Coronavirus Vaccine Development Barrels Ahead
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Tamlyn Oliver
Posted: March 10, 2020
The development of drugs and vaccines to treat or prevent Covid-19 is well underway fueled by rising infection and death rates. So far, there have been over 116,000 cases of Covid-19 worldwide, with approximately 4,100 deaths reported.
While Trump administration officials have trumpeted a variety of very ambitious timelines for coronavirus vaccines, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, set the record straight recently and made it clear that although development of a vaccine is a clear priority, it will be at least 12 to 18 months before a Covid-19 vaccine is available.
The companies with the most promising candidates are repurposing existing antiviral drugs or leveraging established technology and expertise. Among the vaccine experts expanding their pipelines to include coronavirus is NuGenerex Immuno-Oncology (formerly Antigen Express). The company is applying its CD4+ T-Cell activation platform called li-Key to develop a synthetic peptide vaccine that is modified to stimulate the immune system. According to the company, this type of vaccine is easier and quicker to make compared to traditional alternatives.
In addition to working on a coronavirus vaccine, NuGenerex Immuno-Oncology (NGIO) has several cancer as well as infectious disease vaccines in preclinical or clinical development. Their most advanced compound is currently in Phase II clinical studies in patients with triple negative breast cancer in combination with Merck’s checkpoint inhibitor Keytruda® (pembrolizumab). Previously, this compound was undergoing a large Phase II study in breast cancer patients as well as a Phase I trial in prostate cancer patients.
Eric von Hofe, Ph.D., CSO of NuGenerex Immuno-Oncology, recently spoke to Biocompare about NGIO’s vaccine technology and why he thinks they are well positioned to tackle the coronavirus.
BC: How difficult will it be to develop a vaccine? Is there something unique about the coronavirus, like with HIV, that thwarts vaccine development?
Dr. von Hofe: There is nothing unique about coronavirus that would thwart vaccine development. The problem is the time it takes to produce a vaccine by conventional methods, which can easily be a year or longer.
BC: Can strategies used for the seasonal flu virus also be used against the coronavirus?
Dr. von Hofe: Yes, but the problem is time, coupled with the fact that we really do not know what this virus is going to do. There are recent reports that two strains have been identified in people, indicating that it has mutated at least once. So, particularly for a potentially pandemic virus, time is of the essence. It could wreak havoc by the time a vaccine is available.
BC: You have mentioned the importance of time in coronavirus vaccine development twice already. How does your platform allow for more rapid vaccine development?
Dr. von Hofe: A big advantage of our platform is the speed at which it can respond to a novel viral threat. The initial step is to predict which peptides are the most likely to be effective using computer algorithms, which takes only a few days. Synthesis of peptides is entirely by synthetic means, which is simpler, faster, and more scalable than any process requiring biological systems to produce a vaccine.
BC: How do you determine what peptides to use for your vaccines? What is their mechanism of action?
Dr. von Hofe: After the optimum peptides to be used for the vaccine are identified by computer algorithms, they are subsequently screened against the blood of patients who have recovered from coronavirus. The peptides are modified to ensure interaction with CD4+ T helper cells. These are to the immune system a little like what generals are to the army. They control a lot of its workings, like how the body responds to a new virus. If these cells are specifically activated, they can much better orchestrate an effective response.
BC: What’s the antigen you will use in the vaccine?
Dr. von Hofe: The most likely antigen to target is the so-called spike protein of the coronavirus. This is the portion that it uses to attach to cells and infect them.
Moderna has recently delivered a synthetic RNA vaccine that encodes a portion of the spike protein for clinical testing. So this is a subunit vaccine that is synthetic, which is how they were able to produce it so quickly. The issue here is that Moderna has yet to produce a proven vaccine with this technology.
We are using a synthetic peptide technology to produce a different type of subunit vaccine. The synthetic peptides we use comprise the minimal sequence required to generate an immune response. In contrast, the subunit vaccine being produced by Moderna, an RNA delivered using a lipid formulation to facilitate uptake by cells, is translated into a protein that then generates an immune response. This generates a larger portion of the virus that can have both wanted and unwanted immunological responses, which needs to be assessed in clinical trials. Our vaccine uses much smaller portions of the virus that we know are critical for a very focused immune response directed against critical portions of the virus. Peptides have a long history in the clinic and an excellent safety record. The tradeoff is that our vaccine will not necessarily prevent infection but will lessen the symptoms of people who are exposed to the virus and protect those who are most at risk from the most serious consequences (i.e., death).
BC: What makes you think your strategy will work?
Dr. von Hofe: A number of clinical trials have been conducted with this type of modified peptide vaccine that we are developing. There have been many peer-reviewed publications reporting the results of these studies that demonstrate a robust and long-lived immunological response in people. A 2013 paper covered a Phase I trial of a peptide vaccine in prostate cancer, and a 2016 paper described a Phase II trial of a peptide vaccine in breast cancer.
BC: When do you think you will have a coronavirus vaccine ready for clinical trials?
Dr. von Hofe: We’re aiming for three to five months. As indicated above, the process requires primarily computational and well-established, simple synthetic means for production. The process confirming the activity of peptides using the blood of patients who have recovered from coronavirus also uses straightforward laboratory methods. The real issue is safety, which dictates the level of clinical testing required. Fortunately, as explained previously, a big advantage of using a peptide-based platform is the excellent safety record of peptides in the clinic.
BC: How would you make three billion doses? What manufacturing platform will you use?
Dr. von Hofe: Obviously, it gets difficult to produce billions of doses of a vaccine if some process other than a synthetic one is used. While buildings can be built and enormous flocks of chickens raised, at some point it becomes untenable. For peptide synthesis, we would use 2 mg of vaccine per person, which adds up to 2,000 kg for a billion people. This is still a tall order, but easier than using eggs or cell culture.
BC. What are some regulatory issues for approval of such a vaccine?
Dr. von Hofe: I’m not a regulatory expert so I cannot comment specifically, but the issue has always been that agencies have become comfortable with the traditional process begun around the middle of the last century. Every year there are different strains of flu circulating, but if the same process is used to make the vaccine, regulatory agencies do not require a clinical trial to prove safety and efficacy. However, a new process invariably will raise questions.
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Share
0
Tamlyn Oliver
Posted: March 10, 2020
The development of drugs and vaccines to treat or prevent Covid-19 is well underway fueled by rising infection and death rates. So far, there have been over 116,000 cases of Covid-19 worldwide, with approximately 4,100 deaths reported.
While Trump administration officials have trumpeted a variety of very ambitious timelines for coronavirus vaccines, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, set the record straight recently and made it clear that although development of a vaccine is a clear priority, it will be at least 12 to 18 months before a Covid-19 vaccine is available.
The companies with the most promising candidates are repurposing existing antiviral drugs or leveraging established technology and expertise. Among the vaccine experts expanding their pipelines to include coronavirus is NuGenerex Immuno-Oncology (formerly Antigen Express). The company is applying its CD4+ T-Cell activation platform called li-Key to develop a synthetic peptide vaccine that is modified to stimulate the immune system. According to the company, this type of vaccine is easier and quicker to make compared to traditional alternatives.
In addition to working on a coronavirus vaccine, NuGenerex Immuno-Oncology (NGIO) has several cancer as well as infectious disease vaccines in preclinical or clinical development. Their most advanced compound is currently in Phase II clinical studies in patients with triple negative breast cancer in combination with Merck’s checkpoint inhibitor Keytruda® (pembrolizumab). Previously, this compound was undergoing a large Phase II study in breast cancer patients as well as a Phase I trial in prostate cancer patients.
Eric von Hofe, Ph.D., CSO of NuGenerex Immuno-Oncology, recently spoke to Biocompare about NGIO’s vaccine technology and why he thinks they are well positioned to tackle the coronavirus.
BC: How difficult will it be to develop a vaccine? Is there something unique about the coronavirus, like with HIV, that thwarts vaccine development?
Dr. von Hofe: There is nothing unique about coronavirus that would thwart vaccine development. The problem is the time it takes to produce a vaccine by conventional methods, which can easily be a year or longer.
BC: Can strategies used for the seasonal flu virus also be used against the coronavirus?
Dr. von Hofe: Yes, but the problem is time, coupled with the fact that we really do not know what this virus is going to do. There are recent reports that two strains have been identified in people, indicating that it has mutated at least once. So, particularly for a potentially pandemic virus, time is of the essence. It could wreak havoc by the time a vaccine is available.
BC: You have mentioned the importance of time in coronavirus vaccine development twice already. How does your platform allow for more rapid vaccine development?
Dr. von Hofe: A big advantage of our platform is the speed at which it can respond to a novel viral threat. The initial step is to predict which peptides are the most likely to be effective using computer algorithms, which takes only a few days. Synthesis of peptides is entirely by synthetic means, which is simpler, faster, and more scalable than any process requiring biological systems to produce a vaccine.
BC: How do you determine what peptides to use for your vaccines? What is their mechanism of action?
Dr. von Hofe: After the optimum peptides to be used for the vaccine are identified by computer algorithms, they are subsequently screened against the blood of patients who have recovered from coronavirus. The peptides are modified to ensure interaction with CD4+ T helper cells. These are to the immune system a little like what generals are to the army. They control a lot of its workings, like how the body responds to a new virus. If these cells are specifically activated, they can much better orchestrate an effective response.
BC: What’s the antigen you will use in the vaccine?
Dr. von Hofe: The most likely antigen to target is the so-called spike protein of the coronavirus. This is the portion that it uses to attach to cells and infect them.
Moderna has recently delivered a synthetic RNA vaccine that encodes a portion of the spike protein for clinical testing. So this is a subunit vaccine that is synthetic, which is how they were able to produce it so quickly. The issue here is that Moderna has yet to produce a proven vaccine with this technology.
We are using a synthetic peptide technology to produce a different type of subunit vaccine. The synthetic peptides we use comprise the minimal sequence required to generate an immune response. In contrast, the subunit vaccine being produced by Moderna, an RNA delivered using a lipid formulation to facilitate uptake by cells, is translated into a protein that then generates an immune response. This generates a larger portion of the virus that can have both wanted and unwanted immunological responses, which needs to be assessed in clinical trials. Our vaccine uses much smaller portions of the virus that we know are critical for a very focused immune response directed against critical portions of the virus. Peptides have a long history in the clinic and an excellent safety record. The tradeoff is that our vaccine will not necessarily prevent infection but will lessen the symptoms of people who are exposed to the virus and protect those who are most at risk from the most serious consequences (i.e., death).
BC: What makes you think your strategy will work?
Dr. von Hofe: A number of clinical trials have been conducted with this type of modified peptide vaccine that we are developing. There have been many peer-reviewed publications reporting the results of these studies that demonstrate a robust and long-lived immunological response in people. A 2013 paper covered a Phase I trial of a peptide vaccine in prostate cancer, and a 2016 paper described a Phase II trial of a peptide vaccine in breast cancer.
BC: When do you think you will have a coronavirus vaccine ready for clinical trials?
Dr. von Hofe: We’re aiming for three to five months. As indicated above, the process requires primarily computational and well-established, simple synthetic means for production. The process confirming the activity of peptides using the blood of patients who have recovered from coronavirus also uses straightforward laboratory methods. The real issue is safety, which dictates the level of clinical testing required. Fortunately, as explained previously, a big advantage of using a peptide-based platform is the excellent safety record of peptides in the clinic.
BC: How would you make three billion doses? What manufacturing platform will you use?
Dr. von Hofe: Obviously, it gets difficult to produce billions of doses of a vaccine if some process other than a synthetic one is used. While buildings can be built and enormous flocks of chickens raised, at some point it becomes untenable. For peptide synthesis, we would use 2 mg of vaccine per person, which adds up to 2,000 kg for a billion people. This is still a tall order, but easier than using eggs or cell culture.
BC. What are some regulatory issues for approval of such a vaccine?
Dr. von Hofe: I’m not a regulatory expert so I cannot comment specifically, but the issue has always been that agencies have become comfortable with the traditional process begun around the middle of the last century. Every year there are different strains of flu circulating, but if the same process is used to make the vaccine, regulatory agencies do not require a clinical trial to prove safety and efficacy. However, a new process invariably will raise questions.
FEATURED PRODUCTS
The CellASIC® ONIX2 Microfluidic SystemThe CellASIC® ONIX2 Microfluidic System
For advanced live cell imaging and microscopy. The ability to grow, observe and manipulate complex cultures requires precision control over the cell ... Learn More
Modular Incubator ChamberModular Incubator Chamber
The Modular Incubator Chamber (MIC-101) provides a simple, low-cost way to create the right environment for your cell culture and experiments. Whether... Learn More
ProQuantum High-Sensitivity ImmunoassaysProQuantum High-Sensitivity Immunoassays
Invitrogen™ ProQuantum™ high-sensitivity immunoassays are a new line of ready-to-use kits that provide an easy method of measuring protein analytes ... Learn More
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