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Peter Attia MDPeter Attia MD

#115–David Watkins, PhD: Immunology, monoclonal antibodies, & vaccine strategies for COVID-19

Original release date: 6/15/20 In this episode, David Watkins, professor of pathology at George Washington University, shares how insights from his HIV and Zika virus research could apply to SARS-CoV-2 protection strategies. David introduces monoclonal antibodies as an intervention to prevent and treat COVID-19 infection, and also discusses how they could be used as a hedge to vaccine development. Additionally, David’s immunology tutorial explains the innate and adaptive immune systems and their differentiated responses to viral infection. We discuss: 00:00:00 - Intro 00:04:30 - Background and current interest in immunology 00:10:15 - Immunology 101—The innate and adaptive immune system 00:19:00 - Defining antibodies, importance of neutralizing antibodies, and serology testing for COVID-19 00:25:00 - B cells—How they fight viruses, create antibodies, and fit into the vaccine strategy 00:36:15 - T cells—Role in the adaptive immune system and ability to kill infected cells to prevent viral spread 00:51:00 - Valuable lessons from HIV applied to SARS-CoV-2 01:01:30 - Lessons to be taken from the hepatitis C success story 01:04:45 - Monoclonal antibodies, vaccines, and the most promising strategy for preventing and treating COVID-19 infection 01:19:00 - COVID-19 vaccines in development 01:25:20 - How David’s work with Zika virus informs his thinking on SARS-CoV-2 01:27:45 - Why a vaccine for COVID-19 doesn’t need to be perfect to be effective Show notes page: https://peterattiamd.com/davidwatkins/ About: The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 30 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more. Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life). Learn more: https://peterattiamd.com/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Play: http://bit.ly/TheDriveGooglePlay

Peter AttiahostDavid Watkinsguest
Jul 9, 20201h 37mWatch on YouTube ↗

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At a glance

WHAT IT’S REALLY ABOUT

David Watkins explains immunology, neutralizing antibodies, and monoclonal antibodies for fighting COVID-19

  1. Watkins walks through the innate and adaptive immune systems, describing how B cells affinity-mature antibodies and how CD8 killer T cells destroy infected cells that antibodies cannot reach.
  2. He stresses that standard serology tests measure antibody binding, not neutralization, citing a not-yet-published Rockefeller study in which almost 20% of seropositive people made no neutralizing antibodies.
  3. Lessons from HIV, whose variability, chronic nature and sugar-shielded envelope have defeated vaccine efforts, and from the drug-based cure for hepatitis C show that science can find solutions without a vaccine.
  4. Watkins calls monoclonal antibodies cloned from the best human responders the most exciting hope for preventing and treating COVID-19, especially for the elderly who respond poorly to vaccines.
  5. He and Attia argue a COVID-19 vaccine need not be perfect, since lowering viral load can reduce symptoms, ICU admissions and transmission, and they stress that human data trumps animal data.

IDEAS WORTH REMEMBERING

5 ideas

Antibody tests do not show neutralizing ability

Watkins says common IgG/IgM tests measure antibody bound to a piece of virus, not whether it blocks infection. Neutralization requires a difficult lab assay that mixes serum with live virus and cells.

People vary widely in making neutralizing antibodies

In the Rockefeller study Watkins cited, almost 20% of about 70 people made none, and titers ranged from roughly 1-in-100 to 1-in-5,000 dilutions. Whether this affects reinfection risk is unknown.

B cells and T cells play complementary roles

Antibodies block virus from entering cells, but once a cell is infected only CD8 T cells can recognize pieces of virus displayed on MHC and kill the cell. Both arms, helped by CD4 cells, are needed.

HIV is uniquely hard to vaccinate against

Watkins cites enormous variability, chronic infection, few envelope copies covered in sugar, and the fact that no vaccine has induced neutralizing antibodies against it. Effective drugs and PrEP controlled it instead.

Monoclonal antibodies may be the future of infectious disease prevention and treatment

Antibodies cloned from super-responders can be engineered to last three to six months and given to vulnerable people. Watkins notes Ebola monoclonal treatment dropped death rates from about 50% to about 15%.

WORDS WORTH SAVING

5 quotes

So I like to think of a infected cell as a virus factory. You need to shut that virus factory down.

— David Watkins

So these buckets full of pieces of HIV are like flags on the surface of an infected cell that say, "Kill me, because if you don't, I'm gonna release a thousand or two virus particles into the infected person's blood."

— David Watkins

I think every virus presents its own particular set of challenges, and HIV presented us as vaccinologists with a set of challenges which I think frankly are going to be insurmountable.

— David Watkins

But for me, the most exciting hope that we have for treating this virus is neutralizing antibodies delivered as monoclonal antibodies.

— David Watkins

As I age, I think the message is, "Guys, try everything that you can. We need everybody's approaches, and one of them is going to work better than another, but we need a combination of all of these approaches."

— David Watkins

Innate versus adaptive immunityB cells and affinity maturationNeutralizing antibodies versus serology testsCD8 T cells killing infected cellsHIV and hepatitis C lessonsMonoclonal antibodies as the new vaccinologyCOVID-19 vaccine approaches and goals

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