Tim writes:

Hi TWiV team!

Listening to episode 890’s discussion on infection interval affecting the immune response, I was reminded of Daniel Griffin’s comments on one of the differences between vaccination and infection-based immunity. His take is that when you get infected, you don’t really know what the infectious dose was, or the viral titers during infection, so you don’t really know what your immune system was exposed to. This variable of differing “doses” could have an effect on the quality of the immune response. After all, we wouldn’t tolerate our doctors administering a random amount of vaccine – we would want a controlled dose with predictable response.

I’m wondering if this could be a contributing factor to the infection interval study that might not be applicable to vaccine schedules. My guess would be that the closer an infection was to the most recent vaccine, the virus would be cleared faster and would not reach as high of a peak burden due to residual circulating antibodies etc. By the time somebody reaches six months post-vaccination, circulating antibodies would be mostly gone and the virus would be able to have a more productive infection (at least initially). So, in addition to the time interval between vaccination and infection, a confounding variable might just be differences in the amount of viral antigen the immune system is exposed to – with longer intervals leading to higher viral loads leading to a more robust immune response.

All this is not to say that the interval doesn’t matter from the perspective of maturation of the immune response, as other papers you have covered using vaccine schedules clearly show a role. Thoughts?

Love the show. Thanks for all you do!

Tim

Dave writes:

Hi TWiVers:

Pre-covid listener!  I was under the impression that China’s Sinovac vaccine was terrible compared to the current crop of mRNA vaccines, due to early clinical trial results, and my assumption that a killed vaccine would not induce decent T-cell immunity.  I did not expect Sinovac to confer durable protection against variants since I assumed it would induce a primarily humoral response.  However, this preprint from HKU (https://www.medrxiv.org/content/10.1101/2022.03.22.22272769v2.full) claims that three shots of Sinovac is very effective against severe disease, even in omicron:

“We estimated three doses of both vaccines offered very high protection against severe disease (98.1%, 95% CI: 97.1%, 98.8%) and mortality (98.6%, 95% CI: 97.7%, 99.2%) which was sustained within all age groups (Table 2). Vaccine estimates were very similar for both vaccines against severe and fatal outcomes. Three doses of BNT162b2 was estimated to have a VE of 71.5% (95% CI: 54.5%, 82.1%) against mild/moderate disease in younger adults while for three doses of CoronaVac the VE was estimated as 42.3% (95% CI: 11.4%, 62.4%) against the same outcome.”

How does this work?  I assume Sinovac has not been updated to an omicron strain formulation and is still using parental Wuhan strain, but have no data.  Do coronavirus virus particles that have been killed with β-propionolactone still transduce cells and present antigens like an mRNA vaccine?  

Thanks for any discussion and correction of my mistaken assumptions.

Dave in Oakland

Wendy writes:

Dear Vincent and TWiV crew,

This is Wendy Xu, a recently defended Ph.D. student from UT Austin. While other people are writing to thank you for providing objective scientific information to the public about SARS-CoV-2 and COVID, I am writing to thank you all for your long-term education efforts for the public. And it is really due to Vincent and TWiV’s education effort that I decided to start on a virology research training path, and now a Ph.D. with a dissertation focusing on retrovirus!!! 

In episode 884, when Vincent was complaining to Amy that Columbia did not have virology lectures in the basic “Frontier in Science” class which is required for every student, I was literally shouting saying yeah that was exactly what happened in my undergraduate training! Even as an undergrad biochemistry major, we did not have a virology class! And that was the time (~2013) I looked for an online virology class and found Vincent’s virology on Coursera. I was so fascinated by viruses from your course and from TWiV at that time, so I made up my mind to do virology research, although my undergrad institute did not have a single virus research lab. Eventually, I got admitted to the Ph.D. program at UT Austin and started working on viruses! When I just joined UT, you held the No.500 “epitope” on our campus, my labmate got a TWiV T-shirt and I was so jealous!!! But it was so nice and enjoyable to see you live at that time! And I was even more excited and very honored when I found out one of my co-authored papers published on mBio earlier this year (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725593/ ) was actually edited by Vincent. You know what, when we realized this, we did multiple passes of proofreading before we returned it to you. 

I will attend the Cold Spring Harbor 50 years of Reverse Transcriptase Meeting in late April, and I notice from the program book that you are holding a TWiV there!!! I am not sure who else will be there but I believe at least Vincent will be there? I am presenting a poster at the meeting. So if you have time, come and check out my poster in the poster session right after your TWiV session! It is a different story than the mBio paper you edited.

Thank you again for your long-term education on viruses and science for the whole public. I am sure there are many other trainees out there inspired by Vincent and the TWiV team, and starting their virology research journey. I am very grateful for all you have been doing. Thanks for reading this long letter!

PS: my weather in Austin should be the same as what Rich is experiencing, very sunny, 62 to 89F and bluebonnets are blooming everywhere in Austin!

Sincerely,

Wendy

— 

Wendy Kaichun Xu (Ph.D.)

Department of Molecular Biosciences

The University of Texas at Austin

Austin, TX

Ginny writes:

I’m afraid I’m about a week behind, so someone else may have already told you this.

On the April 1 show, you mentioned that the bagel joint has a picture on the wall of a bagel with lox with the caption, “This is not a bagel.” This is a joking reference to the painting “The Treachery of Images” by Rene Magritte, which shows a pipe with the words “Ceci n’est pas une pipe.” (Which translates to “This is not a pipe.”) Magritte meant that it was the representation of a pipe, not an actual pipe. Take-offs on this, like the one in the bagel store, are an in-joke, since only people familiar with the painting get the joke. The bagel joint wasn’t saying that a bagel with lox and cream cheese wasn’t a proper bagel, it was making a joking allusion to art history.

https://en.wikipedia.org/wiki/The_Treachery_of_Images

In case you’re ever up here and crave a New York-style bagel, the best bagels in greater Rochester, NY, are made by Bagel Land. They do offer maple bacon cream cheese, which is delicious! They also sell “bagel dogs,” which is where they wrap a Rochester-made Zweigle’s hot dog – which has pork – in bagel dough before cooking it. They are delicious, and absolutely tref. You can also get a pizza bagel with pepperoni and cheese. Also tref. The store isn’t kosher, but their water bagels are the real thing.

Best to you all,

Ginny

Patrick writes:

Dear TWiV,

I’m listening to your episode on yellow fever vaccines, and it seems that you are unaware that Sanofi is currently in a phase 2 trial of a new yellow fever vaccine. I am in the trial here in Boston, having been jabbed with either the existing vaccine or the experimental one back in January.

https://clinicaltrials.gov/ct2/show/NCT04942210

Keep up the good work.

Patrick

Chris writes:

Hello TWIVvers,

Why is it that each new strain of SARS-CoV-2 completely eclipses the previous one? 

One can see how one strain might have higher infectivity and a greater number of cases over time, but why do the less infective strains go away entirely instead of just continuing to spread at a low level?

You can’t find Delta now, but it did fine before Omicron came about. Why did it go away?

Thank you for the great podcast!

Chris in Seattle

Steve writes:

Hi Vincent et al,

I’m sure that TWiVsters everywhere will find Michael Lewis and Al Franken give a good account of some of the fundamental shortcomings in US epidemic preparedness, in their discussion of Lewis’ new book: ‘The Premonition: A Pandemic Story’. (My only quibble would be that they don’t dig deeper into the root cause, which lies in the human nature of tribalism that George Washington warned, in his Farewell Address, would leave governments unable to act when the people

most needed them, if political parties were allowed to take control. We are living the future he predicted, right now.)

Best wishes,

Steve in Luton, England.

(Where our three party system makes change, if anything, even less possible than in the USA.)

Kent writes:

Hi Dr. Racaniello and the rest of the TWIV gang.  Thank you for what you do.  Extremely helpful – including in this time of continuing pandemic.  I have been a regular listener since the beginning of the SARS-CoV2 outbreak.  A question came to my mind as I took my usual walk this morning in a beautiful 61 degree F cloudless sky in Charlotte, North Carolina.

Has anyone studied viruses that have adapted to life in the canopy of trees?  One of the continuing themes from the last 6 months of TWIV has been that we don’t do enough field work.  I can easily see that increased field work could be one of our most powerful ways to prepare for the next pandemic.  I teach my students the “drunk under the lamppost” story, so as I walked this morning looking at the fully bloomed green leaf canopy, I was reminded that the canopy is not a well-studied bioenvironment – possibly because it is onerous to set up observations/experiments high in the trees.  When I think about canopy, I think of the Amazon jungle, but the question could equally apply to North American forest.  I fully appreciate that virology in the canopy also means study of other lifeforms in the canopy.  In the several hundred episodes (or dare I say “epitopes”) to which I have listened, I have never heard anyone mention canopy.  I realize that this question from a non-biologist might sound silly, but I feel that I have to at least ask. 

Kent

Kent D. Stewart, Ph.D.

Associate Professor of Pharmaceutical Sciences

High Point University

High Point, North Carolina