Developing vaccines no easy task


By Gary Budzak - gbudzak@aimmediamidwest.com



Ambegaokar

Ambegaokar


Concerns about developing a vaccine for COVID-19 were addressed by an Ohio Wesleyan University professor on June 24.

“When Will It Be Safe To Go Out Again? Challenges in Vaccine Development, and Why It May Be OK Without One” was the topic of an hour-long lecture by Ohio Wesleyan’s Director of Neuroscience Suren Ambegaokar.

The short answer, he said, is “we don’t know. So I apologize if the title is a bit misleading, but I wanted to provoke. I think we’ve taken for granted how hard it is to actually make a vaccine. I wanted to re-set your expectations.”

Ambegaokar, a virologist (one who studies viruses), discussed the steps involved in making a vaccine that is safe and effective, as well as testing and practical limitations.

If an unvaccinated person is initially infected by a bad virus, he said, they may be ill for an average of three days to three weeks before possibly recovering. With COVID-19, though, Ambegaokar said there can be permanent damage to organs.

If one is vaccinated, however, infection is still possible, but there would either be no symptoms or they may have mild symptoms for an average of up to three days. They also protect others from getting infected, he said.

“No vaccine is 100% effective, it reduces the odds of you being infected,” Ambegaokar said. “Also, some people are unable to be vaccinated due to certain conditions such as immune suppression. Maintaining immunity in those around these people protects them from disease.”

The first barrier in vaccine-making is getting it to testable. Ambegaokar said the traditional method of making a vaccine is in three steps: Isolating the pathogen from a patient or environment, growing a lot of the virus in a dish so it can be altered, and making the virus non-dangerous (by either killing it, having it mutate, or using part of it) which then needs to be tested in animals and humans.

Each one those steps can take months or years, he said.

Another bottleneck is pre-clinical tests with animals before it gets to humans. In these trials, a vaccine’s safety and efficacy are measured. Safety concerns are toxicity, side effects and dosage amount. For efficacy, is it immunogenic (does it work), and are the antibodies that are being made effective at neutralizing the virus?

There needs to be a balance between safety and efficacy, and that process can easily take five years, Ambegaokar said.

A third problem is in the clinical trials, where the vaccine is tested on humans. There are three phases in the trials. In phase one, 10 to 100 healthy persons are tested, mainly to see if the vaccine is toxic and at what doses. In phase two, hundreds or real patients are tested to see if the vaccine is as effective as expected. In the third phase, thousands to tens of thousands of patients are tested to see if the vaccine is still safe, what are the side effects, and is it still effective.

“Altogether, less than 10% of therapeutic candidates are approved for general use,” Ambegaokar said.

Typically, successful clinical trials take one to three years, and then the results are sent to the Federal Drug Administration for review and approval. That takes another six months to a year.

Lastly, if a vaccine candidate does meet FDA approval, it must be mass-produced by the millions or billions of doses in specialized facilities and packaged in individual, sterile vials. That can take up to five years, he said.

Starting now from scratch, adding up all the processes, and assuming all goes smoothly, a vaccine could be ready in 2036, Ambegaokar said.

Despite this sobering prognosis, we have been hearing that a vaccine could be ready by year’s end or in the next year. Why is that?

There are new ideas being tested for SARS-CoV-2 and COVID-19 to speed up the process, Ambegaokar said. In 2002, the SARS-CoV-1 struck, and what is known about that similar infectious disease can be applied to vaccines for the current pandemic. That means possible vaccines can go straight to clinical trials. If any pass, they can go to the FDA with priority.

Ambegaokar said that could mean a vaccine would be ready in the fall of 2028. “We’re risking safety to speed it up,” he said.

So how do we shave the other seven years off?

There are genetic vaccines (engineered using DNA, RNA and viral vectors whose blueprint would be embedded) that would be quicker to produce than a traditional vaccine. The problem is, we have no idea if this will actually work, he said.

Another idea is to go ahead and build vaccine factories and begin mass-producing now before clinical trials are finished. This could cost billions, though, a huge risk for companies. However, the Gates Foundation has committed to covering the costs to biopharma companies for up to seven candidate vaccines.

“There’s still no guaranteeing these will work,” he said. “I hope you can appreciate how many things have to go right for this to happen. Is it possible? Yes. Is it probable? I would say it’s not. The odds would be against it, but it would great if it did.”

Another idea is the “human challenge studies” where scientists intentionally infect healthy people with the coronavirus to test vaccines.

“This has not been approved yet, but it’s a very interesting idea,” Ambegaokar said. “But it’s a very different way of testing.”

Finally, he said our options are limited, but we can manage the contagion without having a vaccine available. This means the virus is not eradicated, but we can have interactions relatively safely.

First, he said there needs to be massive community testing with in-depth contact tracing, especially those not showing symptoms.

“We need to have a door-to-door campaign, as many people as possible, baseline testing to find out how much virus is in our communities,” Ambegaokar said. “Every single health official will agree that this has to be essential to plan to control the spread of the virus.”

Testing works to curb the spread, he said. He pointed to China, Singapore and South Korea. “Again, not eradicated, new cases are still likely to appear for the foreseeable future, but hopefully at a substantially reduced rate.”

“By all measurements, the U.S. is the worst country in handling this pandemic,” Ambegaokar said. As of June 24, “There is no national strategy for massive testing. The government has failed in their responsibility to do this. It’s just baffling to me why we aren’t doing this more. We can make the tests, do them quickly.”

He said the states are doing half a million tests a week. However, the Rockefeller Foundation is attempting to increase testing nationwide to 30 million per week by the end of summer.

The second option is antiviral therapeutics. If a vaccine is the defense, the antiviral is the offense. It’s the viral equivalent of an antibiotic for a bacterial infection. He said antivirals are currently being used to control HIV.

The antiviral attacks the virus and is easier to make than a vaccine. It can reduce the length or severity of COVID, or one’s ability to shed the virus. A particularly good antiviral could be taken like a “daily vaccine” to decrease the risk of becoming infected if exposed to the virus.

Ambegaokar said there are several already-approved existing drugs for other diseases that are being tested for COVID-19.

In the meantime, he said the bare minimum safety measures the public can do is to maintain physical distancing and wear masks in public areas.

“At our current state, SARS-CoV-2 will likely become endemic (prevalent) to the U.S. — we should develop strong public policies with this in mind, rather than uncoordinated and underfunded efforts,” he concluded.

In response to a viewer question, Ambegaokar said herd immunity would take years to achieve, but a vaccine can help in getting to that level. He said that if a vaccine is developed, frontline health care workers would receive the first doses in the first year before anyone else.

Ambegaokar’s talk was part of the free online course called “We’re in This Together: An Interdisciplinary Exploration of the Coronavirus Pandemic.” Taught by 24 OWU faculty members, the course is open to students and the public alike. OWU spokespersons have said more 1,200 people are participating in the class, and more than 380 people are taking part in a Facebook COVID-19 Class Discussion Group.

For more information about OWU’s “We’re in This Together” course, visit www.owu.edu/COVIDclass.

Ambegaokar
https://www.delgazette.com/wp-content/uploads/sites/40/2020/06/web1_Amegaokar.jpgAmbegaokar

By Gary Budzak

gbudzak@aimmediamidwest.com

Gary Budzak may be reached at 740-413-0906 or on Twitter @GaryBudzak.

Gary Budzak may be reached at 740-413-0906 or on Twitter @GaryBudzak.