When NPR first featured the work of Brazilian scientists and longtime best friends Patricia Neves and Ana Paula Ano Bom, they were in the early stages of an audacious attempt to break open global access to vaccines – specifically the ones made with the cutting-edge mRNA technology that Moderna and Pfizer developed for use against COVID.

Neves and Ano Bom had been dismayed at Moderna and Pfizer’s unwillingness to share their know-how during the pandemic, leaving people in low- and middle-income countries like Brazil waiting to get the life-saving vaccines for months after they’d been made widely available in wealthy countries.

The Brazilian friends’ solution: invent their own version of an mRNA vaccine against COVID, then offer up the patent and the manufacturing process to vaccine makers around the world, essentially for free.

And they planned to target plenty of other viruses beyond COVID. These vaccines work by inserting a recipe into the body — the mRNA strand — that teaches cells to build a piece of the targeted virus that the body’s immune system gears up to attack. That way when a person is infected with the actual virus, the body is ready for it. 

So Neves and Ano Bom’s vision was to essentially build their mRNA COVID vaccine as a plug-and-play system that could be quickly adapted to carry mRNA strands against all sorts of other disease threats as they emerged around the world.

Neves, an immunologist, originally conceived of the idea because before the pandemic she’d been working with mRNA as part of a project to create a vaccine-like treatment for breast cancer. When the news came out that Moderna and Pfizer’s mRNA efforts against COVID were showing promise, Neves thought, why not switch gears to see if her type of mRNA could also work in a COVID vaccine?

She knew a major difficulty would be figuring out how to devise a tiny fat particle to encase the mRNA so that it remains intact once inserted into the body. But, as it happened, Neves had an ideal partner for that challenge in her pal Ano Bom.

Ano Bom is a biochemist who works at the same institution as Neves — the Bio-Manguinhos Fiocruz Foundation, which is Brazil’s premier public agency for vaccine research and development. And Ano Bom had already gained expertise working on an encapsulation process for the breast cancer effort. But perhaps most important, the two women — who have been close since they attended college together two decades ago — share an unusual zest for going after goals even scientists at their own institution initially considered unrealistic.

"Yeah," said Ano Bom at the time, "We are innovative and — I don't know — maybe crazy."

That was two years ago. We caught up with the duo on a zoom call to check on their progress … and found them in ebullient spirits.

“Oh, we’re at a whole other level!” says Ano Bom. Their team has now completed creation of a COVID vaccine candidate using both an mRNA component and an encapsulation method that is entirely their own invention.

This stands in contrast to a related but separate effort by a team in South Africa to essentially replicate Moderna’s COVID vaccine recipe through reverse engineering. While both projects have received support from the World Health Organization and the scientists involved have conferred, “our strategy was to escape as much as possible the [existing] patents,” notes Neves. “We designed our elements [to be] different from the ones that Moderna and Pfizer are using.”

What’s more, she says, in mouse studies the Brazil team’s vaccine has been shown “100% effective” against COVID. The team has also cleared another hurdle: setting up a manufacturing facility in Brazil that meets the rigorous safety standards needed to produce vaccine doses at the scale required for the next phase of development. It’s the first facility of its kind in Latin America, says Neves.

Next month the team will begin a final round of safety studies in animals. If all goes well, by the middle of next year they’ll launch clinical trials in people.

Meanwhile, Brazil’s Ministry of Health has expanded the team’s mission — and funding — to create mRNA vaccines against multiple other diseases.

“We are starting to work with health emergencies,” says Neves. “Every day we have a different plague to deal with.”

These pathogens include leishmaniasis, Oropouche, mpox and RSV — and their candidate mRNA vaccine against RSV is already in animal studies. They’re also researching ways to use the technology in various therapies.

“We started as four people and a dream,” says Neves, referring to herself, Ano Bom, as well a colleague who contributed early work and Sotiris Missailidis, the then-head of research and development at their agency. Missailidis, notes Neves, “was the person who believed in us since the beginning,” scraping together a few tens of thousands of dollars for the team to launch back when higher ups were dismissing their proposal.

“Now,” marvels Neves, “this is one of the most important projects in [our institution].”

Ano Bom nods in agreement, “I think our mission is almost completed,” she says. “It’s such a proud feeling.”

Their work has also gained increasing international recognition. The women note that NPR’s original story — which observed that unlike big pharmaceutical companies, Neves and Ano Bom are not working for profit — prompted the Argentina-based Ibero American Society of Neonatology (SIBEN) to honor them with a specially created “Altruism Award for the Improvement of World Health.”

Says Ano Bom of the ceremony, “It was a very emotional moment.”

Unexpected hurdles

But the two also stress that the science that has led to all this has not been easy.

“Oh my God!” says Neves as both she and Ano Bom erupt in laughter, “It’s been hard work. A lot, a lot of hard work!”

This has included creative pivoting to overcome multiple setbacks. For instance, the team had originally hoped to use the same type of mRNA that Neves had been developing for the breast cancer project. It’s called “self-amplifying” because the mRNA contains messages that instruct a person’s body to make more of it. You just insert a small amount of the mRNA in the body and the body takes care of manufacturing the rest. This requires less raw material, lowering the cost of producing the vaccine — an especially valuable feature for lower income countries.

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Unfortunately, the mouse studies of their version of the vaccine using this self-amplifying mRNA turned up disappointing results. “We were finding medium protection,” says Neves. “Between 40 and 60% effective.”

The good news was that the team had simultaneously been developing conventional mRNA strands against COVID because as Neves puts it, “we wanted to understand the whole technology.” And this was the version that did prove enormously successful against COVID.

Long term, Neves says, she hasn’t given up on developing vaccines using self-amplifying mRNA. “We think it will be the next generation,” she says. “But we realized we would need to invest more time [to make it work]. And our wish was to have a vaccine as soon as possible, no matter what.”

Cheerful cursing

Once they’d settled on the mRNA formulation, says Neves, “we started a race to find a lipid” — meaning the fat particle that would encase the mRNA. It could not involve components or processes already under patent, “so we’d have freedom to operate,” and it had to be at an affordable price. “So a lot of different things that are difficult to have.”

Here again, the team hit a snag when a class of lipids that they thought would be fairly easy to work with proved complicated. “I think that was one of the most apprehensive moments,” says Ano Bom.

Ultimately they turned to a different subset of lipids, with the lab technicians working increasingly late hours to make up for the lost time. Neves recalls how one night at around 11 p.m. the lab team sent the two of them a video of their progress. Of course she opened the file right away, adds Neves. “I’m always online — 24-7!”

On the video, the team read out the results coming off a computer, each data point confirming that this particular lipid formulation was going to work. Then, says Ano Bom, the technicians broke into cheers.

“They were shouting, ‘Conseguimos!’ ” — Portuguese for, “We did it!” And also, Ano Bom adds with a chuckle, “some curse words.”

For Neves the overriding reaction was “the sensation of relief.”

“We are so committed to this mission,” she says. “So each step that we were able to prove that we are capable of doing this was a big relief.”

And for all the boldness of their original vision, the two seem a bit stunned to find themselves on the cusp of actually fulfilling it.

“I personally never imagined we would achieve what we achieved,” says Neves. “I still don’t believe it.”

They’re ‘the candy and the wrapper’

Ano Bom adds that she considers their friendship to be a part of that accomplishment.

“In the beginning of this journey, we told each other we will never fight over the work.” Not only have they kept that vow, she says, they’ve grown closer — taking turns being the one who gets discouraged and the one who bucks the other up.

“I think our friendship, it will be forever,” Ano Bom says, adding with a laugh: “We’re casca de bala!” — a Portuguese expression that literally translates as the candy and the wrapper.

Neves joins in with a broad grin. “I think this is the secret of the success of this project!”

Then her expression grows thoughtful as she explains that she’s serious. “It’s very, very difficult to have the responsibility of doing something so big alone,” she says. “I think that we succeed because we are in it together.”

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