Covid Vaccines 2.0

This NYT article on the next generation of Covid vaccines was the most interesting article I’ve read on vaccines in a while.  Fascinating stuff– and very encouraging:

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic. The vaccine, called NDV-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

I remember reading years and years ago about how we were using this old technology– eggs!!– to make vaccines and we were looking to move past that.  And we clearly have.  But, little did I realize that there are huge advantages to this easy to use, low-cost technology when you want to vaccinate the world.

If NDV-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NDV-HXP-S for themselves or acquire it at low cost from neighbors.

“That’s staggering — it would be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.

First, however, clinical trials must establish that NDV-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.

“It’s a home run for protection,” said Dr. Bruce Innis of the PATH Center for Vaccine Innovation and Access, which has coordinated the development of NDV-HXP-S. “I think it’s a world-class vaccine.” …

“It made sense to try to have a better vaccine,” said Dr. McLellan, who is now an associate professor at the University of Texas at Austin.

In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.

The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

Dr. McLellan also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

Meanwhile, Dr. Innis and his colleagues at PATH were looking for a way to increase the production of Covid-19 vaccines. They wanted a vaccine that less wealthy nations could make on their own…

The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.

The PATH team wondered if scientists could make a Covid-19 vaccine that could be grown cheaply in chicken eggs. That way, the same factories that make flu shots could make Covid-19 shots as well.

In New York, a team of scientists at the Icahn School of Medicine at Mount Sinai knew how to make just such a vaccine, using a bird virus called Newcastle disease virus that is harmless in humans.

For years, scientists had been experimenting with Newcastle disease virus to create vaccines for a range of diseases. To develop an Ebola vaccine, for example, researchers added an Ebola gene to the Newcastle disease virus’s own set of genes.

The scientists then inserted the engineered virus into chicken eggs. Because it is a bird virus, it multiplied quickly in the eggs. The researchers ended up with Newcastle disease viruses coated with Ebola proteins.

At Mount Sinai, the researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When they learned about Dr. McLellan’s new HexaPro version, they added that to the Newcastle disease viruses. The viruses bristled with spike proteins, many of which had the desired prefusion shape. In a nod to both the Newcastle disease virus and the HexaPro spike, they called it NDV-HXP-S.

PATH arranged for thousands of doses of NDV-HXP-S to be produced in a Vietnamese factory that normally makes influenza vaccines in chicken eggs. In October, the factory sent the vaccines to New York to be tested. The Mount Sinai researchers found that NDV-HXP-S conferred powerful protection in mice and hamsters.

“I can honestly say I can protect every hamster, every mouse in the world against SARS-CoV-2,” Dr. Peter Palese, the leader of the research, said. “But the jury’s still out about what it does in humans.”

The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.

“We are very excited about this, because we think it’s a way of making a cheap vaccine,” Dr. Palese said.

One of the reasons I remain very optimistic about our long-term fight against Covid-19 is that scientists are continuing to do amazing work on this.  Of course, there may be some rough bumps in the road and tough times, but progress like this NDV-HXP-S vaccine really do mean we almost surely will never be at the  mercy of Covid-19 again like we were in 2020.

 

About Steve Greene
Professor of Political Science at NC State http://faculty.chass.ncsu.edu/shgreene

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