An NCI-designated Comprehensive Cancer Center
By Letisia Marquez | March 24, 2020
Don Diamond - Tim Nesvig Lymphoma Fellowship Don Diamond, Ph.D.
As an institution dedicated to fighting cancer, diabetes and other life-threatening diseases, City of Hope is addressing the novel coronavirus threat on a number of fronts, including the preclinical development of a coronavirus vaccine.
 
“Given the urgency of this pandemic, City of Hope is employing its vast expertise using the immune system to fight viral infections,” said Don Diamond, Ph.D., viral immunologist with City of Hope’s Department of Hematology. “In particular, City of Hope hematologists successfully treat a great number of infections that bone marrow/stem cell transplant recipients and other immune-compromised cancer patients can become exposed to during their treatment. So City of Hope has both the expertise in researching and treating some of the worst viral infections out there.”
 
City of Hope developed the Triplex vaccine  against cytomegalovirus (CMV), a type of herpes virus, that  similar to the coronavirus  can cause pneumonia and other serious complications in patients with weakened immune systems. In a phase 2 randomized clinical trial, Triplex prevented CMV from duplicating out of control in bone marrow and stem cell transplant patients, and they were 50% less likely to develop health complications related to the virus than patients who did not take Triplex.
 
Using that data and other immunological research, Diamond’s goal is to develop a COVID-19 vaccine using a unique platform. Diamond and his team plan to work with the Food and Drug Administration (FDA) to develop a path to potentially begin phase 1 clinical trials in six to eight months.
 
Here, Diamond addresses how a vaccine is developed, how it works and what makes the development of a coronavirus vaccine unique.

How is a vaccine developed?

You first need the sequence of the virus. Because COVID-19 is related to other viruses of the same type, we have a real large reservoir of information that can lead us to predict what antigens, or proteins from the virus, would be the most immunogenic. We are drawing upon previous information that allows us to understand what humans make immune responses to if they are infected with the actual pathogen, or virus. So we can do this by sort of a reverse genetic engineering of the virus, isolating various pieces and studying in culture whether human serum or T cells can eventually recognize parts of the virus. Once you've identified what are the most antigenic, immunogenic parts of the virus, you insert them into a carrier. It can be a benign virus carrier, so a virus that is not harmful. Or you can use a nonliving carrier, or an artificial carrier such as a nanocarrier. All of those are being researched right now at City of Hope and other institutions.
 

Once the vaccine is developed, how does it work?

The best vaccines work to mimic the pathogen without causing harm. The vaccine should generate antigens that hopefully prime the immune system to make antibodies and T cell responses. Now, what you also need out of a vaccine is something called durability. That’s the most crucial thing because what you're counting on in a protective vaccine is that, well, I can't be vaccinated every day of the week, right? So the immunity is going to have to last for awhile. So that's really the key element of a successful vaccine. So the pathogen, in most, but not all, circumstances, gives you lifetime immunity. For instance the measles, mumps, rubella (MMR) vaccine gives you lifetime immunity to these diseases. As a child, you receive the MMR vaccine to do that. So the same principle applies here.
 

Are you trying to develop durability with a coronavirus vaccine, or would it be like the flu vaccine that you have to get every year?

Durability would be ideal but the challenge is no one knows what kind of durability past coronavirus vaccines have had. With SARS and MERS, also coronaviruses, they did make vaccines but the fact is that the outbreaks petered out. And so you couldn't do a traditional placebo-controlled trial to determine if the vaccine was actually working or not. So nobody knows, and nobody knows whether the vaccines that are currently being investigated will have any efficacy short term or long term until you actually test them in patients.

Are there particular challenges that you need to take into account as you develop a COVID-19 vaccine?

COVID-19 infects lung cells and does tremendous damage to them. Part of that damage is caused by the immune system attacking the virus in the lungs, thereby causing tremendous inflammation of the lungs. A protective vaccine would spur an immune response to be mounted before the virus replicates to huge numbers and causes physiologic damage.
 
Another challenge is that coronaviruses are also single-stranded RNA viruses, so the potential for mutation is quite high. COVID-19 is about 75% identical to SARS and about 50% identical to MERS. So it is unlikely that vaccines made for those viruses would have much value for this one. We do have some information to begin with, but are doing more research.

What is the FDA process to get a vaccine approved for use in patients?

What we plan to do is start a simultaneous animal safety study and petition the FDA to allow us to do a phase 1 safety study in humans. Following successful completion of a phase 1 study, an efficacy study such as a phase 2 trial can begin. People who are at risk of acquiring the infection would be given either the vaccine or the placebo in a double-blinded fashion. If the vaccine is successful, there will be greater protection in the group that got the vaccine. This is what we did with our CMV vaccine trial, and we are confident we can do this again.

What can you tell us about the City of Hope vaccine you’re developing?

We're working very hard to produce different candidates and will study them in various conditions to answer the questions that are unknown. We are not using the actual pathogen. We’re using a carrier and made synthetic versions of the antigens, and we're inserting that into a carrier, what’s known as a subunit strategy. City of Hope will initially develop the vaccine, but at some point we hope to have a commercial partner.

Lastly, as a viral immunologist, what advice do you have for the general public about staying healthy?

People need to follow recommendations being made by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, particularly social distancing. What California has done so far — ordering its 40 million residents to stay home should help keep COVID-19 from spreading if everyone adheres to social distancing and other recommendations that are being made.

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