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BarneyGrahamMD's profile
Barney Graham, MD, PhD
Barney Graham, MD, PhD
Barney Graham, MD, PhD
@BarneyGrahamMD

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Barney Graham, MD, PhD

@BarneyGrahamMD

Physician, Scientist, Vaccinologist, #MedTwitter. Coronavirus, Influenza, RSV, + Emerging Virus Vaccine Development. Pandemic Preparedness. Social Justice.

Atlanta, GA
niaid.nih.gov/research/barne…
Joined March 2020

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    1. Barney Graham, MD, PhD‏ @BarneyGrahamMD 13 Jan 2021

      Having a pre-established public-private relationship and a high level of trust and confidence between partners was an important factor for making quick decisions needed to achieve rapid vaccine development in the midst of a pandemic.

      2 replies 9 retweets 90 likes
      Show this thread
    2. Barney Graham, MD, PhD‏ @BarneyGrahamMD 14 Jan 2021

      VRC & Moderna began collaborating in 2016 during the Zika PHEIC and directly compared our DNA vaccine to their mRNA vaccine using similar antigen constructs. We then started a pandemic preparedness project based on prototype pathogens in 2017.

      3 replies 8 retweets 64 likes
      Show this thread
    3. Barney Graham, MD, PhD‏ @BarneyGrahamMD 14 Jan 2021

      1/13/20 was also the first day of a large international meeting in Bethesda to discuss Bunyaviruses, another pandemic threat. It was part of an overall effort to define prototype viral pathogens for each of the 26 viral families that infect humans.

      1 reply 6 retweets 56 likes
      Show this thread
    4. Barney Graham, MD, PhD‏ @BarneyGrahamMD 15 Jan 2021

      We designed vaccines for Nipah and MERS-CoV to represent paramyxoviruses and coronaviruses and had already tested mRNA vaccines for these 2 viruses in animal models in 2019 with good results and planned to do a clinical trial with Nipah mRNA vaccine.

      2 replies 7 retweets 59 likes
      Show this thread
    5. Barney Graham, MD, PhD‏ @BarneyGrahamMD 15 Jan 2021

      On 1/7/20 VRC to Moderna, “If it’s a SARS-like CoV we know what to do and have proven that mRNA is effective at a very low dose. … this would be a great time to run the drill for how quickly can you have a scalable vaccine.”

      4 replies 10 retweets 96 likes
      Show this thread
    6. Barney Graham, MD, PhD‏ @BarneyGrahamMD 16 Jan 2021

      1/15/20 was the day that VRC investigators decided that SARS-CoV-2 vaccine evaluation needed to be done in collaboration with a broad coalition of NIAID divisions, academic groups, and government agencies. We did Zika vaccine development independently.

      2 replies 3 retweets 41 likes
      Show this thread
    7. Barney Graham, MD, PhD‏ @BarneyGrahamMD 16 Jan 2021

      Even though the VRC is self-contained in the sense of having basic research, translational science, animal modeling, process development, pilot manufacturing, and clinical evaluation capabilities, we were not able to advance the Zika DNA vaccine beyond phase 2b.

      4 replies 2 retweets 36 likes
      Show this thread
    8. Barney Graham, MD, PhD‏ @BarneyGrahamMD 16 Jan 2021

      As wisely noted in the African proverb, “if you want to go fast, go alone, but if you want to go far, go together.”  This has been well illustrated in the COVID-19 vaccine development process.

      5 replies 39 retweets 221 likes
      Show this thread
    9. Barney Graham, MD, PhD‏ @BarneyGrahamMD 23 Jan 2021

      Since 1/11/2020 we were waiting for the Genscript plasmids to come back. They will come tomorrow. At this time last year there was only a few dozen cases reported in China and Hong Kong, but we were committed to rapid demonstration project for pandemic response.

      1 reply 2 retweets 49 likes
      Show this thread
    10. Barney Graham, MD, PhD‏ @BarneyGrahamMD 23 Jan 2021

      We were fortunate to have made GenScript order on Sat. the 11th because by Mon. there was a queue resulting in large backlog & delayed orders. For past 10 days we had been gathering reagents/supplies and planning timelines and the order of activities to avoid gaps in progress

      3 replies 3 retweets 72 likes
      Show this thread
      Barney Graham, MD, PhD‏ @BarneyGrahamMD 24 Jan 2021

      January 24th, 2020 was the day we received the plasmids we needed to start making the spike protein which is the basis for everything related to vaccine development. Dr. Corbett @KizzyPhD was ready to get started.pic.twitter.com/sX7vn0OR7O

      2:01 PM - 24 Jan 2021
      • 172 Retweets
      • 1,052 Likes
      • Alejandro Nesha, MS Jim Revkin Binoy Mathew Theresa Bruce Hassa2 Maedot ማዕዶት M🇪🇹 🇫🇮 unapologetically Ethiopian! Nasty Woman mom21
      11 replies 172 retweets 1,052 likes
        1. New conversation
        2. Barney Graham, MD, PhD‏ @BarneyGrahamMD 26 Jan 2021

          I’m going to introduce you to some of the students who helped do some of the lab work as we started making protein and developing assays to measure antibody responses. This is Olu Abiona, headed to an MD, PhD program.pic.twitter.com/p8IJNoTaMk

          4 replies 12 retweets 148 likes
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        3. Barney Graham, MD, PhD‏ @BarneyGrahamMD 26 Jan 2021

          This is Cynthia Ziwawo who is now a medical student. Her specialty was the ELISA that we used to measure antibody responses.pic.twitter.com/6Tdo5qngcm

          4 replies 11 retweets 165 likes
          Show this thread
        4. Barney Graham, MD, PhD‏ @BarneyGrahamMD 26 Jan 2021

          Geoffrey Hutchinson is now a graduate student continuing his work on vaccine design. He was a big part of the team in those early days.pic.twitter.com/eOeZCbpguX

          4 replies 7 retweets 129 likes
          Show this thread
        5. Barney Graham, MD, PhD‏ @BarneyGrahamMD 30 Jan 2021

          One year ago today I was in Barcelona giving a talk at the childhood pneumonia meeting while the team I introduced was making our first batch of nCoV spike protein. The virus was called novel coronavirus before it was called SARS-CoV-2.pic.twitter.com/tiDezkjbxD

          2 replies 8 retweets 56 likes
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        6. Barney Graham, MD, PhD‏ @BarneyGrahamMD 30 Jan 2021

          A few days earlier we were scrambling to find enough media to do the transfections. One part of the VRC had to borrow from another as supplies were backordered, but no days were lost. All hands on deck.pic.twitter.com/xtFoRsejTx

          2 replies 2 retweets 56 likes
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        7. Barney Graham, MD, PhD‏ @BarneyGrahamMD 30 Jan 2021

          The result of all the effort to advance the project without wasting any days resulted in eluting our first batch of nCoV spike protein on Jan. 30, 2020. We immediately sent protein and plasmids to CDC and to other collaborators. Dr. Fauci mentioned our work at ASM Biothreats mtg.pic.twitter.com/yj326e9z2e

          3 replies 4 retweets 65 likes
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        8. Barney Graham, MD, PhD‏ @BarneyGrahamMD 31 Jan 2021

          On Jan 31st, 2020 I was headed back to the airport after the childhood pneumonia meeting and checked in with Jason McLellan @McLellan_Lab He and Daniel Wrapp had already obtained preliminary data on the nCoV spike structure in just 20 days from the time of sequence posting.pic.twitter.com/qzUYbrt9A0

          2 replies 7 retweets 80 likes
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        9. Barney Graham, MD, PhD‏ @BarneyGrahamMD 31 Jan 2021

          The first atomic level crystal structure of a virus glycoprotein (influenza hemagglutinin) was published by Ian Wison, John Skehel, and Don Wiley in Nature Jan 29, 1981. We are just passing the 40th anniversary of that event. HA is another class 1 fusion protein like CoV spike.

          1 reply 4 retweets 83 likes
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        10. Barney Graham, MD, PhD‏ @BarneyGrahamMD 6 Feb 2021

          On Feb 2, 2021 I got an email from Ugur Sahin from BioNtech who wanted to talk about vaccine antigen designs. I called and told him about our work on spike structure and stabilization and expression of trimeric antigens by gene-based delivery.

          4 replies 3 retweets 55 likes
          Show this thread
        11. Barney Graham, MD, PhD‏ @BarneyGrahamMD 6 Feb 2021

          I meant to add that on Feb 1 we used the protein first made on Jan 31 to test an ELISA. This is a method for measuring antibody. The protein is put on the bottom of each well then serum dilutions are added. More yellow means more antibody. You can see color changes with dilutions

          3 replies 0 retweets 28 likes
          Show this thread
        12. Barney Graham, MD, PhD‏ @BarneyGrahamMD 6 Feb 2021

          Feb 3,2020 Jason and Daniel Wrapp @McLellan_Lab had refined the structure and we started writing the paper. Knowing protein is in the right conformation is what gives the confidence to construct diagnostics, make reagents for mAb discovery, and make vaccines.

          1 reply 1 retweet 36 likes
          Show this thread
        13. Barney Graham, MD, PhD‏ @BarneyGrahamMD 6 Feb 2021

          Feb 4, 2020 was a big day. Several hundred mice were immunized with nCoV spike protein and the first research grade batch of mRNA-1273 expressing stabilized spike. Multiple dose levels & mouse strains used. Starting multiple groups gave flexibility for later experimental choices.

          3 replies 4 retweets 43 likes
          Show this thread
        14. Barney Graham, MD, PhD‏ @BarneyGrahamMD 6 Feb 2021

          I’m out of practice. Here are the ELISA plates that go with Feb 1, 2020 comment. Also, since I can’t edit, the year for the Feb 2 comment was written 2021 and should have been 2020.pic.twitter.com/mOT3EoBtQ0

          3 replies 0 retweets 38 likes
          Show this thread
        15. Barney Graham, MD, PhD‏ @BarneyGrahamMD 9 Feb 2021

          I’m going to review the connections between respiratory syncytial virus work over last few decades and current coronavirus vaccines. To put into context, RSV was discovered in 1956 and there are <20K scientific papers in the entire field. There are ~100K COVID papers in 1 yr.

          2 replies 6 retweets 44 likes
          Show this thread
        16. Barney Graham, MD, PhD‏ @BarneyGrahamMD 9 Feb 2021

          RSV is in Pneumovirus family. Used to be a paramyxovirus. Both are enveloped RNA viruses. They have a fusion (F) protein that is analogous to Spike protein on CoV. F rearranges to pull cell membrane into virus and fuse so virus genome can get in cell to start replicating.

          2 replies 0 retweets 36 likes
          Show this thread
        17. Barney Graham, MD, PhD‏ @BarneyGrahamMD 18 Feb 2021

          This was a big day one year ago. We immunized mice with mRNA-1273 on Feb 4th and collected serum 14 days later. You often don’t see much antibody response this soon after single dose and that’s why you typically need a second dose. This would be first indication of immunogenicity

          3 replies 9 retweets 69 likes
          Show this thread
        18. Barney Graham, MD, PhD‏ @BarneyGrahamMD 18 Feb 2021

          In this case, the ELISA plates turned bright yellow almost instantly meaning there was a strong antibody response to single 1 ug mRNA injection. We were still building virus to measure neutralizing activity, but seeing this was an indication we were making spike-binding antibody.

          2 replies 3 retweets 82 likes
          Show this thread
        19. Barney Graham, MD, PhD‏ @BarneyGrahamMD 12 Mar 2021

          March 11 was one year anniversary of the WHO declaration that COVID-19 was a pandemic disease and beginning of lockdown in the US. We were just a few days away from starting phase 1 study, which began as a demonstration project but now became an advanced development program.

          1 reply 10 retweets 80 likes
          Show this thread
        20. Barney Graham, MD, PhD‏ @BarneyGrahamMD 12 Mar 2021

          We had reached several milestones by this point last year. The paper describing the structure of the nCoV (I.e. SARS-CoV-2) spike went online 2/19/20. This was critical, because we had no mAb reagents yet other than what we had made from SARS-1 survivor PBMCs apheresed in 2018.

          1 reply 4 retweets 20 likes
          Show this thread
        21. Barney Graham, MD, PhD‏ @BarneyGrahamMD 12 Mar 2021

          Knowing the spike protein was in the right conformation gave us confidence to develop ELISA and NT assays, make probes for mAb discovery, and proceed with vaccine development despite not having the usual reagents to characterize the authenticity of the structure.

          4 replies 0 retweets 20 likes
          Show this thread
        22. Barney Graham, MD, PhD‏ @BarneyGrahamMD 12 Mar 2021

          I’m breaking my daughters 3 tweet per day rule because I got behind on the story over the last 3 weeks. Another milestone was Abcellera starting sorting survivor PBMCs on 2/27/21 with the spike probes we sent with the cells. A bonus or byproduct of the new vaccine technologies.

          3 replies 0 retweets 38 likes
          Show this thread
        23. Barney Graham, MD, PhD‏ @BarneyGrahamMD 12 Mar 2021

          By this week last year we had a working version of pseudovirus NT assay and obtained mouse sera from 2w post 2nd dose. At the time, what seemed like striking levels of neutralizing activity had been induced by mRNA-1273 which was important for me to see before starting phase 1.

          2 replies 2 retweets 48 likes
          Show this thread
        24. Barney Graham, MD, PhD‏ @BarneyGrahamMD 15 Mar 2021

          In the days prior to the start of the mRNA-1273 phase 1 last year we were frantically trying to keep up with requests for spike protein and plasmids and were shipping reagents all over the world. We were also trying to connect people with adjuvants to other groups with proteins.

          2 replies 0 retweets 21 likes
          Show this thread
        25. Barney Graham, MD, PhD‏ @BarneyGrahamMD 15 Mar 2021

          We were setting up shipments to have immunized mice challenged with Ralph Baric’s mouse-adapted virus and beginning NHP studies. Calls from collaborators & journalists flooding in and we were trying to cope with limited access of personnel to bench space because of lockdown.

          5 replies 2 retweets 27 likes
          Show this thread
        26. Barney Graham, MD, PhD‏ @BarneyGrahamMD 15 Mar 2021

          Importantly, we had already shipped spike probes and PBMCs to Abcellera and they had sequenced sorted B cells and selected antibodies that we had screened and already identified potent neutralizing mAbs. When Lilly got involved, manufacturing and clinical development sped up.

          3 replies 0 retweets 34 likes
          Show this thread
        27. Barney Graham, MD, PhD‏ @BarneyGrahamMD 16 Mar 2021

          One year ago (3/16/20) that Moderna Phase 1 started at the Kaiser Permanente Clinic in Seattle. COVID-19 had just begun spreading in US especially in Seattle. This created an unexpected complication for conducting trials while keeping staff and subjects safe and out of quarantine

          2 replies 2 retweets 56 likes
          Show this thread
        28. Barney Graham, MD, PhD‏ @BarneyGrahamMD 9 May 2021

          1 year ago today is when I first knew the vaccine was likely to work. Those first 8 subjects were boosted with 2nd dose on April 13th and on 4/27/20 serum was obtained. We had shown antibody responses occurred even after 1st dose, but still had not measured neutralizing activity.

          5 replies 10 retweets 55 likes
          Show this thread
        29. Barney Graham, MD, PhD‏ @BarneyGrahamMD 9 May 2021

          On May 9, 2020 I got a call from Jim Chappel and Mark Denison at Vanderbilt. They had been measuring neutralizing activity of vaccinee serum against live SARS-CoV-2 in their BL3 lab. They described the results and then showed me the curves. The potency was better than expected.

          1 reply 2 retweets 32 likes
          Show this thread
        30. Barney Graham, MD, PhD‏ @BarneyGrahamMD 9 May 2021

          Neutralization means that something can prevent virus infection of cells. This usually is based on serum antibodies that block attachment or interfere with protein rearrangement required for membrane fusion. The measurement is done by exposing virus to a range of serum dilutions.

          1 reply 2 retweets 14 likes
          Show this thread
        31. Barney Graham, MD, PhD‏ @BarneyGrahamMD 9 May 2021

          The neutralizing curve created by plotting serum dilutions against reduction of virus infection has several important features. It makes a sigmoid, S-shaped curve. It is usually reported as the dilution that caused 50% or 80% reduction. Having a steep slope in the curve is good.

          1 reply 2 retweets 12 likes
          Show this thread
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