Update: Novavax, the non-mRNA coronavirus vaccine expected to be approved in UK

The Novavax vaccine is protein-based and uses the same platform as shots for shingles and hepatitis.

Hopefully, it will be made available for people who have a reaction to the more intrusive mRNA vaccine.

I don’t know anything more about this vaccine than what I have read, but I think it is good for people to be aware of alternatives.

My concern really is that considering the power of Pfizer, governments might well approve Novavax for ’emergency use’ but might not feel compelled to offer it as an alternative unless enough people ask for it to be an option.

And, once it does become available in various parts of the world, I can think of no reason why it should not be offered to people who want an alternative to mRNA.

Please don’t be afraid to ask your politicians or doctors if the Novavax vaccine will be made available if it is deemed to be suitable for ’emergency use.’

And if so, why not also suggest that you think it should be made available by the time you want to get your third jab.

James Porteous / Clipper Media / 19 November 2021

Novavax expected to be approved as fourth Covid vaccine in UK

24 November 2021 | Linda Geddes and Mark Brown | The Guardian

Pfizer, AstraZeneca, Moderna. Britons have become so accustomed to the three Covid vaccines available in the UK that most have forgotten about another jab, Novavax – even though the government has ordered 60m doses and hundreds of British jobs depend on it.

Late last month the US company, with a factory on Teesside primed to manufacture doses, submitted final data to UK regulators and a positive decision is anticipated within days or weeks. It will bring to an end what feels like a long wait compared to the speedy development and approval of the other jabs, including for those who took part in trials.

So what difference would this additional weapon make to the UK’s vaccination armoury? Novavax’s offering is a protein-based jab – similar to those used to protect against flu, and for routine childhood vaccination against pertussis (whooping cough) or meningococcal infection.

Other protein-based Covid vaccines are also in late-stage clinical trials, including one being developed by Sanofi and GSK, again with 60m orders from the UK. Final data from its phase 3 trial is expected any day now, paving the way for the companies to seek regulatory approval.

Whereas existing UK Covid-19 jabs instruct our cells to manufacture the coronavirus spike protein, protein-based vaccines deliver pre-made fragments of it alongside an immune-stimulating adjuvant.

Clinical trials suggest that two doses of the Novavax jab have an efficacy of about 90% against symptomatic Covid – similar to the other approved UK vaccines. It is also undergoing “mix and match” testing with the Oxford/AstraZeneca or Pfizer/BioNTech jabs and preliminary data suggest it generates a robust immune response when given as the second dose.

But it is the emerging signs of reduced side-effects that could make Novavax particularly attractive.

Trial data appear to show the potential for lower “reactogenicity” compared to existing jabs, meaning side-effects such as injection-site swelling, fatigue, headaches and muscle pain occur less frequently. No direct head-to-head comparisons have yet been done, however, and further studies are needed.

“Lower reactogenicity becomes particularly important in groups such as children, where the balance between vaccination and not vaccination becomes a little less clear, simply because, for example, in young children the likelihood of them having severe Covid-19 is so small,” said Prof Paul Heath, the director of the Vaccine Institute at St George’s, University of London, and chief investigator of Novavax’s UK trial.

However, a caveat with any new vaccine is that rarer side-effects may not become apparent until a vaccine is used widely, said Azeem Majeed, professor of primary care and public health at Imperial College London. “Post-marketing surveillance would be needed to identify any previously unknown side-effects,” he said.

The fact that it uses a more established vaccine technology could also make it more appealing. Heath said: “It may well be that those people who have been hesitant about receiving other Covid vaccines may be more open to receiving a vaccine that uses this protein adjuvant technology; it may be something that’s more familiar to them, and therefore will be happy to receive.”

Majeed is less convinced Novavax will make much difference to uptake but can see other benefits to such protein-based vaccines. It can be stored in a standard vaccine fridge at 2C to 8C, making it easier to transport and store than mRNA-based vaccines. He said: “The AstraZeneca vaccine has similar storage requirements to Novavax but the UK government seems to have largely stopped using it.”

Access to a broader range of vaccines would also be helpful if regular booster shots are needed in the future. “Because of Novavax’s simpler storage requirements, it would be easier to use in GP surgeries and pharmacies,” said Majeed.

This combination of easier transport and storage is even more important in developing countries, where low temperature-controlled supply chains are less well established. “Worldwide, the more vaccines the better, particularly if they are low cost and don’t require freezing for storage and delivery,” said Brendan Wren, professor of microbial pathogenesis at the London School of Hygiene and Tropical Medicine.

Jobs could come alongside the new jab, too: in March, Boris Johnson announced that 60m doses would be made in north-east England. Fujifilm Diosynth would manufacture them at its plant in Billingham, while GSK would fill and finish them – package them up in vials – at its operation in Barnard Castle.

About 300 people at FujiFilm are said to have been working on the vaccine, though delays had prompted concerns that jobs would be hit. Fujifilm last month said manufacturing was unaffected by the delay, and they plan to expand their workforce in the years to come.

The local Labour MP, Alex Cunningham, who represents Stockton North, met with a representative of Novavax and said he felt reassured. “I don’t know how long the approvals process will take but hope production will get up and running soon,” he said.

The Novavax jab has already been approved for use in the Philippines and Indonesia. On 4 November, the company submitted an emergency use application to the World Health Organization. If approved, it would be the first protein-based vaccine to be recommended by the WHO.

Novavax told the Guardian that it was now routinely producing high-quality product at commercial scale at multiple sites across the world. The Serum Institute of India is also manufacturing doses, 20m of which have been approved for export to Indonesia.

Silvia Taylor, the senior vice-president of global corporate communications and investor relations at Novavax, said: “Now that the submission [to the UK Medicine and Healthcare products Regulatory Authority] is complete, the timeline is in the hands of the regulatory agencies.”

Novavax COVID vaccine is nearing approval – but what impact will it have?

18 November 2021 | Michael Head | The Conversation

The pandemic has been rumbling on for two years and is probably going to rumble on for years to come. And despite recent excitement about new drugs to treat COVID, it’s still vaccines that will underpin each country’s route out of the pandemic.

Immunisation has proven a highly effective way of stopping people from developing severe COVID. Vaccines can be given to large numbers of people to offer long-term protection in a way that other treatments, such as antiviral drugs, can’t. Vaccines also reduce the risk of getting infected and passing the virus on.

Many different vaccines are now available globally, with billions of doses administered. Yet because they’ve been unequally bought up, with richer countries capturing the lion’s share, only half the world has received at least one COVID vaccine dose.

So it’s good that there are additional vaccines showing promise that could soon be widely available to boost supplies – such as Novavax’s.

How this vaccine works

The Novavax jab is a protein subunit vaccine, and so is different from the mRNA vaccines developed by Moderna and Pfizer, the viral-vectored vaccines made by AstraZeneca and Johnson & Johnson, and the inactivated-virus vaccines made by Sinovac and Sinopharm.

Protein subunit vaccines contain a key part of whatever it is that they protect against. In this case, to protect against the coronavirus, they contain the spike proteins that cover the virus’s surface, which the immune system can easily recognise. When the real virus is encountered in the future, the immune system has defences that are trained to attack these outer parts of the virus and quickly destroy it.

An illustration of the surface of the coronavirus, with its spike proteins highlighted
Rather than present the body with the whole virus, the vaccine contains just copies of its spike proteins (pink). Design_Cells/Shutterstock

The spike proteins – by themselves harmless, being incapable of causing a COVID infection – are manufactured, intriguingly, within moth cells. The proteins are then purified and added to an adjuvant, an ingredient that enhances the immune response. The adjuvant here is made from an extract from the soapbark tree.

This subunit approach isn’t new. Vaccines for human papillomavirus and hepatitis B have used similar methods. Both are safe and effective.

The Novavax COVID vaccine also looks like it performs well. In phase 3 trials (the final phase of testing in humans) it was 90% protective against developing symptomatic COVID, with no severe cases reported among those receiving the vaccine (and thus, in essence, 100% protection against hospitalisation and death was observed). Its safety profile appears to be at the very least comparable, if not better than, the Pfizer and Moderna vaccines.

These published analyses pitted the vaccine against the alpha and beta variants, but not delta. However, a press release covering a trial investigating the use of Novavax as a booster suggests it’s highly effective at generating antibodies, including against delta.

What effect will it have?

Novavax’s vaccine looks like a very exciting product, but its future depends on it being authorised by some of the world’s key regulators.

It has received emergency use authorisation in Indonesia and the Philippines, and has completed submissions for regulatory approval to the UK, the EU regulator, Canada and also to the World Health Organization (WHO), which covers recommendations for low-income countries. Further submissions are expected to follow in other countries, including New Zealand and the US.

In the short term, most richer countries have significant stocks of existing vaccines, meaning their immediate rollouts and booster programmes are probably covered. The longer-term need for further doses in these countries is uncertain.

However, if the vaccine became available in rich countries, it could be a useful tool for reaching the vaccine hesitant. Some people who have avoided the newly developed mRNA and viral-vectored products due to safety concerns have said they would take a vaccine like Novavax’s that’s based on a more traditional method.

But the most appropriate use of Novavax over the next year or two would be to help reduce the extensive COVID vaccine inequity that exists. Only 6% of the population of sub-Saharan Africa has received two doses of any COVID vaccine. In low-income countries, less than 5% have received even one dose.

The Novavax vaccine also only needs to be refrigerated rather than frozen for storage, making it an attractive product for low-income countries. Yet to reach these countries it would probably need to be distributed through the global vaccine-sharing scheme, Covax, and getting the vaccine authorised by the WHO is a prerequisite for this.

Plus, there remain concerns that high-income countries will buy up most of the doses, regardless of their need for them. The UK, for example, has 60 million doses on order, and deals with the US and EU for 100 million and 200 million doses respectively. It’s unlikely these countries will have a genuine need for them. There simply has to be improved global sharing of available supplies.

Indian prime minister Shri Narendra Modi visiting the Serum Institute of India
The Serum Institute of India – the biggest vaccine manufacturer in the world – will be a producer of the Novavax vaccine. YashSD/Shutterstock

A further issue is that the company has reportedly struggled with the manufacturing process, with doubts raised about its ability to produce the vaccine in large quantities. It’s believed that this is the main reason its submissions for regulatory approval have been delayed. It had expected to file for authorisation in the first half of 2021.

India, though, may come to the rescue here. The Serum Institute of India will make the Novavax doses that will be supplied to Indonesia, and it has already ramped up production of other vaccines licensed to it for production – in particular the AstraZeneca vaccine. The institute is reportedly producing 240 million doses of COVID vaccines each month.

Having additional safe and effective vaccines will be vital to minimising the future impact of COVID. Novavax looks like a very helpful product, but from a global perspective, hopes rest on its approval by the WHO and on supplies being available. Other countries will be following the WHO’s decision making – and the vaccine’s performance in Indonesia and the Philippines – with great interest.

14 November 2021 | ALEXI COHAN | Boston Herald

Maryland-based biotech company Novavax could soon bring a new coronavirus vaccine into the market about a year after Americans first rolled up their sleeves.

The following include reader questions about the vaccine along with a few others compiled by the Herald and/or Novavax.

When can I get a Novavax coronavirus vaccine?
The vaccine, called NVX-CoV2373, is not currently available in the United States. The company expects to submit data to the Food and Drug Administration by the end of the year. Once authorization is requested, a rigorous review process will take place before the shot is cleared for use in the general public.

What makes this coronavirus vaccine different from the ones we already have?
The Novavax vaccine is protein-based and uses the same platform as shots for shingles and hepatitis. The proteins deliver immune stimulation directly into a person’s cells as opposed to a fragment of genetic code. It is not an mRNA as is the case with Moderna and Pfizer, or an adenovirus vector, such as the Johnson & Johnson vax.

How does it work?
The Novavax coronavirus vaccine is engineered from the genetic sequence of coronavirus with nanoparticle technology. The technology binds with human receptors targeted by virus which is critical for effective protection. When the vaccine is injected, it stimulates the immune system to produce antibodies.

Is it safe and effective?
Clinical trials for the Novavax shot have shown an overall 90% efficacy against coronavirus and 100% protection against moderate and severe disease. Most common side effects include injection site pain and tenderness, fatigue, headache and muscle pain. No single adverse reaction was reported by more than 1% of trial participants.

Can foreign travelers show proof of the Novavax vaccine to enter the United States?
Yes. Novavax clinical trial participants from sites outside the U.S. are considered fully vaccinated if they received the same product that was administered in the U.S. clinical trials. It is one of the vaccines already approved by the Centers for Disease Control and Prevention for air travel in the U.S., giving the 30,000 in the trial for the jab a passport to move around, whereas other shots haven’t made the cut.

Could children get this vaccine?
The vaccine is not yet authorized for use in the United States, but Novavax initiated a pediatric expansion of a phase 3 clinical trial in May 2021 for children ages 12-17. The company intends to pursue authorization in that age group and younger age groups.

How is it administered?
Two doses are given three weeks apart.

A participant in Novavax’s phase III trial receives a jab in early 2021.Credit: Kenny Holston/The New York Times/eyevine

How protein-based COVID vaccines could change the pandemic

11 November 2021 | Elie Dolgin | Nature

Pamela Sherry is eager to become immunized against COVID-19. But she has put off getting a jab.

“I believe vaccines work,” she says. “I want the protection.” Yet she is prone to acute immune reactions and has blood circulation problems, so she has concerns about the shots available in the United States, where she lives — those based on messenger RNA (mRNA) and viral-vector technologies. Although safe for most of the population, they have been linked to rare but potentially severe side effects, including heart inflammation and blood clots.

So Sherry has been waiting for the menu of vaccine options available to her to expand. In particular, she is holding out for a vaccine built from purified proteins.

Unlike the relatively new technologies that the mRNA and viral-vector COVID-19 shots are based on, protein vaccines have been used for decades to protect people from hepatitis, shingles and other viral infections.

To elicit a protective immune response, these shots deliver proteins, along with immunity-stimulating adjuvants, directly to a person’s cells, rather than a fragment of genetic code that the cells must read to synthesize the proteins themselves.

Although protein vaccines are not yet in widespread use for COVID-19, late-stage clinical-trial data so far look promising, demonstrating strong protection with fewer side effects than other COVID-19 shots typically cause.

If such a shot were available, “I would go and get it right away,” says Sherry, who runs a stationery business out of her home in Prosper, Texas.

Sherry’s wait could soon be over. After months of quality-control setbacks and manufacturing delays, executives at biotechnology firm Novavax in Gaithersburg, Maryland, say they are poised to submit the company’s long-awaited application for their protein-based vaccine to US drug regulators before the end of the year.

(On 1 November, Indonesia granted the company’s vaccine its first emergency authorization, and regulatory filings have already been made with government agencies in Australia, Canada, the United Kingdom, the European Union and elsewhere.)

Meanwhile, two vaccine makers in Asia — Clover Biopharmaceuticals, based in Chengdu, China, and Biological E in Hyderabad, India — are similarly on track to file with various national authorities in the coming weeks and months.

Protein vaccines 101: An infographic that shows how COVID-19 protein-based vaccines are made, and how the body reacts to them.
Nik Spencer/Nature

In a few corners of the globe — Cuba, Taiwan, and elsewhere — home-grown protein shots are already playing a role in national vaccination efforts. Now, with a wave of more such products up for approval, the shots could allay the fears of vaccine hold-outs such as Sherry, serve as booster shots, and, importantly, help to fill a void in the global pandemic response.

So far, fewer than 6% of people in low-income countries have been vaccinated against COVID-19. Protein-based vaccines — with their inexpensive production protocols and logistical advantages, including stability at a broad range of temperatures — could help to narrow the immunization gap between rich and poor countries.

“The world needs these protein-based vaccines to reach those vulnerable populations,” says Nick Jackson, head of programmes and innovative technologies at the Coalition for Epidemic Preparedness Innovations, which has invested more than US$1 billion in five protein-based COVID-19 vaccines in active development.

The lion’s share is going to products made by Clover, Novavax and SK bioscience in Seongnam, South Korea. “Protein vaccines are going to beckon in a new era of COVID-19 immunization,” Jackson says.

Intrinsically slow

From the earliest days of the pandemic response, researchers anticipated that protein-based designs would be slower off the blocks than other vaccine technologies.

Companies know how to manufacture gobs of purified protein at scale — using genetically engineered cells from mammals, insects or microbes — but the process involves many steps, each of which has to be optimized for making a specific protein.

“There’s an intrinsic slowness,” says Christian Mandl, a former industry executive who now consults on vaccine-development issues. Most of the protein-based vaccines currently in testing have been crafted around some version of the coronavirus SARS-CoV-2’s spike protein, which helps the virus to enter cells (see ‘Protein vaccines 101’).

Aside from the expected delays, however, vaccine manufacturers made some avoidable errors. When drug giants Sanofi and GlaxoSmithKline (GSK) teamed up on a protein vaccine project, for example, onlookers expected clinical development to move with great haste.

But the companies initially relied on faulty reagents to characterize their product, resulting in a dosing miscalculation. Early trial participants received doses that were approximately one-fifth of the planned dose.

The mistake cost Sanofi and GSK around five months in their development timeline, because they had to repeat an exploratory study to find the optimal dose for late-stage testing. Their protein-based jab is now in a phase III trial that kicked off in late May, which involves thousands of participants in Africa, Asia and Latin America.

By comparison, large-scale trials from Novavax and Clover have already yielded efficacy data. According to a preprint published last month (that has not been peer reviewed)1, the Novavax jab offered more than 90% protection against symptomatic COVID-19 in a 30,000-person study completed early in the year — before the Delta variant arrived, when only milder forms of the virus were in circulation.

Clover reported somewhat lower efficacy results for its protein-based jab — just 67% for symptomatic COVID-19 of any severity — but that number was probably deflated, because the vaccine was tested on populations grappling with more virulent strains of SARS-CoV-2, including the Delta and Mu variants. Both vaccines elicited antibody levels on par with those induced by mRNA shots, which have emerged as some of the most efficacious in the pandemic2,3.

The results show that making COVID-19 vaccines using proteins “is not a substandard approach just because it took longer,” says Ryan Spencer, chief executive of Dynavax Technologies of Emeryville, California, which makes the Clover vaccine’s adjuvant.

The shots also appear to be safe. None of the 50 or so protein-based COVID-19 vaccines now in clinical testing around the world have elicited any major side effects.

Even many of the reactions typically elicited by the mRNA or viral-vector jabs — headaches, fevers, nausea and chills — have proven far less common with the protein-based alternatives.

For example, less than 1% of individuals who received a protein-based shot from Taiwan’s Medigen Vaccine Biologics Corporation, in Taipei City, developed fevers in clinical studies.

“The safety profile is very much like those of influenza vaccines,” says Szu-Min Hsieh, an infectious-disease specialist at the National Taiwan University Hospital in Taipei, who published phase II trial results last month4.

“That’s going to allow a lot of people not to fret as much,” adds Cindy Gay, an infectious-disease physician at the University of North Carolina School of Medicine in Chapel Hill, who co-led testing of the Novavax vaccine.

Design differences

Even if one protein-based vaccine succeeds — both in terms of its performance and in finding a market — there’s no reason to think they all will, however.

For one thing, the form of the spike protein they deploy varies greatly from one product to the next. Some use single proteins, others triads. Some use full-length spike protein, others just a fragment. Some proteins are free-floating, others are packaged together into nanoparticles.

Many of them are also manufactured using different types of cell (see ‘Ones to watch’). Novavax and Sanofi/GSK use cells from the fall armyworm (Spodoptera frugiperda), a type of moth, to synthesize protein; Clover and Medigen rely on hamster ovary cells, a mainstay of therapeutic antibody production in the biotechnology industry. Plus, the leading candidates rely on different adjuvants, each of which prods the immune system in its own way, resulting in different kinds of vaccine responses.

All of this could translate into different efficacy and safety profiles, says Thomas Breuer, chief global health officer for GSK. “I could imagine that you will see differences, but time and the phase III trial results will give us the ultimate answer.”

Those results have the potential to shape booster programmes in wealthy countries, where large percentages of the population have already been vaccinated. Although mRNA jabs are currently being used as boosters in many of these places, tolerability concerns could drive people to seek out protein-based boosters once they’re available.

The technology is tried and true, and studies have shown that a mix-and-match strategy — in which a different COVID-19 vaccine is administered after the first — are effective at preventing the disease, notes John Mascola, director of the Vaccine Research Center at the US National Institute of Allergy and Infectious Diseases. “We would need to see human data” confirming such a protein-based booster regimen is similarly safe and effective, Mascola says — but he and others expect that it will be. Trials evaluating the approach are ongoing.

Plugging the equity gap

Once authorized, protein shots are also expected to rapidly address supply shortages that have plagued efforts to vaccinate lower-income countries. Novavax and Clover, for example, have each pledged to donate hundreds of millions of doses of their jabs next year to COVAX, an initiative designed to distribute vaccines around the world.

The global health community has also been arguing that equitable access to COVID-19 vaccines could be achieved through local manufacturing of shots in the global south. To achieve this, more researchers should be looking to simple, inexpensive production systems that manufacturers in less-wealthy countries can readily implement, says Christopher Love, a chemical engineer at the Massachusetts Institute of Technology in Cambridge.

Biological E is already taking advantage of one such system — yeast — to manufacture the vaccine it licensed from Baylor College of Medicine in Houston, Texas. According to Maria Elena Bottazzi, a Baylor virologist who helped to create the product, that makes it “probably the easiest and cheapest to scale” of all the COVID-19 vaccines on or nearing the market today.

In the earliest days of the COVID-19 crisis, vaccine platforms such as mRNA brought the advantage of speed, says Ralf Clemens, a vaccine-industry veteran and a scientific adviser to Clover. But now that a wave of protein-based vaccines is coming, he says, they will have a lot more to offer — and in the long run when it comes to protecting the world against coronavirus infections, “I think they will prevail.”

Novavax COVID-19 vaccine gets first authorization; expects more within weeks, CEO says

01 November 2021 | Carl O’donnell and Dania Nadeem | Reuters

Nov 1 (Reuters) – Novavax Inc (NVAX.O) expects regulators in India, the Philippines and elsewhere to make a decision on its COVID-19 vaccine within “weeks,” its chief executive told Reuters, after the shot on Monday received its first emergency use authorization (EUA) from Indonesia.

Novavax shares were up about 13% after the company also said it had filed an application for emergency use of the vaccine to Canada and the European Medicines Agency.

For Indonesia, the shot will be manufactured by the world’s largest vaccine manufacturer, Serum Institute in India (SII), and sold under the Indian company’s brand name, Covovax. Novavax said initial shipments into Indonesia are expected to begin imminently.

The World Health Organization (WHO) is also reviewing Novavax’s regulatory filing and the U.S. drugmaker expects that review to be resolved in the coming weeks, Chief Executive Stanley Erck told Reuters in a phone interview on Monday.

A green light from the WHO would set the stage for Novavax to begin shipping doses to the COVAX program that supplies shots to low-income countries. Novavax and SII have together committed to provide more than 1.1 billion doses to COVAX, which is co-led by the WHO.

“I think we’ll get some doses to COVAX this year,” Erck said. “But I think (Novavax is) going to really start being able to ship large quantity to COVAX in the first quarter” of 2022.

Erck said Novavax has resolved all of its manufacturing challenges and does not expect regulators to have any further concerns about its production processes.

He said Novavax is “in dialogue with the U.S. FDA and … we expect a full submission within the next several weeks.”

Novavax had delayed filing for U.S. approval, and Politico reported last month that the company faced production and quality problems.

SII is authorized to make the Novavax vaccine and the U.S. company said it will apply for regulatory authorization for other facilities, such as its plant in the Czech republic, in the coming weeks.

Indonesia is slated to receive 20 million doses of the protein-based vaccine this year, according to the government.

Penny Lukito, chief of the National Agency for Drug and Food Control of Indonesia, did not immediately respond to a Reuters request for comment.

Novavax has so far applied for EUA in various countries, including the UK, Australia, India and the Philippines.

“It will be weeks, not months, for them to review” Novavax’s regulatory submissions and potentially clear the shot for use, Erck said.

The company, along with Japanese partner Takeda Pharmaceutical Co (4502.T), said on Friday it was preparing to seek regulatory approval for a rollout in Japan early next year. read more

The Novavax shot was shown to be more than 90% effective, including against a variety of concerning variants of the coronavirus in a large, late-stage U.S.-based trial.

Reporting by Dania Nadeem in Bengaluru and Carl O’Donnell in New York; additional reporting by Leroy Leo in Bengaluru and Stanley Widianto in Jakarta; Editing by Maju Samuel and Bill Berkrot


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