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Sunday, 24 December 2017 16:27

TWiV 473 Letters

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Published in Letters

Joseph writes:

Greetings again TWIV docs,

As someone who worked on identifying physiologically relevant CD8+ T cell epitopes for potential dengue vaccines, thanks for covering the latest on Dengvaxia. The background scuttlebutt in our biotech circles probably led to skepticism  about this vaccine but now the data is emerging. It’s a bummer, because an effective Dengue virus vaccine for all individuals is very much needed.

Following up on Scott Halstead’s CD8 T cell recommendation, we’ve hit that pretty hard over the past few years. I’ve included some links to publications from my former lab at Immunotope, Inc. on these topics. The super quick summary is that we used immunoproteomic approaches to identify HLA-A2 and HLA-A24 restricted CD8 T cell epitopes derived from dengue virus proteins. We’ve demonstrated that a number of these epitopes are conserved between the four strains and can induce cross-reactive CD8 T cells responses (at least in humanized mouse models). But because mice lie, we did find CD8+ T cells that recognize these epitopes in DV seropositive patients.

    I think the antibody vs. T cell argument will forever be a part of vaccine circles. But I agree with Rich – both arms of the immune response are probably necessary for full protection and vaccines that can induce protective antibody and CD8 T cell responses will be ideal.

Links:

  1.      Conserved MHC class I-presented dengue virus epitopes identified by immunoproteomics analysis are targets for cross-serotype reactive T-cell response.
  2.     Dengue virus specific dual HLA binding T cell epitopes induce CD8+ T cell responses in seropositive individuals.
  3.     A novel immunization approach for dengue infection based on conserved T cell epitopes formulated in calcium phosphate nanoparticles.

  And I just became a Patreon supporter! Thanks for all you do for promoting virology (and almost every other –ology) and science communication!

– Joe

Joseph Comber Ph.D.

Instructor, Biology/Human Anatomy and Physiology

Villanova University

Anthony writes:

In TWiV 471, there was mention that in some cases the first infection with Dengue is severe.  Is it known for certain that these really are first infections?  Might it be that there was a prior infection so mild that those people did not even realize that they were sick?

FWIW

Martin writes:

Be sure to thank the Donald for this

‘Nature is a terrorist and we have to stay ahead’: US lifts ban on pandemic pathogen tweaks

https://www.rt.com/usa/413692-pandemic-pathogen-research-moratorium/

Martin K. Barnes

Mark writes:

Dear Vincent and supporting TWiVers,

I’ve written for TWiV the below poem inspired by the classic “The Night Before Christmas.”

Happy Holidays.

Mark

——————————————————————————-

‘Twas the night before tenure review, and all thro’ the city

Not a creature was stirring, not even Vinny

New papers were hung by the chimney with care

In hopes Science, Cell, or Nature would soon pick theirs

The postdocs were nestled, all snug in their beds

While visions of funding danc’d in their heads

Ma in her ‘kerchief, and I in my cap

Had settled our brains for a long winter’s nap

When out in the lab there arose such a clatter

I sprang from my bed to see what was th’ matter

Away to the NEIDL, I flew like a flash

Tore open vacuum locks, and threw on my mask

The moon on the breast of the new fallen snow

Gave a plaque assay’s lustre to objects below

When what to my wondering eyes should appear

But a miniature sleigh, pulled by eight viridae

With an old driver, so lively and quick

I knew in a moment, that it must be St. Dick

More rapid than a trout jumps, his followers they came

And he whistled and shouted, and call’d all by name

“Now! Picorna, now! Toga, now! Arena, and Flavi

“On! Bunya, on! Corona, on! Astro and Reo

“To the top of the sequencer, and the Great Polio Wall!

“Mutate! Mutate!, Mutate away all!”

As lab techs and postdocs, before tenured faculty fly

If they meet with an obstacle, they just want to cry

So to the bench-top, the coursers, together they flew

With the sleigh full of phages – and St. Dickson too

And then in a twinkling, I heard on the roof

The prancing and pawing, of each little hoof

As I drew in my head, and was turning around

Down the chimney, St. Dick — he came with a bound

He was dress’d all in fur, from his head to his foot

And his clothes were all tarnish’d with dye stains and soot

A bundle of Dick’s books, was strung on his back

And he look’d like a peddler, opening his pack

His eyes – how they twinkled! his dimples how merry

His cheeks were like roses, his nose like a cherry

His droll little mouth, was drawn up like a bow

And the beard of his chin, was as white as the snow

The stump of a pipette, he held tight in his teeth

And mist encircled his head like a viral capsid wreath

He had a broad face, and a little round belly

That shook when he laugh’d, like a bowl full of jelly

He was chubby and plump, a right jolly old elf

And I laugh’d when I saw him, in spite of myself

A wink of his eye, and a twist of his head

Soon gave me to know, I had nothing to dread

He spoke not a word, but went straight to his work

And fill’d the stockings with his sixth edition book

And laying his finger aside of his nose

And giving a nod, up the chimney he rose

He sprung to his sleigh, to his team gave a whistle

And away they all flew, like the down of a thistle

But I heard him exclaim, ere he drove out of sight

Happy Christmas to all, and to all a good night

Sean writes:

Good morning from sunny Southern California twivsters!

I’d like to offer some perspective as a newly minted PhD and postdoc to the discussion in your “Just a passing phage” podcast about work life balance in the sciences. To the listener(s) afraid of pursuing grad school because of the long hours, I want you all to know that it is possible to strike a healthy balance between work and your personal life as a grad student. In fact, it’s paramount for survival.

I certainly spent more than 60 hours a week working when it came to bench work, presenting data at lab meetings, teaching reproductive health classes for LGBTQ students in the dorms, and my TA-ships (even more hours while grading). Grad school certainly isn’t for wimps.

However, I did have plenty of time for extracurricular activities such as line dancing, getting involved with the public health student association, and attending my fraternity’s events on campus (special shout out to Delta Lambda Phi). To manage my time, I used Google Calendar to its limits as well as other smartphone apps (e.g., Asana) to maintain my schedule and project deadlines with my advisor. Here’s a link that might help: https://asana.com/ Time management is one of many skills I had to learn in order to maintain a healthy balance and stay sane.

To summarize, it’s possible to be a social butterfly and a scientist as long as you’re organized and love what you’re studying. Public Health Microbiology is certainly a lifelong love affair for me.

Currently it’s 62 degrees Fahrenheit and sunny in Los Angeles with 12% humidity and 1mph winds. The leaves are finally turning color and it feels like fall after what was a seemingly endless summer.

Keep up the good work and wonderful podcasts,

Sean

P.S. I am unsure if the book contest is still ongoing, but if it is I’d love to throw my hat in the ring.

Teo writes: 
Dear TWiV Team,

 I am writing you today to thank you for all that you do for myself and others. I am currently a Senior at California Polytechnic State University where I am a double major in Microbiology and Cell and Molecular Biology. I am headed into my last quarter and I am currently applying for various graduate programs. I wanted to thank you for giving me so much to think about as I navigate the application processes and consider my options in industry. I am not a traditional student and only began attending college at the age of 25. You all have helped to expose me to possibilities that I may not have otherwise heard about, such as clinical microbiology technician. Your frank discussions on the current academic atmosphere of graduate school has allowed me to put my options into a more realistic light. And most importantly you have helped to keep me engaged and excited about the pursuit of discovery through experimentation.

 I have become more and more interested in Virology and Immunology as my educational career has advanced. I added Microbiology as a second major for the pure fact that I wanted to be able to take Virology, Immunology, Medical Microbiology, and others. Currently I work as a lab assistant in a local biotechnology company where we use corn as an expression system for producing conjugate protein vaccines. I cannot tell you how lucky I feel to be studying and working on things that I know are making a positive impact on the people in the world around me. More than just a few years ago I had no prospects past working in restaurants my whole life. Although I enjoy food and cooking I wanted to be able to make a larger impact on people’s lives. I want to encourage anyone else who took time off after high school to pursue what they are passionate for and to never tell yourself that it is too late or you are too old. If you can make memories you can learn. Although I am writing in in hopes of winning the book it was way past time for a thank you from me to you. Thanks again for your immense contribution to society and science.

Teo as in Mateo

Bill writes:

Germane to the grad debacle looming: https://www.scottaaronson.com/blog/?p=3542

Samer writes:

Hello again,

Although I risk developing a reputation as an animal trivia fact checker, I’d like to touch on 3 points for listeners that might not be familiar with animal research.

First, there is a back-and-forth about rats being “bigger mice” in this episode. This is simply not true. The rat and mouse lineages diverged 12-24 million years ago, about the same time the common ancestor of all apes diverged from the rest of the Old World Monkeys (https://academic.oup.com/mbe/article/20/3/424/1035768). And that is at the short end of the range. Physiological differences between mice and rats may make one or the other better models of human infectious, metabolic, traumatic, or other types disease. These are things to keep in mind when developing any animal model. Kudos to Amy for considering the Zika studies in the 40s and 50s that didn’t reveal virus in any wild rats when designing her experiments.

Second, a small correction on rodent comparative anatomy. Amy incorrectly states that rats do have gallbladders and mice do not, but it is the reverse. Mice have gallbladders and rats do not.

Third, a comment on laboratory rodent pricing. Amy is not kidding when she means that laboratory-bred rats and mice are expensive! In an effort to standardize animal models and limit variability between animals used in experiments (at least from a single vendor), much effort and many resources have been put into keep laboratory rodents free from specific pathogens, genetically standardized, provided complete and standard nutrition, all while in a narrow range of ambient environmental conditions. All of these things combined increase the price of animals above what you would see for “fancy mice” at pet stores. Although it is true that when comparing a standard outbred stock of mouse and a standard outbred stock of rat, the rat is more expensive (they take more resources because they are ~10x bigger), very specialized genetically modified, hard to breed mice may far exceed the cost of some rats. Some large rodent vendors even put their pricing on their websites and listeners can see for themselves.

Best,

Samer

(/səˌmēr/, rhymes with “come here”, more commonly spelled Samir or Sameer)

Samer Jaber, DVM

Peter writes:

Greetings TWiV team.

Currently on the Mediterranean coast of Turkey where halfway through September it is still hot and dry: 33°C and 54% humidity.

With the flu season approaching I was wondering about how the new batches of seasonal flu vaccine are tested. Obviously lengthy approval trials would not be a viable option for the annual seasonal influenza vaccines. I presume that the new batch is treated as an update of existing influenza vaccines made using established manufacturing protocol. Are any new clinical trials required or are the new seasonal vaccines on the manufacturer’s existing license.

Regards Peter

Stacey Schultz-Cherry replies:

Great question with a complicated answer. Every new lot of influenza vaccine must be tested for potency and safety, even if the viral strain components haven’t changed. This is typically performed by the government regulatory agencies. In the US that would be the FDA. If there has been a change in the viral strain, the regulatory agencies or even the vaccine manufacturers could request a small endpoint study to show efficacy. Obviously, clinical data would be needed if a group is applying for licensure of a new seasonal inactivated influenza vaccine. A few good references include:

https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm074794.htm

http://www.who.int/biologicals/publications/trs/areas/vaccines/influenza/Human_pandemic_Influenza_Vaccines_BS2074_01Feb08.pdf

This is a great overview of the strain selection process, vaccine production and regulatory approval timeline

https://www.tga.gov.au/community-qa/influenza-vaccine-annual-southern-hemisphere-influenza-vaccine-production-and-regulatory-approval-timeline

The timeline is for the Southern Hemisphere, so for the Northern Hemisphere, just add 6 months to any month in the timeline.

https://www.cdc.gov/flu/protect/vaccine/how-fluvaccine-made.htm

John writes:

Hi,

My name is John and I am a 3rd year Microbiology student at the University of Glasgow. Just want to say that your podcasts make my everyday more interesting. The first episode I listened to on TWiV had a former student from University of Glasgow which caught my attention, and now I am hooked!

Keep up the good work,

Cheers!

Anthony writes:

GGO in Dutch = GMO in English

Dr. Condit is correct.

http://www.ggo-vergunningverlening.nl/Algemeen/Wat_is_een_ggo

Now back to the regularly scheduled dish washing.

Thank you.

Welkin writes:

Hi Vincent et al!

I’m dragging behind in my TWIV listening, but after Vincent’s visit to Boston in August I skipped ahead to TWiV#455 (Pigs and Genes). The paper is indeed a marvel, with the simultaneous knock out of a couple of dozen functional ERVs in single nuclei, and production of PERV-free pigs. Since it wasn’t discussed on the show, I wanted to point out that the PERV loci are still transcriptionally active; the PERV are only rendered nonfunctional with respect to production of infectious virus (due to mutations in the viral pol gene). This has implications for recombination!

You don’t have to go any further than the archives of the Goff lab to find an example of a pol-defective retrovirus being rescued by viral recombination – most likely by co-packaging of RNA genomes and recombination during reverse-transcription. This happens because retroviruses package two copies of the viral RNA in one virion, and because RT can jump back and forth between the two RNAs to produce a recombinant provirus. Retroviruses are also known to package heterologous RNAs, which is likely how they acquire new genes (e.g., oncogenes).

From my understanding of the PERV paper, because these loci can still be transcriptionally active, this form of recombination remains a distinct possibility – i.e., recombination with another replicating retrovirus (whether it is expressed by an ERV or an exogenous infection) could still occur, resulting in repair of the pol defect and production of a replication-competent virus. For that matter, if the mutations in the PERVs themselves are not identical, it is also formally possible that two or more PERV loci could work in trans to generate virions with co-packaged RNAs that produce RT-mediated recombinants.

The paper from the Goff lab archives:

Martinelli SC, Goff SP. Rapid reversion of a deletion mutation in Moloney murine leukemia virus by recombination with a closely related endogenous provirus. Virology. 1990 Jan;174(1):135-44.

Cheers,

Welkin

Stephen writes:

Greetings to the Fellowship of the Virus:

Thank you all for a wonderful and entertaining podcast. You all help make my 90-minute commute easier to handle. The weather in Pittsburgh this morning is unseasonably warm, 72 F (22 C) with a bunch of high, fair-weather clouds, and headed for 90 F (32 C). Hopefully autumn will return soon!

I enjoyed the lively discussion about plant-made polio vaccines in TWIV 459. I had an opportunity to tour the facility in North Carolina while I was a Master’s student in Biomanufacturing at NC State University. The company is called Medicago, and they are based out of Quebec City. This company produces biotherapeutics and vaccines using the same tobacco strains as mentioned in the episode. Medicago built their NC facility as part of DARPA’s pandemic flu vaccine challenge: make 10 million doses of a monovalent pandemic vaccine in less than three months. Using the plant method, they exceeded this goal by making more than the required 10 million doses. Since then, Medicago has been looking at other uses for their plant expression platform, including other vaccines (Rotavirus, HPV, Norwalk) and therapeutic proteins (antibodies against Ebola, biosimilars/biobetters).

I am also including a pick-of-the-week. I was browsing the literature when one of my lab mates handed me a copy of this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1311997/?page=1. I believe that this is one of the most concise papers I have ever read, and, like the reviewers, I find no flaws in the experimental design or results. Enjoy!

Peace and long life,

Stephen White

PhD Student in Molecular Biophysics and Structural Biology

University of Pittsburgh

Lab of Dr. Sanford Asher

Gary writes:

Hi Twiv gang,

I know that this is not the normal follow up but I was just wondering if any of you had heard from Tyler? I am not even sure if he was still on the island. I hope he was able to evacuate before the storm hit, and I hope that if he was not able to leave that someone has heard from him.

Do you know if he was still serving there? Do you know if the CDC moves people out in that type of situation? That storm was so very bad that I know that if he is still there he has probably lost everything. Maybe you would be able to find out if he needs any kind of assistance, and let us your audience know so that maybe we can send assistance in some way.

I just happened to be listening to the old show he was on a week or so ago and was not really thinking about hurricanes making the entire island near unlivable and now they are saying that not only are they short on water and food but they can’t even get diesel for the few generators they have there.

I know you don’t wanna talk about politics but that imbecile in the white house has really let the entire country down and in my mind has already killed so many because of his crap that I want to scream!

Anyway please update us as you find any information.

Michelle writes:

Dear TWiVers,

I’m writing about the use and misuse of the term ‘DNA’ that Vincent and Kathy railed against during the discussion on scientific publication readability (25th minute of TWiV 461). Hear, hear!

Last month I was excited about attending a book launch and seminar titled ‘Digital DNA’, only to find that ‘Digital DNA’ had nothing to do with actual DNA or genetic sequence data! It is apparently a term that has been co-opted to mean an organization’s corporate identity and is some sort of branding strategy (from what I can make out). The misuse of the term DNA is getting ridiculous!

This is my first time writing to TWiV but I’ve been listening religiously since 2011 when I was working towards my honors degree on intra-host genetic variation of Ross River virus. Unfortunately, a series of physical ailments took me out of the laboratory, but I loved the research process and viruses so much that I am now working on viruses and international law! I’m specifically researching virus ‘access and benefit-sharing’ (the legal term for a quid pro quo on genetic resources) and how treating viruses as commodities is likely to impact scientific research.

I’m from Brisbane, Australia where it is currently 17 degrees (Celsius, of course) and raining, but I’m currently writing from Washington, DC where it is 21 degrees and sunny.

I love the show; keep up the great work!

Kind regards,

Michelle

Johnye writes:

Merry  Holidays. There were other parodies of Christmas and holiday songs, but I feared some might think them offensive.

Enjoy!

My best to you and the star scientists who generously and faithfully instruct, inform and contribute to the greater good with each episode of “This Week in…” series of podcasts. Strength to all for the New Year, our shared birth date, and beyond.

Johnye Ballenger

https://youtu.be/DlzVp6g5e8o

https://youtu.be/0W9LLl3QPuM

https://youtu.be/iBsQOz5sGcg

Tom writes:

Dear Vincent & Crew,

The Central Texas noon weather headline for today, December 7th, reads “Few flurries today, then coldest night in 11 months.”  Currently it’s 45 F (7.2 C), 68% humidity, the dew point is 35 F, (1.66 C), the drizzle is letting up and we expect our first freeze of the season tonight.

I’ve got a listener pick, or maybe it’s a pick of a listener.

The recently released book “Soonish” has been in the news lately. Those who read the SMBC Web comic (www.smbc-comics.com) are probably familiar with husband-and-wife authors Zach and Kelly Weinersmith.

Zach is a full time cartoonist. Kelly is a parasitology researcher at Rice University (think Houston). Her most recent paper focused on how parasites control host behavior.

One of Zach’s recent SMBC comics (http://www.smbc-comics.com/comic/virus) had this dialog:

Him: “Do you think viruses are truly alive?”

Her: “Nah. They’re just barely getting by.”

The comic’s “hidden text” comment was, “If 8 percent of our DNA comes from viruses are we technically undead?”

I wrote to Zach and asked him if 1) Kelly listened to Vincent’s podcasts, and 2) if this comic was inspired by the TWiV crew kicking this question around. He responded that yes, Kelly did listen to the podcasts, but no, TWiV didn’t trigger this particular comic.

BTW, the Nov. 29 Freakonomics podcast made references to Soonish, and you can hear Kelly responding to their questions. Maybe you can get her on TWiP!

Does that count as a Pick of SMBC or of Kelly Weinersmith?

I know that XKCD has been a pick before, but I want to highlight three recent TWiX related entries:

https://xkcd.com/1895 ranked scientific fields along a line that represented “How worried you should be if you see local reporters interviewing scientists about a breaking news story.”  Virologist came in third most worrying, behind volcanologist and “Astronomer who studies the sun”.

https://xkcd.com/1904 had X/Y axes defining quadrants. The horizontal low-to-high axis represented “Risk of the thing you’re studying breaking free from your facility and threatening the local population” and the vertical low-to-high axis represented “Risk of your research being used by a supervillain for world domination”. Genetic Engineering and Microbiology were the most extreme in the high/high quadrant.

https://xkcd.com/1923 shows a thermometer above the following caption: “Since the Celsius vs Fahrenheit debate has proven surprisingly hard to resolve, as a compromise I’ve started using Felsius (e) the average of the two.”  (Conversion formulas appear in the picture.)

– Tom in Austin

P.S.

A more recent XKCD noted that “The moon’s craters and plains are the only structures on the surface of a celestial body that can be seen with the naked eye from the Great Wall of China.”

Vincent Racaniello

Vincent Racaniello, Ph.D. is Professor of Microbiology at Columbia University Medical Center. As principal investigator of his laboratory, he oversees the research that is carried out by Ph.D. students and postdoctoral fellows. He also teaches virology to graduate students, as well as medical, dental, and nursing students.

Vincent entered the world of social media in 2004 with virology blog, followed by This Week in Virology. Videocasts of lectures from his undergraduate virology course are on iTunes University and virology blog. You can find him on WikipediaTwitter, Facebook, and Instagram. His goal is to be Earth’s virology professor. In recognition of his contribution to microbiology education, he was awarded the Peter Wildy Prize for Microbiology Education by the Society for General Microbiology. His Wildy Lecture provides an overview of how he uses social media for science communication.

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