Jon Yewdell writes:


Thought it would be useful to clarify some aspects of B and T cell immunogenicity, to extend your episode 634 discussion.

Protein based vaccines (purified spike, inactivated virions) will induce robust B cell and CD4 T cells responses, but zero to very weak CD8 T cell responses.  

Note that you can’t get a IgG or IgA immune response or B cell memory without CD4 T cell help.  Will only get a weak and transient IgM response.

Nucleic acid based vaccines (RNA, DNA, recombinant viruses) will induce B, CD4 and CD8 T cell responses.

Full-length spike-encoding vaccines will elicit Ab, CD4 T cell and critically,  CD8 T cell responses.  Indeed, the unusually large size of spike (1273 residues) means that it has a proportionally higher number of potential antigenic peptides.  Due to the major contribution of defective ribosomal products (DRiPs) to peptide generation, all viral proteins are sources of class I peptides.  For ER targeted proteins like spike, peptides can arise from translation products that fail to make it into the ER and from misfolded proteins exported from the ER back to the cytosol for proteasome degradation/antigen processing.  On top of this, there are probably peptides from low level translation of alternative reading frames.  I’ve attached a just published DRiP review and an old, but still relevant review on T cell immunodominance for some of the gory details.

Note that the Moderna RNA vaccine encodes full length spike while the Pfizer RNA vaccine link  encodes just the  receptor binding domain (RBD),  which ~6-fold smaller than full length spike,  encodes proportionally less CD4 and CD8 antigenic peptides. 

Another potential advantage of the Moderna vaccine is eliciting Abs to the non-RBD domains.  While these are likely to be inefficient or unable to mediate classic in vitro neutralization, they nonetheless may provide protection in vivo.  It is clear from flu studies in mice, guinea pigs, ferrets and monkeys,  that such non-neutralizing anti-HA Abs (including Abs specific for the stem) can protect against disease.  Many mechanisms potentially contribute to protection by these non-neutralizing Abs.  These include Fc based lysis of infected cells by NK cells and Fc based phagocytosis of virus. 

Your faithful listener,


Keith writes:

My daughter will be returning to Colby College in the fall and (see below) they will be testing everyone prior to arrival and then twice per week during the semester along with other measures. Looks like a very sensible plan. 

Why can’t others do this? 


Keith subsequently sent this tweet:

Alice Dreger (@AliceDreger)

7/7/20, 8:08 AM

1. Put all the undergrads in a closed arena together for 3 hours. 

2. Quarantine them with beer and condoms for 3 weeks. 

3. Carry out the bodies and send the rest back to class. 

This is why they won’t let me be a dean.

Alice Dreger

Author of Galileo’s Middle Finger

David writes:

Dear Vincent:

I love your show.  I’ve only been listening since this current pandemic started though.  It has been fascinating to learn about virology.  

I heard your frustration re University Administrators claiming they don’t have the ability to test their incoming students on one of the recent TWiVs.  Check this CDC guidance out – the Adminstrators you are frustrated with can now say the CDC advised them not to test.  And the reason the CDC states appears to be incredible:

“Testing of all students, faculty and staff for COVID-19 before allowing campus entry (entry testing) has not been systematically studied. It is unknown if entry testing in IHEs provides any additional reduction in person-to-person transmission of the virus beyond what would be expected with implementation of other infection preventive measures (e.g., social distancing, cloth face covering, hand washing, enhanced cleaning and disinfection). Therefore, CDC does not recommend entry testing of all returning students, faculty, and staff.” 

From CDC “Interim Considerations for Institutions of Higher Education Administrators for SARS-CoV-2 Testing


Rinat writes:

Hello  TWIVers ! 

I am a senior medical laboratory scientist from Israel. Here we are in the middle of the second wave – and unfortunately we’re not dealing with it so well, compared to the first wave. We are a little country, with  a high population density, and very intimate familial society habits, which means it is very not easy to keep on social distancing – physically and mentally.

I am an old fan of TWIV because virology has always been one of my favorite topics, both in university and in my professional career. 

A number of times on the show you were talking about the urgent need of ramping up the testings, and their key role in controlling the pandemic. But I don’t remember even one time that you mentioned the people beyond these testings: Medical laboratory technologists and scientists, which you can’t execute any lab test without them. Not every step can be done by robots and machines…

The medical laboratory profession is neglected for years by governments, globally, not only in Israel and in the US.  Medical laboratory professionals got used to being unknown, unheard and unseen beyond the curtain of samples. but now, as the demand for lab testing is growing, you must understand that the number of testing is not just a matter of money or available reagents. It is a matter of how many lab professionals out there to execute these tests. In addition, they have the best knowledge about sensitivity and specificity of the relevant tests. the decision makers should consult with them.

Attached hereto a letter from the American Society of Clinical Laboratory Science – ASCLS. As a person who is involved in the Israelian Society of Clinical Laboratory Science and as one who tracks similar societies in other countries and MLs facebook pages, I can assure you that the description in this latter is something in common to our profession globally.

If you are interested to hear more of the Medical lab point of view – I’ll be happy to be that voice. 

Keep doing what you are doing  😉


Letter from ASCLS

Erynn writes:

Hello Dr. Grumpy et al…,

I a man avid TWiV listener and while I, like many of the others, only heard about you when the pandemic started (well, it was an outbreak at that point), I thoroughly enjoy not only the coronavirus podcasts, but the non-coronavirus podcasts as well. I have gone back and listened to a number of them and have furthered my general virology knowledge. 

I am an educator at a local community college in Modesto, CA and like everyone else, we are discussing fall semester. Unlike many junior colleges, not only do we have general education science classes, we also have a great cadaver program which includes advanced dissection for students, a two year nursing program, and a 4 year baccalaureate respiratory care program. The students that make up our many science pathways include a fair number that already work in hospitals such as CNAs and scribes, or work in hospice care facilities. We also have a robust career and technical program and a lot of those students work in other high risk areas such as food processing centers (slaughterhouses and meat packing) and grocery stores. 

At the onset of this pandemic I was naive in thinking that we were going to get a conserved federal response and guidance. Well, here we are in July and those dreams have been dashed. We can no longer wait for a federal response as one will not be forthcoming (at least until Jan 2021). We must do this ourselves. I very much subscribe to the TeTrIs plan of testing, tracing, and isolating. The testing seems to be a problem though. Like many other places, we have some testing in the region, but not nearly enough. 

So, to the point of this email. I am proposing that our school do our own testing. We have PCR machines. We have an abundance of health science personnel. We have good lab capabilities. That said, our PCR machines are aging and through some round about funding sources, I want to get more machines. As scientists, do you have recommendations that you are willing to give out? Seems to me that any hope we have of being able to keep the majority of faculty (many of whom are in the at risk population), staff, and students safe we need to get this rolling as fast as possible. 

I love the podcasts. Especially the banter and occasionally submitted haikus. Stay pedantic, stay grumpy, stay safe. 

Erynn Lucas, PhD 
Modesto Junior College

Rona writes:

I am an eager listener of TWIV.

Can you comment on how you feel about the health aspects concerning the reopening of my son’s public high school on Long Island.  In bathrooms, using the air dryers? I suggested the school disable the dryers and provide paper towels. The Superintendent told me he just read a piece by WHO that says air dryers do not present a hazard since the hands should be washed and clean.  I said the issue is blowing the air around and the fecal droplets from the lidless toilets.  What can you tell me to convince him to disable the hand dryers?  Incidentally i asked if the bathrooms are vented and he said they are exhausted. To what rate, I dont know.

Also, would you comment on their plan to physically distance at 3 foot apart and have “mandatory” masks wearing? I am concerned about the portion who get exemptions from wearing.



James writes:

I love your podcast, and I am learning more from you folks than I would ever get from any other source.  But I wonder do you agree with me on testing.  I think the best way to fight this virus would be to test the asymptomatic population.  Even at the expense of testing those with symptoms.  I mean if you have symptoms you already know what you need to to do, which you probably should do anyway whether you have Corona or something else.  

I also wonder about two other issues.  I have heard you say there is no evidence of two strains of the virus, which I must set aside my feeling that the virus coming from Italy seemed to spread worse than that coming from China.  I have to agree a hunch is not science.  But I do want confirmation that allowing the disease to spread to get herd immunity is dangerous, because even if it doesn’t seem to mutate quickly, the more people with a virus the greater the chance that something such as a dangerous mutation will occur.  Is that good science.  It seems logical.   Also, is there any evidence of links between coronaviruses and long developing problems such as cancer.  I worry if people get this virus we don’t really know what damage its doing, and won’t for years to come.  Like we saw with the 911 first responders.

Thanks for your podcast.

Patrick writes:


I was wondering how difficult it is to engineer an attenuated virus, but with a much higher transmission potential.  Release of such a virus could confer population-wide immunity at lower cost than traditional vaccines.

It is easy to see how this could go very badly wrong and there are ethics problems.



Jonathan writes:


I am a new layman listener writing from southern Sweden where the temperature is 20C (68F), and it’s windy and rainy. I highly appreciate that the podcast presents research and informed discussion in a manner that appeals to professionals and non-professionals alike, even if I can’t follow everything you talk about. 

You have talked about the dangers of choir practice spreading covid-19, but only briefly mentioned playing of wind instruments on TWiV 611 while discussing a Guardian article ( I am a member of a brass band that cancelled all practice and performance during the spring, and I wonder what we will do in the fall. Like with singing we push air out of our lungs with force, but the air goes through the instruments. Moisture from our breath condenses in the instruments which we regularly release through valves. I suspect most of the droplets and aerosols would also get caught. The Guardian article mentioned that risk of spread varied with the size of the instrument, which makes sense since the longer distance for the air should mean more filtering. I am worried  that some smaller instruments like trumpets might spread the virus. I wonder what you think.

Keep up the good work


David writes:

Great programme, people!

Follow-on from the question about thalassemia. Both thalassemia and sickle cell disease patients  will potentially have a sickle crisis when very ill, adding to the coagulopathy with COVID19. 

Possibly something that will be investigated retrospectively.



Ed writes:

Greeting From the Peoples Dictatorship of San Francisco, Where it is about 509 degrees Rankin. 

From my understanding,  the Fahrenheit scale is better for weather and normal usebecause the range is more expanded, not so compacted like the Celsius scale.

Also, under normal conditions, when you use the Fahrenheit scale you do not deal with a negative temperature like the Celsius scale. Both the Rankine and Kelvin systems do not use negative degrees, because the concept is not thermodynamically or scientifically correct. 

One of my favorite quotes is from Goethe “To know is to measure” and the other is mine “Mathematics gives discipline to Science”

Now to questions, I have never taken a class in Biology, but love your podcasts. Also, I get lost by the terminology, but try to get the concepts. 

For example, you say viruses are not alive, but you also say you kill viruses. ( I will not say who on your podcast has said that, to protect the guilty) Should it not be that viruses are denatured?  How can you kill something that is not alive? 

Another example, I first heard about sterilizing antibodies, next it was neutralizing antibodies, and now hear you guys say protective antibodies.  And sometimes I hear used the term “antigens,” and then I hear used “pathogens.” What is difference? Do I need a Venn diagram to understand?    

Another question, when there is a COVID-19 outbreak at a food processing plant, can the virus be transmitted by the frozen food? China thinks so! Would not when the temperature goes to freezing, ice crystals would form and destroy the virus? Or does the virus crystallize? 

In Science words should have an exact meaning. I think Vincent knows that, because he asks about the difference between data and datum. But who takes high school Latin anymore? And they are not  teaching my grandkids cursive handwriting in school. We do not have standards anymore, and this country needs to switch over to the Metric system, so science will come more natural to the kids.