South African President Cyril Ramaphosa and Deputy President David Mabuza visit an Aspen Pharmacare facility in March 2021, a key partner in the country’s J&J vaccine drive.

A new South African study shows that a second Johnson & Johnson dose, administered 6-9 months after the initial single-dose vaccine provided 84% protection against hospitalization from the Omicron SARS-CoV2 variant – results that even outperformed those of an earlier South African study looking at effectiveness of the two-dose Pfizer regime in the face of Omicron.

The study, published in the medrxiv.org preprint server on Thursday,  measured the vaccine’s effectiveness in a group of some 227,000 health care workers, including 69,000 people who received the vaccine booster, between 8 November and 17 December – just as the Omicron variant was taking hold in the country.

The study found that vaccine efficiency against hospitalizations increased over time since the booster dose was administered from 63% in the first to weeks, to 85% post-boost.

“This data is important given the increased reliance on the Ad26.COV.2 [J&J] vaccine in Africa,” said the team of researchers, led by scientists at the South African Medical Research Council, the Desmond Tutu HIV Centre, and other prominent research centers.

Previous large-scale South African study on two Pfizer jabs yielded weaker results

A University of Michigan researcher administers the Johnson & Johnson COVID-19 vaccine candidate during phase 3 clinical trials in the US and seven other countries. The vaccine was authorized in February 2021 by the US FDA.

The study contrasts with a 14 December report on Pfizer vaccine efficacy in the face of Omicron by one of South Africa’s largest insurance providers.

The study by Discovery Health,  found that a two-dose Pfizer-BioNTech vaccine provided 70% protection against severe COVID cases, requiring hospitalizations, but only 33% protection against COVID infection during the current Omicron wave. The study examined some 211,000 COVID-19 test results obtained between 15 November and 7 December, 41% of which were from adult members who had received two-doses of the Pfizer vaccine.

Although the U.S. Food and Drug Administration was one of the first regulatory agencies to authorize the Johnson & Johnson/Janssen COVID-19 vaccine in February 2021, and following that, a booster shot, the vaccine had fallen from favour more recently in the United States. And that was following warnings from the US Centers for Disease Control and Prevention about rare but life-threatening blood clots that could be linked to the vaccine.

The South African Medical Association in November also had protested the exclusive arrangements between Johnson & Johnson and the government which led to health workers having only one booster option – a second J&J jab – while the company ran research on the results.

Latest South African results – turn earlier assumptions on head

Johnson & Johnson can ship vaccines standard cold chain technologies, because the temperature requirements are not as strict as for Pfizer’s and Moderna’s vaccines.

At the time, the South African Medical Association complained that the Pfizer jabs appeared to generate a more robust response – and should thus also be made available to highly exposed health workers.

Now, those assumptions may be turned on the head.

The J&J vaccine has been an anchor of the South African vaccine response from the beginning of vaccine rollouts – where the jab is also being produced in a collaboration with Aspen Pharmaceuticals for domestic use – as well as for the wider African market.

Along with stimulating a high degree of response with the first shot, the J&J vaccine can remain stable for up to three months at  2°C to 8°C, while the Pfizer and Moderna mRNA vaccines require cold chain storage at -28°C to 70°C.

The J&J vaccine uses a inactivated adenovirus  (cold virus) to deliver a genetic fragment of the SARS-CoV2 spike protein into the body, which in turn stimulates immune response.

In contrast, the Pfizer and Moderna vaccines deliver messenger RNA (mRNA) – a single strand genetic instruction making part of a SARS-CoV2 spike protein – into the body.  And that mRNA triggers and immune response.

Unexpectedly potent T Cell responses to Omicron Variant

In another a pre-print laboratory study published on 26 December, South African researchers also found that T-cells taken from people who received Johnson & Johnson vaccines recognized Omicron-infected cells almost as well as they recognized cells infected with other variants. That study is also significant as it suggests that even if antibody response to Omicron is not as robust in vaccinated individuals, the other critical factor in the body’s immune response remains more resilient.

“We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations,” wrote the authors, led by scientists at the University of Cape Town.

See here a video about how the four main categories of SARS-CoV2 actually work:

https://youtu.be/lFjIVIIcCvc

Image Credits: Johnson & Johnson, NBC News.

WHO Director General Dr Tedros Adhanom Ghebreyesus, at WHO end-year press conference marking two-years since the first reports of the novel coronavirus circulating in Wuhan, China were picked up by WHO.

As the world marks two years since the emergence of the first reports about a “novel coronavirus” circulating in Wuhan China, countries in Europe, North America and elsewhere are facing yet another “tsunami” of infections – this time driven by the highly-infectious Omicron variant, warned WHO Director General Dr. Tedros Adhanom Ghebreyesus. 

He spoke at a press conference Wednesday marking two years since the first public message about the emergence of the coronavirus was posted on 31 December by the Wuhan Municipal Health Commission – delivered by WHO’s China country office to Geneva headquarters.  On that same day, Taiwan also conveyed private messages to WHO about the Wuhan outbreak that its surveillance had identified.  

Fast-forward to December 2021,  and some 5.3 million people have died so far this year – more than double the death toll of last year, noted Ghebreyesus.

And while the new SARS-CoV2 Omicron variant may be yielding lower rates of serious cases, the sheer numbers of infections being recorded every day could still lead to major hospital overloads – particularly in European countries that are seeing some of the  highest rates ever of new infections, Tedros and other senior WHO officials warned.  

But they also held out hope that the pandemic could also be finally squelched in 2022 – if enough of the world’s expanding vaccine supplies could be directed to reach underserved countries and populations that have vaccinated less than 50 percent of their eligible population – ripe ground from which new variants could emerge. 

“I ask everyone to make a New Years Resolution to get behind the campaign to vaccinate 70% [globally] by July 2022. We have 185 days to the finish line,” said the WHO Director General, repeating an oft-stated mantra that vaccine inequities are prolonging the pandemic.  

‘Dual Track’ pandemic 

Dr. Mike Ryan, Executive Director of Health Emergencies, WHO, at 29 December WHO press conference marking 2 years since the emergence of the novel coronavirus.

While seemingly milder omicron infections are soaring among younger people, the virulent Delta variant of the virus is still causing considerable hospitalizations and severe disease, particularly  among older people, and the unvaccinated, said Mike Ryan, WHO’s Executive Director of Health Emergencies.

“What we’re seeing is this dual circulation. We’re seeing a well established Delta wave,  and that’s affecting all age groups, and particularly causing a lot of hospitalizations and severe disease among older persons and more vulnerable groups, particularly the under-vaccinated or unvaccinated…. 

“Then we have this emerging Omicron wave which has primarily begun amongst younger people, reflecting social mixing patterns… It’s moving slowly into older age groups now.

“And I think the big question in my mind is: will the virus behaviour look milder [in those older and more vulnerable groups]? 

“It looks like it’s causing a milder disease, on the face of it looking at the population that’s  infected. But what we haven’t seen is the omicron wave fully established in the broader population.  

“And I’m just I’m a little nervous to make positive predictions until we see how well the vaccine protection is going to work in those older and more vulnerable populations – to see whether previous infection or vaccination is going to provide the same levels of protection against severe disease and hospitalizations [as it did in the case of Delta]. 

“Or is this virus inherently less virulent in any case, in its own right?” Ryan asked.

Case declines in South Africa – but that’s not necessarily a weathervane for Europe 

In response to Omicron, South Africa initiated boosters and increased its vaccination drives- but new cases have recently declined sharply.

In fact, South Africa has seen a sharp decline, 29% in Omicron cases over the past week, as well as consistently lower rates of hospitalization from Omicron in comparison to infections caused by the Delta variant.  And these are indeed hopeful signs, Ryan said. 

But it’s not clear to what extent Europe, which has an older population, which has been less exposed to the virus overall, will follow those same encouraging trends, he added:    

“It remains to be seen in the coming weeks. I think we will still see that decoupling from cases and severe disease will be sustained in Europe. 

“But with the sheer numbers of cases that we’re likely to get associated with the Omicron variant, that growth rate in the number of cases per day will ultimately generate sick people who will need to be admitted to hospital and could potentially die. 

“I don’t think anyone is certain as to how this is going to play out. And that’s why caution right now, with getting exposed, and protecting those people in our population most likely to get the disease, physical protection, vaccine protection and then going by the public health advice in each jurisdiction. I think it’s really important over the coming weeks to suppress transmission of both variants to the minimum until we can until we see what is the impact of this virus [variant] in those older and more vulnerable populations.”

European countries applying stricter measures 

Frankfurt Germany. A bike path sign noting mask requirements for cyclists lies askance. In a replay of winter 2020, Germany and other European countries have again imposed strict restrictions on businesses, culture, travel and social gatherings.

Indeed, most European countries – where infection rates are among the world’s highest once more this winter – have responded with a suite of new restrictions on social gatherings, cultural events, and businesses.  

Those have ranged from Germany’s limitation on  private social gatherings to just ten people to a French call for people to to work from home wherever possible. 

The Netherlands has imposed one of the most severe lockdowns, closing all non-essential businesses, schools and daycare centers, and limiting private social gatherings to just two visitors per household per day until at least mid-January.

In Denmark, cultural venues have closed and strict vaccine and mask mandates are in place at restaurants, cafes and bars, also being forced to stop serving alcohol after 10 p.m. and to close between 11 p.m. and 5 a.m.  

The United States, meanwhile, was averaging 267,000 COVID cases a day over the past week, a record high, which experts attributed to twin attacks of the Delta and Omicron variant.  That, in turn, led to a domino effect of other measures, including delays in reopening dates for some universities in the new year, flight cancellations and absences of transit, travel and health workers. 

The consequent labour disruptions  led the US Centers for Disease Control on Monday to shorten its recommended isolation period for an infected individual from 10 days to just five – a measure that immediately sparked debate among experts over whether that would indeed propel infections even more.   

Boosters – WHO messages out of step with countries 

WHO Chief Scientist Dr Soumya Swaminathan, at WHO end-year press conference marking two-years since the first reports of the novel coronavirus circulating in Wuhan, China were picked up by WHO.

To counter the wave of infections, national leaders like the UK’s Prime Minister Boris Johnson on Wednesday were urging everyone to get boosted as soon as possible, noting that 90% of cases in ICU lacked their third jab – while the National Health Services wished the public a “jabby New Year”, highlighting a recent study on how most of people critically ill with COVID lack booster status. 

WHO, however, continues to sound a different tune. 

At Wednesday’s press conference, Tedros and WHO Chief Scientist Dr Soumya Swaminathan insisted once more that two shots are enough for most healthy people – while third boosters should be reserved only for those at highest risk. 

The bigger focus for rich countries, said Tedros, should be on reaching people who are unvaccinated altogether as they are still the people most likely to have severe disease. 

“That would have a better impact and also help us make progress toward ending the acute phase of the pandemic,” he said. 

He admitted, however, that WHO’s opposition to universal booster jabs also is deeply rooted in fears that even with vaccine supplies expanding, booster campaigns could  divert badly needed vaccines from the nearly 100 low- and middle-income countries that have yet to vaccine even 40% of their populations – as compared to the 60- 70% coverage seen in most high-income countries.   

More new variants could be “fully resistant” to existing measures, WHO head warns 

And that, WHO has warned, could lead to the emergence of still other new variants among the unvaccinated in developing regions -which could in turn prolong the duration of the pandemic for the world. 

“There’s even talk of fourth doses in some countries,” said Swaminathan, in an  obvious reference to an Israeli debate now raging over the pros and cons of yet another mRNA Pfizer booster. 

Rather than blanket boosters, “it is particularly important to vaccinate frontline workers, the elderly & elderly in all countries, and not just a few.” she underlined. 

“Vaccine supply, for now at least, is improving although the emphasis on boosters in rich countries could cause low income countries to go short,” said Tedros, adding that “Again. I call on leaders of rich countries and manufacturers to learn the lessons of Alpha, Beta Gamma Delta and now Omicron and work together to reach 70% vaccination coverage [worldwide]. 

“This is the time to rise above short-term nationalism and protect populations and economies against future variants by ending global vaccine inequity.

“Ending health inequity remains the key to ending the pandemic. And as this pandemic drags on. It’s possible that new variants could evade our countermeasures and become fully resistant.” 

Image Credits: Gauteng Department of Health.

Drs. Maria Elena Bottazzi and Peter Hotez, CORBEVAX™ lead developers at Baylor College of Medicine’s Center for Vaccine Development. 

Vaccine equity advocates see huge potential in India’s decision to grant an emergency use license to CORBEVAX™, an open-license vaccine dubbed “The World’s COVID-19 Vaccine” by its developers at Texas Children’s Hospital and Baylor College of Medicine.

The protein sub-unit vaccine, engineered at Baylor’s Center for Vaccine Development (CVD), received the Emergency Use Authorization (EUA) approval on Tuesday from the Drugs Controller General of India (DCGI). Plans are to first launch the vaccine in India and “other underserved countries to follow.”

The vaccine production in India has been licensed to the Hyderabad-based vaccine and pharmaceutical company Biological E. Limited (BE), said the developers in a press release Tuesday. 

“We technology transferred our vaccine and helped in its co-development with BioE with NO PATENT and no strings attached.  As a result it should be the least expensive COVID vaccine available yet,” said the vaccine’s lead co-developer, Dr. Peter Hotez, in a tweet just after the news was announced.

“BioE now has 150 million doses ready now, and will be making 100 million per month,” Hotez added. “In so doing our Texas Children’s has just matched or doubled the US Government current commitment to global vaccine equity.”

Hotez, dean of Baylor’s National School of Tropical Medicine at Baylor and co-director of the Center for Vaccine Development, is a well-known US vaccine expert who has become a popular US news commentator during the pandemic. The R&D team was co-led by Dr. Maria Elena Bottazzi,  Associate Dean of the National School of Tropical Medicine at Baylor and co-director of the Center for Vaccine Development. 

Not patented – vaccine aims to serve underserved regions

Laboratory staff at the Center for Vaccine Development

More significantly, as the vaccine is not patented, the developers have declared that they hope to replicate more non-exclusive licenses for the vaccine know-how and production process in other under-served regions of the world. 

The vaccine uses traditional recombinant protein-based technology – wielding a selected protein subunit from the SARS-CoV2 pathogen to provoke immunity. That is as compared to mRNA vaccines that prompt immunity using a only a strand of the pathogen’s RNA code.  The protein-based vaccine production process that is already familiar to drug manufacturers the world over.  That, says its developers, should allow for rapid scale-up in other low- and middle-income countries. 

“This announcement is an important first step in vaccinating the world and halting the pandemic. Our vaccine technology offers a path to address an unfolding humanitarian crisis, namely the vulnerability the low- and middle-income countries face against the delta variant,” said Hotez in the press release. 

“Widespread and global vaccination with our Texas Children’s-Baylor-BE vaccine would also forestall the emergence of new variants. We have previously missed that opportunity for the alpha and delta variant. Now is our chance to prevent a new global wave from what might follow.”

“Protein-based vaccines have been widely used to prevent many other diseases, have proven safety records, and use economies of scale to achieve low-cost scalability across the world,” said Bottazzi. 

“Our decade-long studies advancing coronavirus vaccine prototypes has led to the creation of this vaccine, which will fill the access gap created by the more expensive, newer vaccine technologies and that today are still not able to be quickly scaled for global production.”

Superior response to COVISHIELD & fewer adverse effects

The press statement said that CORBEVAX™, after completing two Phase III clinical trials involving more than 3000 subjects, was found to be safe, well tolerated and immunogenic.

It also said that CORBEVAX™ demonstrated “superior” immune response in comparison to the Astra-Zeneca COVISHIELD™ vaccine, produced by the Serum Institute of India – with fewer adverse effects, saying:

“ CORBEVAX™ demonstrated superior immune response in comparison with COVISHIELD™ vaccine when assessed for Neutralizing Antibody (nAb) Geometric Mean Titers (GMT) against the Ancestral-Wuhan strain and the globally dominant Delta variant. CORBEVAX™ vaccination also generated significant Th1 skewed cellular immune response.

“While none of the subjects who took CORBEVAX™ or COVISHIELD™ had serious adverse events, CORBEVAX™ had 50 percent fewer adverse events than COVISHIELD™,” the vaccine’s developers also stated.

In other efficacy members, the developers said:  

  • CORBEVAX™ nAb GMT against Ancestral-Wuhan strain is indicative of vaccine effectiveness of >90% for prevention of symptomatic infections based on the Correlates of Protection assessment performed during Moderna and Astra-Zeneca vaccine Phase III studies.
     
  • CORBEVAX™ nAb GMT against the Delta strain indicates a vaccine effectiveness of >80 percent for the prevention of symptomatic infections based on published studies.

“Over the years, we have worked to make quality vaccines and pharmaceutical products accessible to families around the world. With this as our backdrop, we resolved to develop an affordable and effective COVID-19 vaccine. It has now become a reality,” said Mahima Datla, Managing Director, Biological E. Limited, which is also receiving support from the Oslo-based Coalition for Epidemic Preparedness (CEPI), and Bill and Melinda Gates Foundation. 

“We deeply appreciate Texas Children’s Hospital Center for Vaccine Development, Baylor, CEPI, the Bill and Melinda Gates Foundation, and the government of India for their continuous support and cooperation during this journey. The combined efforts & unceasing support demonstrate that we can collectively overcome any challenge”. 

Given its reliance on more traditional vaccine technology, the vaccine may be  potentially more acceptable to some groups than cutting edge mRNA vaccines, observers also said.

Similar technology to Hepatitis B Vaccine and other common vaccines

Reportedly, the vaccine’s developers are now also conducting talks with WHO’s C-TAP vaccine pool about formalizing their patent-free model for sharing the vaccine technology. If a deal was signed, they would be the first vaccine to join the pool – which has so far failed to pick up support from other major vaccine innovators worldwide.

“We’re really excited about this,” said  Jamie Love, of Knowledge Ecology International.  While the vaccine itself is not under patent, the Baylor team aims to license their know-how and access to cell lines widely to LMIC pharma firms, providing a good practice example of technology transfer that few others have followed. “They have worked in manufacturers in Indonesia, Bangladesh and Brazil, and are talking with others too.”    

CORBEVAX™ is the third protein subunit vaccine to enter the market.  Others include a vaccine developed by Cuban researchers and Covovax, the India-produced version of the vaccine developed by the US firm Novavax, which received WHO emergency use approval on 17 December, followed later by a European Medicines Agency authorization for the European version of the vaccine.

“The vaccines are safe, and may appeal to those who don’t want the mRNA vaccines, who may accept a more traditional vaccine platform,” Love said, adding, “also, they may play a role as a booster, which is where the market is headed,” adding, “I think the protein subunit vaccines from places like Baylor – and Cuba – are really not talked about enough.

“Messenger RNA is a really good initial thing, but I don’t know how durable they are or how they will look going forward. The mRNA vaccines [Pfizer and Modern] are keeping people out of hospitals and from dying, but they are not stopping Omicron. 

“And if you look at other vaccines, the Chinese or Russian vaccines, they still have played a pretty good role in keeping people out of the hospital and dying. You now have three protein subunit vaccines out there; they look like they are important. One thing we will want to look at is just how durable they are in terms of protection, in comparison to the messenger RNA, and see how they perform.” 

But either way the vaccine dice finally rolls: “having multiple vaccine candidates is always positive.”  

For more about the four key types of COVID vaccines, see this video:

https://youtu.be/lFjIVIIcCvc

Image Credits: Texas Children's University , Texas Children's Hospital.

COVID19 Moonshot: (Molecular) view of a key component of the SARS-CoV-2 virus called MPro (green-grey) with potential drug site targets identified in yellow.

A global grassroots movement of scientists based on crowdsourcing ideas, expertise, and goodwill has already generated – and freely released – more than half of the known structural information on the main protease of SARS-CoV-2. Based on this, they are now on a quest for an open-source drug that can block the virus from replicating.

Antiviral pills to treat SARS-CoV-2 infection are finally starting to arrive. This week’s announcement of the US Food and Drug Administration’s approval of the first two oral antivirals for COVID-19, including Merck’s molnupiravir, and Pfizer’s Paxlovid™, has stirred much attention for the potential of the new treatments to significantly reduce risks of serious COVID disease through therapies available at point-of-care.  

There are more in the pipeline.

The rapid spread of new variants such as Omicron underlines the importance of antiviral pills that can reduce the risk of progression to severe disease and help prevent hospitalization and death. In the context of deeply unequal global vaccine distribution and waning immunity, the need is more critical than ever. This is particularly true in places with limited intensive care capacity.

Will long awaited antivirals be easily accessible?

But will these long-awaited antivirals be easily accessible to everyone who needs them, especially in low- and middle-income countries (LMICs)?

If distribution of COVID-19 vaccines is an indicator, it does not bode well for broad access to new drugs. High-income countries have distributed more booster jabs in the last three months than low-income countries (LICs) have injected initial doses in the last year, the Financial Times noted in November. To date, only 7% of people in LICs have received at least one shot.

Without action, the gross inequity seen in vaccine distribution is on course to be repeated with therapeutics.

Despite some licensing agreements to improve access in several LMICs, there are concerns that production and supply will be limited. Furthermore, many middle-income countries are excluded from these agreements. This means they will face high prices and be pushed to the back of the queue as – once again – rich countries seek to stockpile supplies in advance.

‘Ragtag’ group of researchers make a moonshot 

Part of the solution could come from a ‘ragtag’ group of researchers from around the world who are working to develop a straight-to-generic COVID-19 antiviral from scratch. The goal is a new, safe, orally active, affordable, simple-to-administer drug – one that would be immediately and globally accessible, especially in limited-resource settings.

This open-science drug discovery initiative is called The COVID Moonshot.

It all started with a Tweet…..

The Moonshot, involving scientists around the world and a high-throughput platforms for drug discovery.  The initiative began with a tweet from the Weizmann Institute of Science.  Diamond Light Source, a UK-based research institute at the Harwell Science and Innovation Campus in Oxfordshire is also a key partner.

It all started with a tweet. In March 2020, a medicinal chemist at Israel’s Weizmann Institute of Science computational and chemical biology lab tweeted a call to peers to submit designs of molecules that would be able to block the main protease of SARS-CoV-2. 

As the world was entering into lockdown, hundreds of scientists and students put their own projects on pause, and spontaneously started to make designs around the initial kernels of the ideas coming from the COVID Moonshot: a rich experimental dataset of small design building blocks bound to the active site of the main protease of the SARS-CoV-2 virus.

In a matter of months, more than 50,000 crowdsourced design ideas for drugs and molecules were submitted and 1,400 of them were made and tested. ‘Open drug discovery efforts are invariably super slow – ours has been an express train on tracks we have had to lay down as we go,’ wrote the researchers. Multiple promising compounds have since been identified; the best will progress through preclinical evaluation in the coming months. 

This grassroots movement based on crowdsourcing ideas, expertise, and goodwill has already generated – and freely released – more than half of the known structural information on the main protease of SARS-CoV-2.

A drug that can block the protease “scissors” could stop the virus from replicating

COVID19-Moonshot – Crystal samples of SARS-CoV-2 free enzyme

A quick scientific note here: the protease is a viral enzyme which acts like scissors cutting up the very long polyprotein which is produced by the cell infected by the SARS-CoV-2 virus, releasing the machinery that the virus needs to multiply itself. A drug that can block these ‘scissors’ by inserting itself into a specific site of the protease could stop the virus replicating.

In September, our crowdsourced, open-science initiative received £8 million in key funding from the UK-based charitable foundation Wellcome, to prepare its most promising compounds for clinical trials. We aim to declare three pre-clinical candidates by March 2022, for which preclinical safety and toxicology testing and the required chemistry, manufacturing and control (CMC) steps will be performed by several expert contract research organizations. Based on this data, we will choose the most promising compound and develop it for Phase-1 readiness by June 2023.

The COVID Moonshot works closely with a dedicated team from the Drugs for Neglected Diseases initiative (DNDi), a not-for-profit drug development organization,  to ensure efficient decision-making during preclinical development, and identify a feasible clinical and downstream development strategy.

Drug discovery usually goes on behind closed doors – Moonshot researchers are charting an open-science course

COVID19 Moonshot: high tech experiments at the UK’s Diamond Light Source, at the Harwell Science and Innovation Campus in Oxfordshire, UK

Drug discovery is usually conducted behind closed doors, its secrets tightly guarded. But Moonshot researchers believe that open science may lead to a better, more equitable way of combatting COVID and future pandemics. We believe that the traditional economic model of pharmaceutical development does not meet the needs of all patients in the context of pandemics and that open-science drug discovery can significantly contribute to public good.

As such, Moonshot includes the fully open sharing of results – including negative ones – with no research ‘secrets’ locked away and no restrictions on their use. Our results will eventually be published through full peer-review. In the meanwhile, the design structure and data generated thus far are freely available on the Moonshot website.

Until recently, the only treatments available for patients with early stage COVID-19 were monoclonal antibodies, which require intravenous infusion and hospitalization, and are expensive and difficult to implement in resource-limited settings. In contrast, future Moonshot antivirals should come in the form of simple pills. Ideally, they will be safe and simple enough to be easily prescribed and accessed via pharmacies. While others are also developing oral-use antivirals, the difference with Moonshot is its model, which ensures that intellectual property will not prevent affordable and global access.

There may be opportunities to combine Moonshot antivirals with other drugs 

There may also be the opportunity to combine Moonshot antivirals with the other COVID antivirals or other drugs to boost their impact. As seen with other viral diseases such as HIV and hepatitis C, combining different drugs is more effective, helping to defend against new variants and prevent resistance from mutations. The more efficient combinations of antivirals against COVID, the better.

Ultimately, solutions to the COVID-19 pandemic, and future pandemics, cannot only come from scientific breakthrough, remarkable as it has been. The way in which the global community chooses to implement these are just as critical to its success. A pill is no good to a patient who can’t access it. As researchers, we believe that every person on this planet, without exception, should have access to the life-saving innovation offered by the best science, as soon as they become available.

The enthusiastic response to Moonshot from scientists from all over the world is highly encouraging.  We will continue to work hard to make this commitment a reality, in the form of a simple pill, affordable and available to all.

Dr Annette von Delft is a translational scientist at the Centre for Medicines Discovery, University of Oxford.

Dr Charles Mowbray, is director of discovery at the Drugs for Neglected Diseases initiative (DNDi).

Dr Borna Nyaoke, is the senior clinical project manager at DNDi in charge of the ANTICOV clinical trial in Kenya.

Image Credits: © Diamond Light Source, 2021, DNDi, Diamond Light Source, 2021, DNDi .

A major new British study has provided encouraging data that people infected with the Omicron variant are 20% less like to visit a hospital and 40% less likely to be admitted overnight than those with the Delta variant.

The Imperial College study, published Thursday, looked at everyone with a confirmed infection of either variant in the UK between 1-14 December – for a total of more than 324,000 cases.   

At the beginning of the tracking the 164 Omicron cases detected comprised only .6% of total daily cases recorded  By day 14, however, there were 15,804 Omicron cases –  more than 50% of the nearly 30,000 cases a day being reported – reflecting the steep rise in infections from the new variant.  

“Overall, we find evidence of a reduction in the risk of hospitalisation for Omicron relative to Delta infections, averaging over all cases in the study period,” concludes the study, undertaken by researchers at Imperial College. 

“The extent of reduction is sensitive to the inclusion criteria used for cases and hospitalisation, being in the range 20-25% when using any attendance at hospital as the endpoint, and 40-45% when using hospitalisation lasting 1 day or longer or hospitalisations with the ECDS discharge field recorded as “admitted” as the endpoint.

However, the proportionately smaller rate of hospitalizations must be balanced against the “the larger risk of infection with Omicron, due to the reduction in protection provided by both vaccination and natural infection,” the researchers warned.  

Imperial College, UK, study reveals 40% lower hospital admissions for Omicron cases as compared to Delta, even as Omicron rapidly becomes the dominant SARSCoV-2 variant.

Hospitalization risks for people vaccinated and previously infected

The study also found that previous COVID infection reduced the risk of any hospitalisation by approximately 50% and the risk of a hospital stay of 1+ days by 61%.

Cases vaccinated with Pfizer or Moderna for doses 1 and 2 have a similar or higher risk of hospitalisation with Omicron compared with Delta, while cases vaccinated with AstraZeneca for their primary series tended to have a lower risk of hospitalisation relative to Delta. 

The studies authors noted that the small overall numbers of people hospitalized with Omicron so far limits their ability to interpret the data – in light of vaccination status. 

“As more data accumulate, with longer periods of follow-up, assessment of more severe outcomes will become feasible,” report the study’s authors, who are part of the Imperial College COVID response team, and also a WHO Collaborating Center. 

“Currently, vaccination-status stratified hazard ratio estimates … remain very sensitive to small numbers of hospitalisation, particularly in the unvaccinated Omicron group. 

“It is quite possible that larger reductions in hospitalisation risk for Omicron vs Delta may be estimated [among  those vaccinated] for the endpoints of ICU admission and death, given that remaining immune protection against more severe outcomes of infection are expected to be much higher than those against milder endpoints.”

Image Credits: PAHO.org, Imperial College, UK.

USFDA Approval of Merck’s Monulparivir Thursday follows upon the FDA;s approval of Pfizer’s Paxlovid Wednesday – which many scientists see as the preferred SARS-CoV2 oral drug.

WASHINGTON D.C. (ENDPOINTS News) – The FDA on Thursday authorized another new pill to treat the Omicron variant, this time from Merck.

The FDA decision follows upon a decision Wednesday authorizing Pfizer’s Paxlovid oral treatment, which the company said had proved to reduce the relative risk of hospitalization or death by 89% (within three days of symptom onset) and 88% (within five days of symptom onset) compared to placebo in a trial of more than 2,000 people.

Merck’s pill, monulpiravir, saw its efficacy plummet between interim and final analyses in its pivotal trial — from a 50% relative reduction in hospitalizations and deaths at the interim to just 30% in the final results — meaning that more doctors will likely rely on the Pfizer pill. There are also questions about how Merck’s pill works, which led France’s experts to reject it.

While Pfizer’s antiviral may prove to be more effective, and Merck’s pill has left some scientists questioning the dangers behind its mechanism of action, molnupiravir will be another weapon in the armamentarium of Covid-19 treatments for the US in a time of need, as two mAb treatments from Regeneron and Eli Lilly are no longer effective against Omicron, and as supplies of a third mAb from Vir/GlaxoSmithKline are very limited.

Merck has also reached a deal for the worldwide distribution of monulpiravir at reduced prices, through the Medicines Patent Pool, while Pfizer has said it will offer it’s pill to low- and middle-income countries at reduced prices.

Pfizer Says New Anti-Viral Drug Combination Cuts Risks Of Serious COVID-19 By 89% 

Supplies of Merck pill more immediately available

In the US, as well, supplies of the Merck pill will not be as limited, as the US may have about 400,000 courses of Merck’s pill available in the next few days, and by the end of January, the US government expects to have about 3 million courses of Merck’s pill, which is the entire order that the US made.

The concern with Merck’s pill is that it works by inhibiting SARS-CoV-2 replication through viral mutagenesis, and some scientists have raised serious reservations about that MOA.

The FDA’s Antimicrobial Drugs Advisory Committee narrowly voted 13-10 last month in favor of the pill’s benefits outweighing the risks for adults within 5 days of developing Covid symptoms.

“Committee members who voted ‘No’ cited the following as reasons for concluding that the overall benefit-risk ratio was unfavorable: 1) a high number-needed-to-treat compared with placebo, 2) unclear efficacy against the Delta variant, 3) potential to drive viral mutations, and 4) mutagenicity risks,” according to a summary of the meeting.

Merck has to provide reports to the FDA on a monthly basis summarizing any findings as a result of its monitoring activities of genomic database(s) for the emergence of global viral variants.

As part of Thursday’s authorization, FDA made clear that it should be provided to those “for whom alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate,” meaning that if Pfizer’s pill is available, that might be a better option.

Scientists still see wider preference for Pfizer pill

“I don’t think you would find anyone who would prefer the Merck pill to the Pfizer pill, given the data evident so far,” Walid Gellad, a professor of medicine at the University of Pittsburgh, told Endpoints News previously.

As part of the EUA, the FDA said Merck has to “conduct a thorough investigation into the differences in efficacy observed in the first and second half” of its pivotal trial. Panelists at the adcomm last month centered their questioning on the cause of this drop-off in preventing hospitalizations and deaths, from 50% to 30% between interim and final results. Merck and the FDA offered few specifics at the meeting on why the efficacy declined.

Unlike the Pfizer pill, the FDA also warned Thursday that molnupiravir is not recommended for use during pregnancy, as based on findings from animal reproduction studies, molnupiravir may cause fetal harm.

Merck must maintain a pregnancy surveillance program to collect information on individuals who are exposed to molnupiravir during pregnancy. FDA also said that sexually active individuals with partners of childbearing potential are advised to use contraception during molnupiravir treatment and for at least three months after the last dose.

Molnupiravir is also not authorized for use in patients who are less than 18 years of age, or for use for longer than 5 consecutive days. A course of treatment is administered as four 200 milligram capsules taken orally every 12 hours for five days, for a total of 40 capsules.

Reprinted with permission from ENDPOINTS News: FDA Authorizes New Merck COVID-19 Pill & FDA authorizes the first at-home pills from Pfrizer to treat COVID-19.  @ZacharyBrennan is a senior editor covering the FDA and regulatory policy.

Image Credits: Pfizer .

Hard-hit by Omicron, South Africa has launched a mass COVID vaccination booster campaign, as well as a drive to vaccinate adolescents age 12-17. WHO continues to recommend against both moves.

WHO has issued new advice to countries supporting booster campaigns for “high risk groups” but still opposing “blanket” campaigns – or vaccines for children and adolescents under the age of 18.

The latter, top WHO officials contend, could divert too many vaccines from low-and-middle member states that have low vaccination coverage rates – leading to a boomerang of new variants that also prolong the pandemic.

The WHO advice is being widely ignored, however, as 120 countries worldwide are already vaccinating boostering adult populations in order to ward off yet a new wave of the SARS-CoV2 virus, increasingly driven by the Omicron variant.  Among those are South Africa, at Omicron’s epicenter, which earlier this month began offering boosters to anyone already jabbed with two Pfizer shots – as well as second vaccines to teens aged 12-17. On Wednesday, however, South African health officials said they were seeing a drop-off in soaring infection rates – while fewer cases were ending up hospitalised than would have been the case for the previous Delta wave.  

In terms of boosters guidance, the new recommendations by WHO’s SAGE experts paint a very broad brush – recommending that countries  introduce booster campaigns that are “evidence driven and targeted to the population groups at highest risk of serious disease and those necessary to protect the health system”.

While cautious, and still seemingly out of step with what is happening on the ground, the new WHO advice that countries might consider boosters for “high-risk” groups – walks back from Director General Dr Tedros Adhanom Ghebreyesus’ previous calls for a booster “moratorium” – excepting immunocompromised people, such as cancer patients. 

WHO Director General Dr Tedros Adhanom Ghebreyesus

The SAGE statement avoids any specific recommendations about what ‘high-risk’ groups might actually be the best booster candidates – leaving countries to decide if they want to prioritise people at occupational risk, such as health workers, older people and/or those with chronic diseases.  

Speaking at a Wednesday’s pre-holiday press briefing, Dr Tedros conceded that boosters could indeed be selectively administered to unspecified “high risk” groups without jeapordizing global supplies – but stressed that broad-based booster campaigns should still be avoided.  

“Our projections show that supplies should be sufficient to vaccinate the entire global adult population and to give boosters to high risk populations by the first quarter of 2022,” he said. 

“However, only later in 2022 will supply be sufficient for extensive use of boosters in all adults. So I call once again on countries and manufacturers to prioritize COVAX and work together to support those who are furthest behind.”  

He failed to elaborate.

No details on WHO vaccine supply projections

Despite repeated requests by Health Policy Watch, WHO has not provided further details of its vaccine supply and demand projections under different booster scenarios.

Last week, however, a senior WHO official predicted that low-income countries could come up 3 billion doses short in the first quarter of 2022 if boosters were “aggressively” administered in the some 120 high- and middle-income countries that have begun offering third jabs – a statement later challenged by the pharma industry.

The WHO projection assumed that the high-and middle income countries that have launched booster campaigns would reach 90% coverage with primary vaccines and boosters by March 2022 – when in fact coverage in most countries has failed to reach even 70% for just the primary vaccine series.

Financial Times mapping of WHO claims of 3 billion vaccine dose shortfall – based on 90% vaccine coverage in all high/upper middle income countries.

Acknowledges waning immunity for the first time 

Soumya Swaminathan, WHO Chief Scientist

The new SAGE advice also acknowledges, for the first time, evidence of waning immunity against SARS-CoV2 over time, conceding that there is a :”decline in vaccine effectiveness against SARS-CoV2 infection and COVID-19 with time since vaccination, and more significant decline in older adults.“

That evidence includes an 8-15% decline in protection against serious COVID disease among all age groups, and a 32% decline in protection against symptomatic disease for people over the age of 50 – from the leading mRNA and AstraZeneca vaccines, according to the WHO expert review.  

The policy statement also acknowledges that the erosion of vaccine-derived immunity might be even more pronounced in the case of the Omicron variant. 

Vacccine efficacy against Omicron – still many uknowns

Speaking at the press briefing, WHO Chief Scientist stressed that there remain many unknowns about vaccine efficacy against the new variant – most knowledge is based upon laboratory assays – not real-life experience.

“Almost all of the lab assays have shown a considerable reduction of neutralization [antibody capacity] against the Omicron variant. But there should still be a good amount of T-Cell immunity,” she added, noting that immunity is grounded in multiple pathways.”

“For now we believe that boosters may be needed for people who have weaker immune systems, older individuals more vulnerable people,” Swaminathan said in a video released shortly before the presser.  

The SAGE experts also point out that administration of booster doses to the more vulnerable might be preferable to the administration of primary doses to low-risk groups – particularly children and adolescents – which WHO still has not recommended be vaccinated at all: 

“Modeling shows that greater reductions in mortality may be achieved by administering booster doses to high-risk populations than using those same doses for primary immunization of lower risk populations. 

“As supply increases and vaccination is expanded to lower priority age groups, trade-offs may need to be considered as to prioritizing booster vaccination to high-risk populations over expanding primary immunization coverage to younger populations. WHO is currently not recommending the general vaccination of children and adolescents as the burden of severe disease in these age groups is low and high coverage has not yet been achieved in all countries among those groups who are at highest risk of severe disease,” the SAGE group concluded. 

Global equity and supply 

COVAX supply forecasts – from a vaccine facility for the world, it has become a vaccine supplier largely to the world’s 93 lowest-income countries, including large quantities of donated doses – with huge lags in delivery dates.

A key consideration in the booster recommendations continues to be fears that global vaccine supplies could be diverted from the global COVAX vaccine facility and African Union efforts, which are trying to ensure that vaccine coverage reaches the 40% target in the more than 90 low-income WHO member states that have struggled to roll out vaccines altogether.  

“Only half of WHO member states have been able to reach the target of vaccinating 40% of their populations by the end of the year, because of the distortions in the global supply,” said Dr Tedros in his media comments, adding that: 

“Enough vaccines were administered globally this year that the 40% target could have been reached in every country by September. If those vaccines had been distributed equitably, through COVAX  and others. 

“We are encouraged that supply is improving. Today, COVAX shipped its 800 millionth vaccine dose –  half of those have been shipped in the past three months. 

For national health systems, “the focus of immunization must remain on decreasing deaths and severe disease.” 

Blanket booster programmes likely to prolong the pandemic, rather than ending it

But countries have another good reason to be selective about booster jabs, Tedros added, saying that: “Blanket booster programs are likely to prolong the pandemic rather than ending it.

“Diverting supply to countries that already have high levels of vaccination coverage, gives the virus the opportunity to spread and mutate,” he added. 

 “It’s important to remember that the vast majority of hospitalizations and this are in unvaccinated people, not unboosted. 

“The global priority must be to support all countries to reach the 40% target as quickly as possible. And the 70% target by the middle of this next year [2022]. No country can lose its way out of the pandemic.”

Use N-95 Masks – new  WHO advice to health workers in light of Omicron concerns 

A USA FDA certified brand of N95 particulate respirator mask for health workers; the highest quality ones are rated by national authorities but cheaper imitations from Asia have also flooded markets since the beginning of the COVID pandemic.

In a parallel announcement, WHO also said it is recommending that health workers routinely use more protective N-95 or FFP-2 respirator masks with a rated ability to filter out most fine particles – including virus-bearing aerosols. 

The masks, along with gowns, gloves and eye protection, should be worn by any health care workers entering any room where suspected or confirmed COVID patients might be lodged.  

The recommendation was accompanied by a call from Dr Tedros to mask manufacturers to step up their production of the masks saying: 

“We are painfully aware that many health workers around the world are unable to access respirators. We therefore ask manufacturers and countries to scale up the production procurement and distribution,” he said. 

In light of respirator [mask] shortages and burgeoning mask waste disposal issues, he noted that WHO also has issued an initial summary of evidence around methods for reprocessing the higher-quality N-95 respirator masks or their equivalent  – including UV light exposure, heat exposure, sterilization, and chemical treatment, e.g. with hydrogen peroxide vapours.

Omicron is clearly more transmissible, but is it as severe as Delta? 

Maria Van Kerhkove, COVID-19 Technical Lead

The recommendations come as certainty mounts that the  Omicron variant of SARS-CoV2  is more transmissible than its Alpa, Beta, Gamma or Delta predecessors – although it’s too soon to conclude if the variant is less or as severe as Delta, which swept the world in spring 2021.

“What we are learning about Omicron is certainly that we have this increased transmission, but the information on severity is still uncertain,” said Maria Van Kerkhove, WHO COVID technical lead on the Health Emergencies team. 

“We don’t have that complete picture yet it is too early to conclude whether or not Omicron is less severe than Delta or is as severe. 

“Now we do have some data suggesting that rates of hospitalization are lower, that people who are hospitalized don’t need as much oxygen or invasive ventilation. 

“But again, we have not seen this variant circulate for long enough in populations around the world, certainly in vulnerable populations. We did learn some information this week that older people with Omicron tend to have more severe disease. That’s unsurprising. 

“We know people have died from Omicron… but the data is a little bit messy, it’s being generated right now,” she added, concluding with a plea that groups celebrating the Christmas and New Years holidays curb their social contacts in order to cut down on the variants’ rapid advance across the globe.  

“We have been asking people to be cautious. We’ve been asking governments to be caution and to really think, especially as these holidays are coming up, and there are very difficult decisions that need to be made in terms of making sure that we keep ourselves safe.”

Image Credits: Gauteng Department of Health, The Financial Times , Airfinity, ACS Material/BYD Brand .

Exclusive end year WHO media briefing in Geneva behind closed doors on Monday

Driven by Omicron, Africa is facing a steep wave of new COVID infections – last week reporting the fourth highest number of cases ever recorded in a single week, said WHO Director General Dr Tedros Adhanom Ghebreyesus on Monday. 

He was speaking at an exclusive media briefing in Geneva behind closed doors to a handful of international media outlets with UN-accredited Geneva bureaus.

The rambling two-hour long briefing, released a day later on YouTube, excluded Geneva-based health media as well as most African, Asian, and Latin American media across the world – which the UN press office in Geneva does not recognise or credential. 

While some reporters linked up online, the in-person gathering with reporters hosted by the UN Office at Geneva occurred at a time when Switzerland is facing one of the highest infection rates in the world – and other mass gatherings in Switzerland, such as the World Economic Forum’s 2022 meeting in Davos, have recently been cancelled. 

“Africa is now facing a steep wave of infections, driven largely by the Omicron variant,” said the Director General in the briefing, shared only a day later with Geneva health media, as well as other national and regional media worldwide.  

“Just a month ago, Africa was reporting its lowest number of cases in 18 months. Last week, it reported the fourth-highest number of cases in a single week so far,” he said. In fact, while Africa’s rates remain low overall, due to what experts attribute to a complex range of factors include a younger population and widespread underreporting, new infection rates in southern countries like Botswana, Eswatini and South Africa have now soared to worrisome highs. Per capita reported new infections in those states, where Omicron was first discovered, are comparable to those in the most infection-wracked countries of Europe, including Switzerland and Germany. 

“There is now consistent evidence that Omicron is spreading significantly faster than the Delta variant,” said the DG, in a wide-ranging briefing with senior staff, which looked at the pace of Omicron spread, booster campaigns, and new vaccines under review or approval – as well as reviewing WHO’s record for the year 2021.

Given the fast pace of Omicron’s spread, the WHO Director General urged people preparing for the upcoming Christmas and New Years’ holidays to cancel or delay mass events and social gatherings, in order to slow the variant’s advance. 

“All of us are sick of this pandemic. All of us want to spend time with friends and family. All of us want to get back to normal,” the Director-General declared.  

Dr Tedros Adhanom Ghebreyesus, WHO Director General

But given Omicron’s unique ability to avoid previously acquired immunity, “it is more likely that people who have been vaccinated or have recovered from COVID-19 could be infected or reinfected,” he added. 

And faced with that reality, “there can be no doubt that increased social mixing over the holiday period in many countries will lead to increased cases, overwhelmed health systems and more deaths.  

“The fastest way to do that is for all of us – leaders and individuals – to make the difficult decisions that must be made to protect ourselves and others. 

“In some cases, that will mean canceling or delaying events – just as we have had to cancel the reception we planned to have with you today,” he said, referring to a social event that had been planned for the journalists who had gathered physically at WHO headquarters, following Monday’s briefing.  

“But an event canceled is better than a life canceled. It’s better to cancel now and celebrate later, than to celebrate now and grieve later,” he added.  

Walking back on opposition to boosters 

Senior WHO Advisor, Dr Bruce Aylward

The Director General, as well as senior members of his team, also walked back some of their previous messaging opposing booster vaccines- admitting that there is growing evidence about their potential medical value – particularly for older people.  

“Clearly there is increasing evidence that those most vulnerable will benefit from an additional dose.  Yes, there is a role, but we want to ensure the right programme and vaccinate in the right order,” said Dr Bruce Aylward, WHO senior advisor. 

Aylward and other senior staff stressed that WHO remained opposed to mass booster campaigns on equity grounds – due to fears this will divert potential doses needed by  the more than 90 low-income countries which will miss the 40% vaccination coverage target set by WHO for the end of this year.  

“Remember what we are seeing in some places is not just a booster for those at highest risk but a booster for everyone in the population,” said Aylward. 

“And again, that would make a real demand on vaccines in an environment where they simply are not available to everyone who needs them at this time.”

However, Aylward later contradicted himself somewhat saying that in the first quarter of 2022:  “there will be enough vaccines to vaccinate 40% of the population of every country in the world, plus give a third dose to everybody over 50 years old. So we are very quickly getting into a situation where the production capacity is sufficient.

“The challenge is making sure the right products get  to the right places,.. optimising the allocations to get to where its needed .. to these countries that have been starved of vaccines for so long. everyone in high-income countries over the age of 50 as well as to distribute sufficient doses in low-income countries to meet the WHO 40% goals.”

Added Tedros, “There is new evidence emerging now of the benefits for elderly, over 65, so if it [booster] is going to be used, it’s better focusing on those groups. 

“But some countries are doing boosters very aggressively while their hospitals are filled with people who are not vaccinated. 

So the best would be for countries to convince those who are not vaccinated, convince them to be vaccinated and make sure that they are safe.  Their energy should be spent on finding the unprotected and protecting them.” 

He added: “Instead of boostering a child in high income countries, it’s better to vaccinate the elderly in counties who have not been vaccinated even with the primary vaccines. So the equity issue will also come into play.”  

Data on boosters’ impacts on global supplies lacks transparency

So far, WHO has not come up with detailed data around the likely impact of booster campaigns on global supplies for low- and middle-income countries – despite repeated requests by Health Policy Watch for more clarification of the data and its statements.  

An interview with one senior WHO official, published last week in the Financial Times, claimed that mass boosters in higher income countries could leave global supply chains 3 billion doses short of what is needed for developing regions in the first quarter of 2022.   

But those estimates are based on a presumption that 90% of people in high income countries would accept boosters – when in fact not even 70% have received their first and second jabs. 

Financial Times mapping of WHO claims of 3 billion vaccine dose shortfall in “aggressive scenario” – assumes 90% vaccine coverage in high- and upper-middle income countries.

Conversely, in a pharma-sponsored briefing last week, the data forecasting firm Airfinity claimed that boostering 70% of the population in G-7 countries would not significantly dent supplies needed by LMICs – since the world is now producing over 1.5 billion vaccines a month.  

That assessment, however, was based only on projected estimates of booster needs for seven of the world’s richest economies – and not the three dozen or so high- and upper-middle income countries that have already initiated booster campaigns. 

In response to yet another query by Health Policy Watch, Airfinity said it was trying to update its projections to include all G-20 countries – but had not yet completed the analysis as of the time of this publication.  

What is really needed, said Aylward in Monday’s briefing is more “transparency” that ensures manufacturers prioritize their deliveries of doses to the COVAX global vaccine facility – ahead of more deliveries to rich countries.

Aylward also warned about relying too much on vaccine dose donations, saying that while some 1 billion vaccine doses have been donated so far, only about 15% of those have actually been delivered.

“There is a danger that we create a perverse incentive if we keep encouraging donations,” he added, noting that donations come with many strings attached – including deliveries too close to their expiration date and a lack of choices for low-income countries about which vaccine to receive and when.  

How frequent boosters?

WHO Chief Scientist, Dr Soumya Swaminathan

In terms of how frequently boosters might be needed in the future, and for what vaccines, “the fact is that we don’t know,” added  Dr Soumya Swaminathan, WHO Chief Scientist. 

She said that key driving factors include: “The biology of the individual, the age, how strong the immune system is. 

“There is some data now to show that there is a slippage due to the protection in different vaccines at six months or so. But with Omicron, the initial data is showing that it is very successfully able to evade immune responses and therefore needs higher levels of antibodies.  

“For now, we believe boosters may be needed for people who have weaker immune systems, the older individuals who are more vulnerable. 

“And whether there will be a need for additional vaccines every year, like influenza, it’s too early to say and we really need to follow the science on that.”  

Good news on new vaccines being rolled out  

Meanwhile,  the list of WHO-approved vaccines expanded once more on Tuesday with the Agency’s Emergency Use Listing of the European-made version of Novavax’s new Nuvaxovid™ vaccine. The WHO moved followed just after approval by the European Medicines Agency (EMA) earlier Tuesday. 

The new vaccine was developed by Novavax along with the Oslo-based Coalition for Epidemic Preparedness Innovations (CEPI), and is the originator product for the Covovax™ vaccine, produced by the Serum Institute of India, that had received WHO emergency use listing last week.

Both two-dose vaccines are made using the same technologies –  using an engineered baculovirus that delivers the gene of a modified SARS-CoV-2 spike protein into the body to provoke an immune response.  The technology, while novel, is more comparable to the traditional vaccines that deliver dead or inactivated viruses rather than to the mRNA models that deliver “instructions” to the body to produce an antibody response – without delivering any part of the virus itself.   

Significantly, the Novavax vaccines remain stable at 2 to 8 °C refrigerated temperatures – making them particularly relevant for vaccine campaigns in countries with poor cold chains.

The global COVAX vaccine facility has pre-purchased hundreds of millions of doses of the new two-dose vaccine, which is based upon has scored high marks in clinical trials. 

“This new vaccine is part of the COVAX portfolio, and we hope that it will play an important role in achieving our global vaccination targets,” said Tedros. 

Sputnik V – another review in early 2022

WHO officials at the briefing also said that the Agency’s long-delayed review of Russia’s Sputnik V vaccine would hopefully move ahead early next year, providing that the Russian-based Gamaleya Institute submits updated clinical trial data, by the end of this month.   

“Providing all information is available by the end of December, we will be able to perform GMP (Good Manufacturing Practice) inspections locally on Sputnik in February,” said Dr Rogerio Pinto de Sa Gaspar, who heads WHO’s “prequalification” activity.

Reported problems in some of the Sputnik vaccine facilities earlier this year stalled the approval processes for the vaccine, which has lagged well behind Chinese, Indian, European or American counterparts. 

In November, Sputnik’s developers have reported comparative results of its vaccine efficacy in Europe – but the studies have yet to be transformed into peer-reviewed papers. 

 

Image Credits: The Financial Times .

A doctor preparing a Moderna COVID-19 vaccine jab.

In what should be reassuring news for health systems the world over,  preliminary lab results suggest that Moderna’s authorised COVID booster dose of 50 µg offers 37-fold more protection against Omicron than the first two vaccine jabs after 29 days.

And a 100 µg booster -comparable to the dose received in the first two shots – offered even more protection – boosting antibody levels 83-fold – and to comparable levels seen against the Delta variant for the existing approved booster jab.

The encouraging results for the Moderna vaccine, reported to investors on Monday, follow on a similar report from Pfizer earlier this month on laboratory test results from its vaccine booster.

It means that existing the vaccine formulation will be sufficient, for the time being, to combat the new variant, allowing production to remain focused in the near-term on rolling out more doses of the existing vaccine.

Stephane Bancel, CEO of Moderna

“The dramatic increase in COVID-19 cases from the Omicron variant is concerning to all. However, these data showing that the currently authorized Moderna COVID-19 booster can boost neutralizing antibody levels 37-fold higher than pre-boost levels are reassuring,” said Stéphane Bancel, Chief Executive Officer of Moderna, in a statement.

“Based on the strength of neutralizing titers generated by mRNA-1273, the rapid pace of Omicron expansion, and the increased complexity of deploying a new vaccine, the Company will focus its near-term efforts to address Omicron on the mRNA-1273 booster,” the Boston-based company said in a statement. “The Company will continue to assess the breadth and durability of neutralizing antibodies from the multivalent booster candidates in the months ahead.”

Moderna’s authorized booster dose of 50 µg offers 37-fold greater protection than the first two doses – albeit 2.9 fold less than that obtained from a booster against the Delta variant. A 100 µg dose offered an 83-fold boost.

Positive bellweather 

While the Moderna data has not yet been peer-reviewed, and is yet to be followed by data on the effectiveness of other COVID vaccine boosters against Omicron, it’s one more positive bellweather.

Some analysts had warned last week that rebooting global production lines for new vaccine formulations to meet Omicron head-on would be far more disruptive of global vaccine supplies for early 2022 than booster campaigns as such.

If existing vaccine production can continue uninterrupted – rather than slowing down and rebooting for a new formulation  – that will be good news for health authorities in countries busy rolling out booster doses – as well as those still trying to get more people vaccinated with their first and second dose.

In the case of the Moderna jab, the laboratory blood tests compared results from individuals boosted with one of two possible booster doses of the existing mRNA-1273 vaccine formulation – the already approved 50 μg dose and the 100 μg dose currently in Phase 2/3 trials. It also looked at two “multivalent” vaccine candidates (mRNA-1273.211 and mRNA-1273.213) designed to target previously identified variants of concern (Alpha, Beta and Delta) – but not specifically Omicron.

Neutralizing antibodies against Omicron were assessed in assays of blood samples from the recipients before and at 29 days after the booster dose. The research was conducted at laboratories of the National Institute of Allergy and Infectious Diseases’ (NIAID) Vaccine Research Center at Duke University Medical Center. A preprint submission is being prepared based on the data.

Booster doses yielded robust antibody response against Omicron – although still less than for Delta variant

All groups had low neutralizing antibody levels in the Omicron PsVNT assay prior to boosting. At day 29 post boost, the authorized 50 μg booster of mRNA-1273 increased neutralizing geometric mean titers (GMT) against Omicron to 850, which is approximately 37-fold higher than pre-boost levels.

At day 29 post boost, the 100 μg dose booster of mRNA-1273 increased neutralizing GMT to 2228, which is approximately 83-fold higher than pre-boost levels. Strikingly, the multivalent candidates boosted Omicron-specific neutralizing antibody levels to similarly high – but not higher levels than the original vaccine formulations now in use today.

On the down side, the 50 μg booster dose had 2.9 fold lower tiers of the neutralizing antibodies for Omicron, than in the case of the Delta variant.  However, the 100 μg booster dose generated neutralizing titers against Omicron at levels almost comparable to those generated by the approved, 50 μg dose against the Delta variant (2228 versus 2423).

Phase 2/3 study data of the higher booster dose of the existing formulation (mRNA-1273) among some 305 trial participants showed that it was generally safe and well-tolerated with only slightly higher adverse events.

While the results have net yet been peer-reviewed, Moderna said it would be posting a pre-print version of the study results shortly.

Despite the generally positive showing of the existing vaccine formulation, Moderna said it would continue R&D on yet a third, Omicron specific, variant vaccine (mRNA-1273.529), saying:

“Moderna’s first line of defense against Omicron will be a booster dose of mRNA-1273. Given the long-term threat demonstrated by Omicron’s immune escape, Moderna will also continue to develop an Omicron-specific variant vaccine (mRNA-1273.529) that it expects to advance into clinical trials in early 2022 and will evaluate including Omicron in its multivalent booster program.”

Image Credits: Flickr – Official US Navy.

The World Health Organization on Friday issued an emergency use listing for a novel COVID vaccine produced – in a move that should help ramp up new rounds of COVID vaccine distributions to low- and middle-income countries in coming months. 

Approval of the novel vaccine, developed by the US-based firm Novavax, and to be produced by the Serum Institute of India under licence, is long awaited because of it’s particularly high marks in clinical trials and modest cold chain requirements – the vaccine remains stable at only 2 to 8 °C. 

Some 350 million doses of the vaccine, dubbed Covovax™, have been promised to Gavi, The Vaccine Alliance, for the COVAX vaccine facility portfolio, which supplies COVID vaccines to some 93 low and middle-income countries.  

Prior to the WHO authorization, the SII-produced vaccine had so far only received authorisation for use in Indonesia, and is in the process of being approved in Japan. 

Another version of the same vaccine is also under review by the U.S. Food and Drug Administration and European Medicines Agency. 

The WHO move opens the way for the jump-starting of Covovax vaccine distribution under the COVAX framework – even ahead of the FDA or EMA approvals. WHO approval also allows low-and middle-income countries to expedite their own regulatory approval to import and administer COVID-19 vaccines. 

SII expects to manufacture 1 billion doses of Covovax in 2022 

According to reports, the Pune-based Serum Institute of India is expected to manufacture one-billion doses of Covovax for supply to low- and middle-income countries by the end of 2022.

COVAX is co-led by the Coalition for Epidemic Preparedness Innovations, Gavi and the WHO to accelerate the development and manufacture of COVID-19 vaccines, along with fair and equitable access for every country in the world. CEPI also invested financially in the R&D of the new Covovax vaccine. 

According to reports on the phase-3 trial of the vaccine in North America, Covovax was 90.4% effective against infection and was 100% effective against moderate to severe illnesses. The shot has proven effective against COVID-19 infection in the United Kingdom and South Africa, according to the New England Journal of Medicine. 

“This listing aims to increase access particularly in lower-income countries, 41 of which have still not been able to vaccinate 10% of their populations, while 98 countries have not reached 40%,” said Dr Mariângela Simão, WHO Assistant-Director General for Access to Medicines and Health Products in a press release. 

First Of A Kind Vaccine

The vaccine is the first of a different class of COVID-19 vaccine – a protein-based vaccine and one would need two doses of it for protection against the virus.

The vaccine is produced using an engineered baculovirus that contains a gene for a modified SARS-CoV-2 spike protein. 

“With robust data on safety and efficacy against several variants, strong potential in mix and match and booster regimens, a nine-month shelf life, and standard storage temperatures, this vaccine can be used in a variety of contexts and will provide countries with another critical option in the quest to protect their populations,” said Dr Seth Berkley, CEO, Gavi, the Vaccine Alliance. 

According to the press release, the originator product produced by Novavax, named NuvaxovidTM, is currently under assessment by the European Medicines Agency (EMA). WHO will complete its own assessment of this vaccine once the EMA has issued its recommendation.

The Technical Advisory Group for Emergency Use Listing that is convened by the WHO determined that the vaccine meets WHO standards for protection against COVID-19 and that the benefit of the vaccine far outweighs any risks, and that the vaccine can be used globally, according to the press release. 

The vaccine was assessed under the WHO’s EUL procedure based on the review of data on efficacy, quality, safety, a risk management plan, programmatic suitability, and manufacturing site inspections carried out by the Drugs Controller General of India.