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The Phat version of “The Skinny” Thinking Out Loud Blog

This is truly Phat – we are taking action to keep your inbox thinner! In the latest Thinking Out Loud newsletter, I promised to share my COVID cooking obsession and some ideas about the balance between immunogenicity and tolerance.  

Food First! During COVID, I have been learning about roasting vegetables from Ottolenghi. His most recent cookbook, Flavor, was a holiday present. After opening it, I just had to sit down with a stack of sticky notes, and I ended up flagging nearly every page. Over the past 9 months, I’ve tried nearly every recipe. If you want to know more about his amazing plant-based cooking, read: Epicurious. Or just check out the recipes on the NYT Cooking Page.

Flavor is about roasting, which totally changes the way vegetables taste. Roasted celeriac (celery root) done the Ottolenghi way is amazing –  roasted at 450 degrees °F and basted in olive oil and salt, then cut in thin wedge-shaped slices, add yogurt and tahini dressing and Yum! In addition to celeriac, I have roasted carrots (see pre-photo below), eggplant, zucchini, and beets. And all of the recipes are plant-based! I’m not done trying the recipes, nearly a year later. My family thinks that I have gone insane.

Next – the Yin and Yang of Proteins

Maybe it was the rosé wine, but I had a great conversation with Eric Harvill and Justin Bahl in Athens, Georgia over dinner recently, about protein structure and function. Perhaps they were just putting up with me, but the conversation went something like this: if proteins had not “learned” to survive inside of our bodies, would we be here today?

When you think about it, proteins have to function in really hostile environments. All kinds of forces are at work to degrade, interfere with, and clear proteins. Making proteins is energy intensive, and a protein that does not function and becomes the target of an immune response or protease that eliminates the protein, is not worth the energy we expend to create them. Thus, in addition to encoding features that allow proteins to avoid degradation proteins introduce post-translational modifications  (by cooperating with enzymes) to create features that preserve their structure. Looking at pathogens, we find that they have evolved a range of defense strategies to avoid elimination by the immune system, so why wouldn’t “self” proteins have similar strategies?

So here goes: Our hypothesis is that proteins have, over evolutionary time, both deleted T cell epitopes that could trigger immunogenicity and have also encoded “off switches” for immune response for “immunological survival”. In our paper on the iVAX platform for vaccine design, we uncovered an analysis performed by Andres Guiterrez at EpiVax that showed that host proteins have fewer T cell epitopes than would be expected by random chance, and that common, circulating “secreted” proteins in the human proteome have even fewer T cell epitopes.

Travels with Katie

We’re getting back in the swing of things! But first – what’s the new COVID etiquette! Do you fist bump? Hug? Air kiss? Myself, Katie Porter, and the rest of the BD team are getting back to in-person meetings and events, how about you? Masks really do interfere with communication, so #VaccinesRock! We are beginning to plan our travels and already thinking ahead to booking at our favorite restaurants (OK, returning to our favorite theme, good food!). We look forward to seeing you in person, in the places we love even more (Tokyo! Amsterdam! Barcelona!).

Here are some of our favorite restaurants in our favorite cities:

 

Have a favorite restaurant? Send us your suggestions for our travels!

And when you see us – if you are vaccinated, give us a hug!

Well yes, we can (meet in person and hug)! I gave two talks at TIDES Boston 2021our first in-person conference in 18 months – one on immunogenicity of generic synthetic peptide impurities and one on our COVID-19 vaccine. I can share the recordings with individuals that are interested, just let me know! EpiVax Therapeutics CSO Mike Princiotta gave a great talk on our personalized cancer vaccine programEfficient Selection of tumor antigens in the design of Personalized Cancer vaccines” at the International Society for Vaccines Annual Congress earlier this month. Do NOT miss this great presentation of our work on cancer vaccines, and his explanation of the importance of stimulating effective T cell responses as an adjunct to cancer immunotherapy. His presentation is crisp and it presents the scientific rationale for using Ancer, the tool Bill Martin, Matt Ardito and Guilhem Richard at EpiVax built for personalized cancer vaccines.

We had a reception at Legal Seafoods. Yum! Katie Porter and Brian Roberts, long time EpiVaxers, look fabulous in the Legal Space next to Boston Harbor, and you can enjoy your first glimpse of our new team members Riley Nolan (L) and Nicole Ruggiero (R, COO of EpiVax Therapeutics) below! Of course, being outside reduces concern about COVID, but what we didn’t know ahead of time was that we were right next to an outdoor concert featuring Alice Cooper! On the night of our reception. That kept things quite lively! More pictures of our guests are below.

And . . . Getting on the Road Again

Coming up next? AAPS PharmSci360 (see you in Philly!) where I will be talking about improving on nature in the design of protein therapeutics, and the EpiVax Amsterdam Immunogenicity & Seminar (In Europe? Join us!). We are getting back in the swing!

Check out the EpiVax talks at AAPS PharmSci360:

Annie De Groot

Speaker Spotlight: Engineering Better Biologics: Does Nature Know Best?

Monday, October 18, 2021

3:30 PM – 4:30 PM ET

 

Amy Rosenberg

Prologue: Optimizing Patient Outcome with Prevention and Mitigation Strategies for Immunogenicity of Therapeutic Proteins

On-Demand

 

Preparing for Success: Risk Assessment and Mitigation of Immunogenicity During Developability of Biologics

Wednesday, October 20, 2021

10:00 AM – 10:20 AM ET

 

Panel Discussion

Wednesday, October 20, 2021

10:40 AM – 11:00 AM ET