Novavax highly protective against Kent variant but less against SA variant

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The Novavax vaccine is highly protective of the Kent variant of COVID-19 but less so against the South African variant, writes MedicalBrief. “At the moment it is the only vaccine showing objective efficacy against the South African variant,” said Wits University's Prof Shabir Madhi, while noting that data showed a high risk for patients infected by the original coronavirus infection to be re-infected by the variants.

The Guardian reports that the Novavax vaccine, which has been going through late-stage trials in the last few months, is highly protective against variant of coronavirus that emerged in Kent in the UK.  It also gives some protection – though less –  against the variant causing even more concern in South Africa, which scientists think may be capable of evading the vaccines currently in use.

The study in South Africa was an earlier stage 2 trial and did not show such strong results. About 90% of the cases identified among participants in the trial were caused by the variant. There were 15 cases identified among people given the vaccine and 29 in the placebo group, giving an efficacy of 60%. About a third of the participants had antibodies, believed to have been a result of previous infection by the original coronavirus, which had not protected them against the variant.

The report says Novavax now plans to design a vaccine specifically to work against the variant in South Africa.

“The 60% reduced risk against COVID-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally,” said Professor Shabir Madhi of University of the Witwatersrand, principal investigator in the trial in South Africa.

The Guardian reports that the Novavax vaccine is different from the Oxford/AstraZeneca or the Pfizer/BioNTech vaccines. It contains spike proteins, produced by moth cells infected with a genetically modified virus, together with a substance called an adjuvant which boosts the immune response.

However, like the Oxford/AstraZeneca jab it can be stored at between 2 and 8C, meaning it requires only normal refrigeration, making it easier to deliver it to patients.

 

Stat News reports that it’s unclear whether these data will be enough for US approval, or if the US will wait for further data, as it appears to be doing with vaccines developed by AstraZeneca and Oxford University. Novavax said it expects to file for an emergency authorization in the UK in the coming months, once it has final data from its clinical trial there. The company said it has been in contact with the US Food and Drug Administration but didn’t provide details on its plans.

Carlos del Rio, a professor of infectious diseases at the Emory University School of Medicine, said the overall efficacy numbers were impressive, and that the vaccine showed at least some efficacy against the variant first identified in South Africa.

By the same token, the lower efficacy against that variant could be a vulnerability in the US, where it was first reported in South Carolina, and elsewhere.

Nahid Bhadelia, medical director of the special pathogens unit at Boston Medical Centre, emphasised that although the drop in efficacy against the South African variant is bad news, the results aren’t “a complete wash.” The vaccine, she said, “can still make a huge difference.” But the results also emphasise the important work of figuring out how to develop booster shots against new variants, especially given the news that the South Africa strain, B1351, was found in South Carolina.

Novavax said it is already at work on a new version of the vaccine designed to combat more infectious strains of SARS-CoV-2, which could work as a booster shot for people already inoculated. But clinical testing isn’t expected until the second quarter of this year.

Some experts cautioned against over-interpreting the efficacy results in the South Africa trial, noting that they amounted to a relatively small number of cases in a preliminary analysis.

“I am not sure that it is disappointing. The UK data look very good. The South Africa data may be more nuanced,” said Anna Durbin, a professor at the Johns Hopkins Bloomberg School of Public Health, noting that each trial defined symptomatic disease slightly differently. She said she would be interested in seeing more data on the severity of disease in the cases reported.

Scott Gottlieb, the former FDA commissioner and Pfizer board member, said he didn’t think it was a surprise that the vaccine was less effective against the new strain. “We have already seen experimentally that there is a falloff in neutralization against that variant with the other vaccines, and we should expect that this may be common to all the vaccines that use the original spike protein as the epitope, regardless of how that protein is being delivered,” he said.

Stat News reports that more data will be available with results from Johnson & Johnson, because that trial will include patients from both Brazil and South Africa.

“I think this raises the stakes on putting boosters into development that are based on these new variants, and building a regulatory process that allows this sort of incremental, follow-on innovation to reach the market based on something short of brand new, full-blown outcomes studies,” Gottlieb said.

 

Madhi revealed that their data showed there was a high risk for patients who had been infected by the “original” coronavirus infection to be re-infected by the mutated South African and UK strains.

Daily Maverick reports that after weeks of uncertainty and speculation, Madhi announced that their vaccine is the first that has shown high levels of efficacy against the South African strain of the coronavirus as well as the UK variant.

Describing the result of 60% protection against the virus as something he did not dream they would obtain, Mahdi recounted their quest to find a vaccine effective against the South African mutation of the virus – one that mutated to make it even more contagious.

“Sixty percent was something I did not dream of when we saw how poorly natural immunity fared against the South African variant. It might sound disappointing but it is …also about coverage. We must also look at public health impact,” he said.

He said Novavax now plan to create a vaccine that will include both the “original” virus and the South African mutation within the next few months.

“At the moment it is the only vaccine showing objective efficacy against the South African variant,” he said.

Mahdi has previously explained that the Novavax vaccine uses “a more tried-and-tested approach” taking the (spike) protein of a coronavirus and injecting that into the individual, causing an immune response that will destroy the virus.

 

Protein-based coronavirus 2019 (COVID-19) vaccine candidate NVX-CoV2373, from Novavax, has reported phase 3 findings showing 89.3% efficacy in prevention of COVID-19 in participants from the UK, reports Contagion Live.

The trial findings – conducted at a time of significant transmission in the country and an emerging, more transmissible variant spreading globally – coincide with phase 2b findings which show lesser prevention of the variant originally observed in South Africa.

The Vaccine
NVX-CoV2373 is a vaccine comprised of a full-length, prefusion spike protein made of proprietary recombinant nanoparticle technology and the saponin-based Matrix-M adjuvant.

Produced in insect cells, the purified protein is encoded by the SARS-CoV-2 spike protein genetic sequence.

With the emergence of new mutated strains of SARS-CoV-2 in regions including southeast England and South Africa, Novavax has begun development of new vaccine constructs specified to the strains’ genetic codes, with expectation that ideal candidates provided via booster or in combination as a bivalent vaccine will become apparent in the coming days.

Testing for these newer vaccines would launch in the second quarter of 2021.
“A primary benefit of our adjuvanted platform is that it uses a very small amount of antigen, enabling the rapid creation and large-scale production of combination vaccine candidates that could potentially address multiple circulating strains of COVID-19,” said Dr Gregory M Glenn, Novavax president of research and development.

UK Trial
Investigators enrolled 15,000-plus adult participants aged 18-84 years old, to assess the vaccine for a primary endpoint of occurrence of PCR-confirmed, symptomatic COVID-19 with onset at least 7 days following the booster vaccine dose in participants serologically negative for SARS-CoV-2 at baseline.

More than one-fourth (27%) of trial participants were older than 65 years.

In the first interim analysis of 62 COVID-19 cases, 56 (89.2%) were observed in the placebo arm, versus just 6 in the vaccine group (95% CI, 75.2 – 95.4). Of the 62 cases, just 1 was severe – from a placebo patient.

The highly transmissible UK variant strain was detected in more than half of all observed cases, investigators noted (n = 32). In a post hoc assessment, investigators reported that NVX-CoV2373 was 95.6% efficacious against the original COVID-19 strain, and 85.6% efficacious versus the UK variant strain.

In an interim analysis of the safety database, investigators observed low, balanced rates of severe and medically-attended adverse events in both treatment arms.

Clive Dix, chair, of the UK Vaccine Taskforce, praised the results as “spectacular,” and expressed encouragement for the slightly less efficacious effect observed against the UK variant with the vaccine.

“This is an incredible achievement that will ensure we can protect individuals in the UK and the rest of the world from this virus,” Dix said. “Novavax expects to share further details of the UK trial results as additional data become available.”

South Africa Trial
In the phase 2b clinical trial assessing the vaccine versus placebo in 4400-plus adult participants from August 2020 to mid-January 2021, investigators reported a 60% efficacy (95% CI, 19.9 – 80.1) in prevention of COVID-19 among participants who were HIV-negative.

Overall, they observed 29 cases in the placebo group, and 15 in the NVX-CoV2373 group. Again, only 1 severe case was reported in the placebo group.

In the overall trial population, comprised of both HIV-positive and HIV-negative participants, investigators reported a 49.4% efficacy (95% CI, 6.1 – 72.8). Preliminary sequencing data show that, for 27 of the observed 44 total COVID-19 diagnosis, 92.6% of cases were the South Africa variant.

Investigators stressed, however, that one-third of enrolled participants were seropositive, demonstrating prior COVID-19 infection at baseline. Pre-trial infections, per temporal epidemiology data for the assessed region, indicate these cases would be the original COVID-19 strain.

Whether the current Novavax product could completely protect against the globally-spreading South Africa variant is questionable, yet investigators stress its value in reducing COVID-19 severity.

“The 60% reduced risk against COVID-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally,” Madhi said. “This is the first COVID-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa.”

US Trial
According to Novavax, the enrolling PREVENT-19 clinical trial in US and Mexico has already randomised more than 16,000 participants, with expectation of 30,000 targeted enrolment by early February.

Conducted in support from federal agencies including Operation Warp Speed (OWS), the phase 3, randomised, placebo-controlled, observer-blinded assessment will gauge the efficacy, safety, and immunogenicity of NVX-CoV2373 with Matrix-M in adults versus placebo.

 

Full report in The Guardian (Open access)

 

Full Stat News report (Open access)

 

Full Daily Maverick report (Open access)

 

Contagion Live material

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