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Expert Interview

Slingshot members are talking to an expert! The topic is:

A look into the proposed mRNA-based vaccine for the prevention of Shingles

Ticker(s): BNTX, PFE

Who's the expert?

Institution: Fred Hutchinson Cancer Center

  • Infectious disease physician and researcher who develops mathematical models to address significant medical challenges, assess the potential of a wide variety of potential curative technologies, explain when and how latent viruses reactivate and use models to optimize the effectiveness of antiviral drugs.
  • Major focus of his work is to analyze strategies to achieve an HIV cure and study how T cells help control numerous herpes viruses that cause disease in healthy people and in cancer patients with compromised immune systems.
  • His team also focuses on COVID-19, including developing models of the immune response against the coronavirus and the best treatment strategies

Interview Questions
Q1.

Please describe your professional background and details about your clinical practice

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Q2.

Could you talk a little bit about Shingles and how this affects people

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Q3.

In terms of Shingles vaccines, is this vaccination something you recommend for all adults above 50, and is Shingrix now the standard here? Are there other options that compete with it, or only older products that are considered inferior?

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Q4.

---What are the limitations of Shingrix or other shingles vaccines currently available? What is the unmet need or additional need here that can be addressed by a new product?

And based on those limitations how might a new option be a welcome entrant to the marketplace?  Or is there no such need that you see?

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Q5.

Does the protection from Shingrix last?  Or does it wear off, and if so after how long?

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Q6.

---mRNA vaccines against Covid-19 exhibited waning immunity over time. Is this a concern for an mRNA approach to Shingles, or does the virus lack the evolution ability that coronavirus has to evade immunity over time?

What is happening with the virus while it sits latent in the body? Is it mutating and evolving, or only once it starts replicating after reactivating?   How does it reactivate, and how does the evasion of immunity work?  (for example, from Shingrix) 

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Q7.

How might an mRNA approach work for varicella zoster virus, or why might it not work based on what you know about the virus?

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Q8.

--- I read that Shingrix produces a robust T cell response. Is this correct in your view?

Would an mRNA approach produce a sufficient T cell response to match the kind of efficacy Shingrix achieved?  

Is a memory CD8 T cell response needed?  Only CD4 is sufficient?  What is the key population of cells for protection against Shingles and do mRNA vaccines induce them based on what you saw from Covid vaccines?  

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Q9.

What would you want to see in an mRNA based product to want to use it as an alternative to Shingrix? And is there a specific population it could be used in? For example, they show around 90% efficacy in the study of Shingrix, do we know who makes up the 10% and can that be measured in an individual? Like say, "you only produced x amount of antibodies, so you may be in the 10% category" and therefore give them an mRNA shot? Or is it unknown who will get shingles and who won't following the vaccination?

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Q10.

BioNtech (and Pfizer) say this technology is "more scalable" - But is there an issue with supply of Shingrix?
I'm not sure how a more scalable technology, assuming that is true, would be important.

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Q11.

Another important question is, how would you want to see this developed?
With the Covid vaccine, they didn't really dose optimize or find the best dosing interval due to the emergency situation.

How long do you expect a development program to take for a new Shingles vaccine since it's not a worldwide emergency, and what are the specific things you'd want to see to be excited about such a product?

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Q12.

--- What do we know about herpes zoster infection or reactivation following Covid-19 mRNA based vaccinations so far? A lot of publications on this.  Is this a confirmed rare side effect from those vaccines? Or a coincidence? Or still being determined?
And if it is caused by the Covid19 mRNA vaccines, what might be the mechanism behind this, and does this put an mrna-based shingles vaccine in doubt? Or is it specifically the Cov spike antigen causing this problem and therefore won't be an issue here since they will use a VZV antigen?

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