New Haven Register (New Haven, CT)
When time is of the essence
Yale doctor eyes rapid deployment approach to coronavirus vaccine
NEW HAVEN — Big Pharma, incentivized by the federal government, is leading the way in the U.S. on developing a vaccine for COVID-19, but a team at Yale University is working on an approach that could help with the rapid production of a vaccine, which would be needed to inoculate as many people as possible.
Dr. Richard Bucala and his team, based on work it did in 2018 on development of a quickly replicating vaccine for “experimental malaria,” are hoping to apply the platform to COVID-19.
Bucala is the head of rheumatology, allergy and immunology at the Yale
School of Medicine and a professor of medicine, pathology and epidemiology.
The Trump administration has identified five companies or partnerships at the head of the pack in finding a COVID-19 vaccine and is backing them with billions in funding.
They are Moderna in Boston; a combination of
Oxford University and AstraZeneca; Johnson & Johnson; Merck; and Pfizer.
Pfizer and the biotech firm BioNTech on Wednesday released news of a potential vaccine that produced immune responses in healthy patients, according to STAT. Moderna, which was scheduled to start phase 3 of its potential vaccine, has pushed it back phase 3 testing, but is expected to still do it this month.
The New York Times has a vaccine tracker that keeps tabs on advances in the effort. It said there are researchers around the world working on more than 145 vaccines against the coronavirus, with 20
vaccines in human trials.
“The bottom line is that when you have a huge problem you want more than one approach, solution or effort. What we work on is based on technology that was used to develop an effective malarial vaccine in mice,” Bucala said.
The professor said the best way to reduce mortality in a pandemic is a vaccine that can be deployed quickly.
“Among current approaches, vaccine antigen delivered by a self-replicating RNA, or replicon, offers the greatest potential for speed of development, safety and scalable production,” Bucala wrote in a synopsis of his proposal.
RNA is ribonucleic acid, a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions for synthesis of proteins.
All vaccines are based on proteins, Bucala said.
“This RNA is self-replicating, meaning when you inject it into muscle, it produces more copies and more protein antigene,” Bucala said. “The process activates both the antibody and cell based immunity needed for long term protection.”
The professor said there is also a self-replicating RNA effort that is going well at Imperial College in London.
“They have a different platform than ours, but it is the same conceptual and practical advance,” Bucala said. “But all the other vaccine efforts are by traditional approaches or involve RNA or DNA that is going to be challenging to make in time and sufficient doses.”
Bucala said millions of doses of an RNA replicon vaccine can be made from a relatively small amount of production.
“Standard vaccine approaches
that are reliant on the cell-based or eggadaption methods used for seasonal influenza vaccines ... take 17 to 22 weeks from the seed vaccine strain determination until production for shipment.
Thus, the RNA replicon vaccine platform addresses the three key challenges for a pandemic viral vaccine: rapid development, activation of a protective anti-viral immune response, and facile, scalable production,” he wrote.
He said the standard approach is what took place with the H1N1 pandemic flu a decade ago. Bucala said after the viral strain was discovered, it took about 58 months to make the vaccine, and it was not available until after the second pandemic wave had peaked. “Fortunately, that virus did not really affect the United States,” he said.
In his opinion, the coronavirus “is probably here to stay.”
He said there have been
three coronavirus epidemics in the last 15 years, from SARS, (Severe Acute Respiratory Syndrome) in 2003 to MERS (Middle Eastern Respiratory Syndrome) in 2012 and now SARS-CoV-2, responsible for COVID-19.
The doctor said there may not be an outbreak of COVID-19 every year, but maybe every 3 to 5 years.
“So we are going to need to have the capability of producing a lot of vaccine very quickly,” he said. “This is the kind of platform that can do that.”
The researcher said there are a lot of basic questions about coronaviruses that are not known. He said they account for about 20 percent to 30 percent of all common colds. “It is not really known if there is longterm protective immunity,” he said.
He said what they do know so far is that “antibody responses to coronaviruses wane within a few months. So it is just not
known whether infection is protective or if vaccination will be protective.”
“All of that is going to have to be studied and that is why (Dr.) Anthony Fauci says it is a year off. You can’t accelerate the fundamentals of proving a medical intervention works. The clinical trial part of vaccine development, you can’t make it any faster than is the natural process,” he said.
Fauci has been the director of the National Institute of Allergy and Infectious Diseases since 1984 and is the chief government adviser on COVID-19.
Bucala said it is still unknown why children don’t seem to get the disease.
“It is possible that kids, being kids, get lots of cold viruses all the time. Maybe that confers some crossprotection to the coronavirus, but we just don’t know that,” he said. “Others suggest that children don’t have high levels of the host receptor protein responsible for infection.”
The professor said one of the interesting things about coronaviruses is that they have one of the largest RNA genomes of any virus. “Virologists hypothesize that the reason the coronavirus has this huge RNA genome is that it allows it to continually adapt to exist between different species. It has found its ecological niche,” he said.
Bucala said the the replicon-based vaccine his team developed in 2018 for experimental malaria is undergoing pre-clinical validation at Oxford University with planned advancement into human testing.
The professor is part of the governor’s task force interested in coordinating Connecticut’s technology efforts to address the COVID-19 problem. He said he has been pleased with the state’s approach to dealing with the pandemic.