TWiV 931: Driven to immunodistraction

August 28, 2022

TWiV reviews the genetic characterization of a new strain of type 2 oral polio vaccine and its implications for eradication, and how a polymorphism in humans comprising a single amino acid change in an antibody molecule regulates vaccine elicitation of broadly neutralizing antibodies against influenza virus HA.

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Kathy Spindler, and Brianne Barker

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Download TWiV 931 (73 MB .mp3, 121 min)
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Intro music is by Ronald Jenkees

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3 comments on “TWiV 931: Driven to immunodistraction

  1. portia Sep 11, 2022

    Hi, dear Vincent et al,
    I have been a listener since early 2021. Most times I agree with you, but we differ in view on whether we should get more boosters to the COVID vaccines, but never mind that, I went to get my 5th shot yesterday, and I asked the pharmacist if they have any recommendations as to which arm we should get the booster in, She said there are no recommendations, but I remember hearing on TwiV about the germinal. centers proximity and that it would be good to get it in the same arm, so I did. But I wonder how well known this information is and if it should be better known to all.
    Thanks for the wonderful work you and your team do.


  2. Ed Kisailus Sep 17, 2022

    Hello Twiv, I’ve been listening now to TWIV going on six months. To say how informative the programs are to scientists and non-scientists alike would be an understatement. Thank you team, including Daniel Griffin’s clinical update, for a most informative podcast.
    I heard the TWIV team reminisce about Dr. Kabat on TWIV 931. I am a Columbia grad, GSAS ’77, from the Department of Microbiology. I did my Ph.D. research in Dr. Elvin Kabat’s lab on competitive binding assays for blood group substances A1 and A2 as my major research project, (Kisailus EC, Kabat EA. Immunochemical studies on blood groups LXVI. Competitive binding assays of A1 and A2 blood group substances with insolubilized anti-A serum and insolubilized A agglutinin from Dolichos biflorus. J Exp Med. 1978 Mar 1;147(3):830-43. doi: 10.1084/jem.147.3.830. PMID: 75942; PMCID: PMC2184207.).
    I find the “banter” about virology and immunology to be most informative as the recall of past scientists and their discoveries does put current research into perspective. I am pleased to add to the conversation about Dr. Kabat, and his research on the hypervariable regions aka CDRs. This research was indeed groundbreaking and opened immunology to understanding heterogeneity and specificity of the immune response.
    The hypervariable region research began, as he related to us, in his apartment on Haven Avenue where he would write the sequences of the variable regions on strips of paper, lay them out on the floor and maximize them for homology of sequence. The idea of hypervariable regions then moved to collaboration with Dr. Tai Te Wu of Northwestern University and using computer analysis began the seminal work on antigen-contacting regions and residues. The NIH work with Dr. Wu and Dr. Howard Bilofsky generated the books of sequences before they were uploaded to the internet, kept to date and expanded to other immunological molecules on KabatMan. Dr. Kabat gave me an autographed first volume on the day I defended my Ph.D. thesis, June 24, 1977.
    Yes, as the team discussed Dr. Kabat did inject himself with antigen. My experience was watching a post-doc draw 50cc of blood for research on anti-dextran antibodies. If my recall is accurate it was Dr. Kabat’s dextran antibodies that were used to determine the size of the antibody combining site. In addition, there was antisera in the lab to blood group substances derived from injecting medical students as far back as the 1950s. Pneumococcal polysaccharide antibodies too were derived in a similar fashion by injecting medical students. Avery OT, Heidelberger M. IMMUNOLOGICAL RELATIONSHIPS OF CELL CONSTITUENTS OF PNEUMOCOCCUS : SECOND PAPER. J Exp Med. 1925 Aug 31;42(3):367-76. doi: 10.1084/jem.42.3.367. PMID: 19869059; PMCID: PMC2131014. In my research I did use some of the blood group substance, and pneumococcus polysaccharide antisera, kept in the cold room (never frozen) and preserved with a few drops of phenol.

    As a mentor Dr. Kabat was tough but fair. As a mentor his research and knowledge laying down the foundations of immunochemistry and immunology serves me to this day. When I reflect on some of my early ideas for experiments which he would rightly nix as they were not thought through. My assigned time for the weekly one-on-one, go ever the data meetings was each Wednesday at 6:30 am. As I progressed in my research the meetings became real thoughtful discussions.
    As a mentor he was bar none tough but fair. Structural Concepts was a must read and required to be thoroughly digested. Experimental Immunochemistry sets on my bookshelf as I write. Lab started at 8:00 am and we would be expected to work on our projects until 5:00. I had five projects going over the three years I was in the lab, with three published. Dr. Kabat was in the lab by 5:30 am and left at 5:00 pm each day. Individual lab meetings, as I mentioned above mine were at 6:30 on Wednesdays, meant that you always had data to discuss and more importantly plans for the next steps, and ideas to troubleshoot pitfalls.
    There are so many “stories” about the lab that I could recount but snapshot encounters or occasional meetings with Dr. Kabat belies the man and the atmosphere he promoted in the lab. We were more of a family with the post-docs (six at one time in my three years there), three pre-docs, two technicians, two glassware washers, a secretary and an occasional three-month rotation student. We’d hang out together on weekends exploring sights and sounds of New York. On occasion Dr. Kabat would invite the lab to his apartment for a get together, and conversation; and had each one of us sign his guest book. Mrs. Kabat (Sally), his wife, remembered each of us with a gift at Christmas time. Dr. Kabat kept us informed of his research at NIH, and would recount some history about his career, e.g., his work with Tiselius and Svedberg, issues emanating from his work in the Manhattan Project, to name but a few. One memorable time he came into the lab all excited holding an aluminum wire, variable region, antibody combining site designed from X-Ray crystallographic data. The site was of the dextran antibody and he had us all put or hand into the site to observe the CDRs (contact determining residues). He never missed a chance to educate us and keep us current in the field. Scientists often came to visit him and he would bring them into the lab where each of us were introduced, pre- and post-docs alike, and would talk about and explain our research. A memorable conversation I had about my work is when Dr. Baruj Benaceraf visited.
    Your TWIV group paper discussions also brings to mind Dr. Kabat’s Saturday morning, 8 -11, seminars where vigorous discussions (banter) would occupy the morning. You had better be prepared to defend to Dr. Kabat and the post-docs and pre-docs there why you chose the five papers. You summarized a paper and it would either be summarily dismissed by Dr. Kabat to be out of date or of little or no importance to the group; or if the work was important you reported in detail on the research (as you do on TWIV). These seminars even occurred when Dr. Kabat was a Fogarty scholar at NIH when he would leave right after seminar for Bethesda and be back in the lab the following Wednesday morning.
    I began my research education with Dr. Erlanger, also the grad advisor, who took me into his lab to work for the summer before my first set of classes began in September 1972. There I isolated nucleosidyl transferase from M. lysodeikticus. That counted as one of my three rotations. My second three-month rotation was with Dr. Rosenkranz where I “cut my teeth” on EM of HSV, and the third rotation with Dr. Kabat, where I was handed a gallon of ovarian cyst fluid, sent by Ada Bezer, to isolate blood group substance. Two lab technicians, Jerry and Pabing taught all the techniques and how to be analytically precise to meet Dr. Kabat’s standard. Our lab notebooks were to be a precise description of each experiment to the point where anyone reading them would know exactly how the experiment(s) were carried out. Precision and analytical accuracy were first and foremost in the lab. Lazy notetaking was not tolerated, and rightly so. All lab notebooks were sewn bound so no pages were to be removed just X’d through if there was a do over experiment. The notebooks were left with the lab after we left.
    I did go on after Columbia to a 40+ year career of undergraduate teaching at Canisius College in Buffalo, NY. Interestingly Dr. Erlanger was influential in my career choice; and Dr. Kabat was very supportive. Dr. Kabat gave us the education to be successful after Columbia. For this I will always be grateful
    Thanks for reading my email, and for what you do on TWIV (and
    Edward C. Kisailus, Ph.D.
    Professor Emeritus, Department of Biology
    Canisius College, Buffalo NY

    PS: I have an appreciation for the TWIV discussions on poliovirus as it reminded me of my virology class with Dr. James Darnell. I recall many papers read on poliovirus; and Dr. Darnell’s contribution to discovering the polyA tail. That class was held at the 116th street campus while all the other classes were either at P&S, the Black Building, or at the time the newly built Armand Hammer building.