By WP Creative Group
Every February, the World Health Organization convenes top epidemiologists to make a critical decision for the Northern Hemisphere by answering the question: What are this year’s most threatening flu strains? By October, purpose-built vaccines are rolling out of production and into arms across the continent, saving tens of thousands of lives annually.
This decision about which strains to target is based on rich, reliable data. But it’s still a bit of a gamble. By fall, some strains could look almost unrecognizable, according to Gregory Glenn, president for research and development at Novavax and an expert with nearly three decades in vaccine design, development and delivery. The annual flu vaccine will still be immunogenic against some of them. Against others, it won’t.
This is the challenge Glenn is focused on solving at biotech company Novavax, where he heads R&D. Glenn and his team are working on vaccines for a number of diseases including, for the past two years, covid-19.
Cutting-edge innovation is helping vaccine makers put the pieces in place to help protect against these diseases — and whatever may crop up next. But for all the world-changing new technology a team like Glenn’s has at its disposal, decades-deep, human-tested vaccine science is the foundation of their work.
“The original observations were this: If someone got smallpox, for example, and lived, they were immune for life,” Glenn said. “That was pretty clear. Then, the scientists who pioneered the smallpox vaccination observed that milkmaids who got cowpox, which is closely related, never got smallpox. The observation that infection led to protection for this particular virus was solid for many decades.”
Viruses like smallpox are dangerous, so over time vaccine developers found ways to mimic their effects on the body to generate just the right reaction from the immune system without introducing the real virus. That’s a world apart from anecdotes about milkmaids, but the principle is still there. “Give somebody something that tells the body it’s been infected, engage the immune system in a specific way, and you’ll get protection,” Glenn said.
In the age of genetics and molecular science, researchers have added new tools to that equation. But scientists still have to answer the same fundamental question: Why does infection happen?
Finding the origin of infection requires looking carefully at very small things.
Every snowflake is unique, wildly intricate, and prone to vanishing in an instant. This is not dissimilar to a virus protein in the lab. As quickly as a snowflake dissolves, evanescent virus proteins can become distorted and lose their original form, making it tough to create an imitation accurate enough for the body to recognize, fight and develop immunity against.
To solve this, Glenn’s team developed what he calls “a very special handoff” of the fragile viral protein to teach the human immune system to recognize it. “We make the protein in an insect cell, so it’s sitting happily on the surface membrane of an insect cell and then we are able to extract it away,” Glenn explained. “We transfer it to the surface membrane of a soap bubble, basically, and so now it’s preserved, like it would be in nature but it’s in a nanoparticle.” The aim, he said, is that this nanoparticle is one that the human immune system can be programmed to recognize and react to in a way that induces immunity.
In other words, this microscopic vessel bearing a virus protein knock-off — also referred to as a recombinant, insect cell-derived nanoparticle — is designed to fool the human body into thinking it is the actual virus, triggering an immune response.
It may sound futuristic, but the protein subunit vaccine that delivers it has been used millions of times. It’s been employed for four decades in vaccines for diseases like hepatitis B, shingles, and haemophilus influenzae type B (Hib), the latter of which was the leading cause of meningitis and pneumonia in young children across the U.S. before routine vaccination started in the 1980s.
During the 2014 Ebola epidemic, the Novavax team observed the difficulty in safely distributing vaccines to far-flung parts of the world. The more stable a vaccine, the greater possibility it could be dispersed — over whatever great distances, in whatever extreme climates — without being compromised. Around this time, the team realized that subunit vaccines, which could be stored using standard, refrigeration technology, could be the answer.
But because of the way the immune system recognizes the intruding protein, some past subunit vaccines have shown relatively weaker immunogenicity. Rather than abandon the approach, the team decided to look at another existing technology that could help them solve that challenge.
“When you look at a virus or bacteria, you see a lot of ‘dirty’ stuff — the components on the surface,” Glenn said. “The immune system is programmed to spot those things. If you have a recombinant protein — you need a secondary element to rev things up. That’s where an adjuvant comes in.”
Adjuvants — naturally derived substances that spark the immune system and help spur the creation of antibodies — have been in use to enhance immunogenicity in vaccines for nearly a century. Novavax’s adjuvant of choice comes from saponins — compounds found in plants like beans and green peas. Novavax’s adjuvant specifically is derived from the bark of the Chilean soapbark tree. Combining this adjuvant with the nanoparticle may yield a bigger, better immune response.
Glenn’s lab has been compiling encouraging data on the contribution of the adjuvant since the team began testing Novavax’s Ebola vaccine in a clinical trial in 2015.
“The data was so informative,” Glenn said. “We were able to see the great delta in the functional immunity between ‘no adjuvant’ and ‘adjuvant.’ That was a big inflection point, and it was all brought about by Ebola.” Seeing the data, they began applying this concept to other viruses, and when covid-19 surfaced, Glenn said, the concept was poised and ready. Now, Glenn and team are looking ahead at how to iterate from here.
“I think most people are of the same opinion that, eventually, the virus that causes covid-19 is going to get into this march of a seasonal winter virus like flu — a very serious respiratory virus which we’ll need a vaccine for each year,” he said. Future vaccines could leverage this technology platform to make it a reality.
Studies show that the probability of a pandemic with similar impact to covid-19 is about one in 50 in any given year. That probability is only growing, experts say, highlighting the necessity to have vaccine technology ready to iterate, along with manufacturing and distribution infrastructure at the ready.
Novavax Chief Business Officer John Trizzino said vaccine approaches that rely on established learnings and new iteration are Novavax’s approach when it comes to addressing fast-moving epidemics now and in the future.
With the arrival of covid-19, critical transformations in the way vaccines are approved, manufactured and distributed are underway: more efficient regulatory processes, streamlined supply chain logistics, better global infrastructure for getting the shot where it’s needed most and important global private-public partnerships to support that infrastructure.
Thanks to these incremental innovations, Trizzino said, “what once would have taken 10 or more years might now take about 24 months.” Meanwhile, companies like Novavax are constantly surveilling the landscape to anticipate the next potential threat.
“As soon as we pick up the signal of a potential outbreak, the Discovery team starts to look for more information and as appropriate, secures the genes to plug it into our platform,” Trizzino said. “Covid-19 taught us so much. We are prepared and already taking steps now to be prepared for the next emerging infectious disease.”
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