Novavax’s long-awaited COVID-19 vaccine authorizations offer an alternative to mRNA | Science

The small Maryland biotechnology company Novavax has finally joined the ranks of high-profile COVID-19 vaccine developers after winning emergency authorizations in recent days for its candidate. The decisions by the World Health Organization (WHO) and the European Commission make the company’s product the first protein-based vaccine green-lighted by those bodies and opens it to broad distribution to some of the poorest countries.

With less stringent temperature requirements and a refrigerator life 8 months longer than messenger RNA (mRNA) vaccines for COVID-19, Novavax’s product promises to buttress global vaccine supply as the Omicron variant spreads rapidly. It may also offer an alternative for consumers wary of currently available vaccines that deliver genes directing cells to make the virus’ spike protein. The Novavax vaccine instead delivers the spike protein itself.

The vaccine, which is now being manufactured under a license by the Serum Institute of India, received a WHO emergency use listing on 17 December. That was required for distribution by the COVID-19 Vaccines Global Access (COVAX) Facility, the global facility supplying COVID-19 vaccines to countries in need.

And the Commission granted its authorization on Monday following a positive recommendation from the European Medicines Agency. The decision makes it the fifth COVID-19 vaccine allowed in the European Union’s 27 member countries. The Commission in August prepurchased up to 200 million doses of the Novavax jab, which are expected to start arriving in January 2022.

“The mRNA vaccine platform has been very important so far, but we need more vaccines in the mix,” says Luciana Borio, a senior fellow for global health at the Council on Foreign Relations. WHO’s green light will allow Novavax, with Serum, to begin to deliver a promised 1.1 billion vaccine doses to COVAX, she notes.

As for Novavax’s European authorization, “It’s huge to get validation from a regulatory body that’s not in Asia,” says Mayank Mamtani, a biotechnology analyst who follows the company for B. Riley Securities. (Regulators in Indonesia and the Philippines have already authorized the Novavax vaccine and those countries are receiving it, under the brand name Covovax, from Serum. It will be marketed as Nuvaxovid in Europe.)

The bar for vaccine approval in Europe is high, he says—as it is with the U.S. Food and Drug Administration (FDA), where Novavax has hit roadblocks meeting that agency’s requirements for doses made within the United States. The company says it will provide the final data required for its FDA application by year’s end.

Unlike mRNA vaccines, which must be stored at subzero temperatures and used within 1 month of thawing, the Novavax vaccine can be stored unopened at refrigerator temperature (2°C to 8°C) for 9 months. That feature “allows for delivery to parts of the world where there is not a robust cold chain,” stock analyst Charles Duncan, who follows the company for Cantor Fitzgerald, wrote in a note to investors on Monday.

Vials of the Covovax vaccine
Novavax’s vaccine contains the spike protein of the pandemic coronavirus and an immune-boosting, soaplike particle.Serum Institute of India

In final results from a large North American trial published in The New England Journal of Medicine last week, Novavax’s vaccine was 90.4% efficacious in preventing symptomatic COVID-19 overall, and 100% effective against moderate to severe disease.

But the study was conducted at a time when the Alpha variant was predominant, not Omicron, which is now ascendant in most of the world. And in a different clinical trial that the company conducted in South Africa when the Beta variant represented 93% of cases, the vaccine’s efficacy dropped below 50%. Omicron shares key mutations with both Alpha and Beta, but how these will act in concert with the new variant’s myriad other mutations isn’t known.

Lab results suggesting a decline in the effectiveness of Novavax’s vaccine against Omicron were released today and echo those issued by other vaccinemakers: The Omicron variant reduced by nearly fourfold the virus-neutralizing ability of serum from people who had two Novavax shots, compared with a viral strain from early in the pandemic. But a third, booster dose “significantly” restored it by driving up antibody levels in people’s serum to levels similar to those that protected participants in the large North American trial. Novavax said it would post the underlying data on a preprint server soon.

Novavax, like other companies, is working on an Omicron-tailored version of its vaccine. On Monday it also launched a booster dose study with participants from the North American trial who will receive a third dose of either Novavax or another vaccine.

Vaccine-poor countries may eagerly take Novavax’s product, given its ease of use. In Europe, consumers may favor it because they are suspicious of products that involve genes, as the European Union’s other four COVID-19 vaccines do. “There might be some people who were really waiting for this,” says Cornelia Betsch, a psychologist who studies health communication at the University of Erfurt in Germany.

Directly using full proteins, or bits of them, from pathogens has been a vaccine approach for decades, including in the successful vaccines against the human papillomavirus and hepatitis B virus. Novavax’s vaccine uses moth cells to produce the coronavirus’ spike protein, then combines it with an immune-boosting, soaplike substance called an adjuvant.

Still, a “dead” protein-based COVID-19 vaccine isn’t a sure winner in Europe, Betsch says. A small survey her team conducted last month reveals increased resistance when the prospect of vaccination becomes imminent. In the survey, 136 unvaccinated Germans, most of whom said they had more confidence in traditional vaccines than mRNA vaccines, were split in two groups. The first was asked whether they would be willing to take a traditional vaccine in 6 months; 43% said yes. The second group was asked whether they would take one next week. The proportion saying yes fell to 31%. “In Germany [where] we struggle with low uptake, [Novavax] might not be a game changer,” Betsch says.

Novavax, which 2 years ago was moribund and was forced to sell off its manufacturing facilities, has struggled to reconstitute them during the global pandemic, despite receiving $1.75 billion in support from the U.S. government and another $399 million from the Coalition for Epidemic Preparedness Innovations. The new WHO and Commission permissions were based on a data package developed at Serum, the Indian company, which is the world’s largest vaccinemaker by volume and which has been manufacturing the vaccine for several months.  

Authorizations for vaccines made at the production facilities owned or contracted by Novavax itself in the United States and Europe aren’t guaranteed. “As these sites come online, they have to go through the same scrutiny that Serum’s data package went through,” Mamtani says.

Still, he says, the new permissions “obviously open a door for Novavax.”

Update, 22 December, 5 p.m.: This story has been updated with information about lab results from Novavax.