response. It’s like taking the APs again 😉
Thanks a million!
Alli in Virginia Beach
*Nitty gritty details: This is the test an individual can order and pay for directly from the Quest website. It was $119 when it first came out in March, now it is $78. If you order the antibody test, this is the one that pops in your cart. You have to pay for it, then schedule the appointment.
~ I’m not lost if I know where I am.
~ “He went to the cities, I went to the forests.” (Chateaubriand of de Tocqueville)
Dear TWiV Team,
It’s been a long time since I have written; still enjoying your scientific chats.
I’m on an NIH mailing list that recently shared a summary of two studies of COVID-19 deaths with potentially fruitful results. It is at
I am only an accountant, but I do tend to notice numbers and expect them to make sense. My take from the article is that the studies used samples from at most 30 victims of the disease: Izar’s (Columbia) 19 men and women and Regev’s (MIT) 420 samples from 11 organ systems (possibly two or more organs from the same individual, so less than 11 individuals?).
Yet in the concluding remarks the article goes “The hope is that these vast data sets (emphasis mine) together with future analyses and studies…will improve our understanding of long-term complications in patients who’ve survived.”
Wait a minute – vast? How did we get from so few victims to vastness? The fact that the study data will be made available to researchers world-wide and the potential for more advances in dealing with this disease are both good news. I hope it is not being exaggerated, and it is just my failure to understand.
Whidbey Island, WA
Dear TWIV Team,
It’s the same temperature in Bangkok as the last time I wrote 🙂
You probably have seen this already but just in case:
I have a question for Brianne: Why do immunologists seem to prefer reporting antibody concentration levels in AU/ml rather than ug/ml? Perhaps I am old-fashioned (or just old), but I was taught that proteins actually have mass. My main concern is not really the use of AU/ml but that many papers don’t link these to ug/ml units. Please explain if you have a chance. From my readings it seems that post-Covid IgG serum concentration levels range from about 1-50 ug/ml after 2 weeks. Is this correct based on what you know?
Thanks for your continuing work.
All the best
Re: Amy’s comment on Twiv 756:
Canada’s vaccine plant history is basically: we had two major plants (see e.g. history on Connaught Labs). Connaught was nationalized, then privatized, and ultimately sold to foreign ownership. Both owners (GlaxoSmithKline and Sanofi) downsized the Canadian facilities during corporate takeover. Canada was ultimately left without vaccine manufacturing capacity because concentrating manufacturing at overseas plants was deemed more streamlined.
Canada has now announced millions to build a new plant. All this is detailed in the article below.
Vincent, you’re right to be upset with the idea that Canada wouldn’t be investing in vaccine manufacturing after all this! Good thing it’s not true. Hope this good news makes you less grumpy 🙂 (you haven’t been so grumpy lately, just a joke).
Cheers, keep up the great work. Loved hearing about TLR2 since I work on NF-kB signalling. Fascinating stuff!
Periodically someone mentions “put in Show Notes,” which sound very interesting but I cannot find them.
Are Show Notes private to the speakers or available to all?
Dave MacQuarrie MD PhD
At least, with COVID, some people seem to recover completely. In contrast, if you’re a cicada, and with Massospora:
Hi TWiV team
I’m a listener from Dublin, Ireland. My own background is in computer network engineering, but I’m basically a nerd of a different colour. A little over a year ago, I realised I didn’t know what mRNA is, and so spent this past year delving deeply into molecular biology and virology. To say that it has blown my tiny mind is an understatement. As part of my nerding on these topics, I came across your podcast and have been hooked ever since. While the discussions often go over my head, they serve as pointers to topics to subsequently explore more deeply. It’s been a trip!
Anyway, among my other interests that overlap with frequent picks of the week are all things space related. Recently you have marvelled over various SpaceX feats and so I thought I’d draw your attention to this book:
“Liftoff: Elon Musk and the Desperate Early Days That Launched SpaceX” https://www.goodreads.com/en/book/show/53402132-liftoff
The book covers the early years of SpaceX, from founding through to their first successful orbital flight. It is a heck of a story and a great read. I’m certain you will enjoy.
Thank you for all that you have done over all these years, but especially in this past year in sharing your knowledge and experience with the rest of us. You have done a great service.