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Why Oxford's coronavirus vaccine could do more for the world than other shots

In the days since Oxford University and AstraZeneca...

Posted: Nov 28, 2020 10:58 AM

In the days since Oxford University and AstraZeneca unveiled the results of the partnership's Phase 3 Covid-19 vaccine trials, a growing number of questions have emerged.

The stated 70% average efficacy was significantly lower than the 94.5% to 95% reported by the other two leading candidates, Moderna and Pfizer.

Yet this vaccine could still prove to be more valuable for the world than the other two in the coming months. If the questions over its results are answered and it receives approval, it may lead the way in providing vaccine coverage in poorer countries where it is urgently needed.

The UK government took the first step in that approval process on Friday, announcing that it had formally referred the candidate to the UK's medicines regulator for assessment.

"[T]he Pfizer vaccine is committed to its initial doses going to the EU and the US. And Moderna's supply will be tied up with the US for at least probably the first half of 2021, so in light of that, the Oxford/AstraZeneca vaccine is really good news for the rest of the world," Andrea Taylor, assistant director of programs at Duke Global Health Innovation Center, told CNN.

AstraZeneca has promised to supply hundreds of millions of doses to low and middle income countries and to deliver the vaccine on a not-for-profit basis to those nations in perpetuity. The vaccine developed at England's Oxford University is significantly cheaper than the others and, crucially, it would be far easier to transport and distribute in developing countries than its rivals since it does not need to be stored at freezing temperatures.

"I think it's the only vaccine that can be used in those settings at the current time," Azra Ghani, chair in infectious disease epidemiology at Imperial College London, told CNN.

The technology

The Oxford/AstraZeneca vaccine can be kept at refrigerator temperatures of 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit) for at least six months. Moderna's vaccine has to be stored at -20C (-4F) -- or at refrigerator temperatures for up to 30 days -- and the Pfizer/BioNTech vaccine has to be stored at -75C (-103F), and used within five days once refrigerated at higher temperatures.

"Pfizer and Moderna require freezer storage, and that just isn't in place in many settings," Ghani said.

"Cold chain" refrigeration is the standard storage used globally to deliver vaccines from central locations to local health clinics. AstraZeneca's vaccine is so far "the only one that can definitely be delivered to those systems," added Ghani.

The vaccines are based on different technology. AstraZeneca's offering -- like Johnson & Johnson's vaccine and Russia's Sputnik V -- uses an adenovirus to carry genetic fragments of coronavirus into the body.

The Moderna and Pfizer vaccines use pieces of genetic material called messenger RNA (mRNA) to prompt the body to make synthetic pieces of the coronavirus and stimulate an immune response. "This is a relatively new technology and little is known about the stability of mRNA over time," Penny Ward, chair of the Education and Standards Committee of the UK's Faculty of Pharmaceutical Medicine, told CNN.

She said that as Moderna and Pfizer build up information and manufacturing capacity, they may be able to find storage methods at higher temperatures, but the Oxford vaccine "has the potential to be able to be shipped more readily around the globe" using existing supply chains.

It will only be of value, however, if the vaccine's levels of efficacy are maintained while it's distributed in developing countries.

AstraZeneca this week said trials showed that one dosing regimen produced 62% efficacy while the other achieved 90%, giving an average of 70%. This is a good result, comparable to the flu vaccine, but not as high as Pfizer's 95% and Moderna's 94.5%. The 90% figure is based on a sampling of 2,741 participants, which is a relatively small number.

Moncef Slaoui, chief adviser to the US government's Operation Warp Speed, said this week that there were "a number of variables that we need to understand" around the dosage and age differences in the Oxford/AstraZeneca results, after which the ongoing US trial might need to be modified.

On Thursday, a spokesperson for AstraZeneca told CNN that they were currently in discussions with the FDA about including the half-strength dose regimen into their US trials, which currently has around 10,000 participants.

Ayfer Ali, associate professor of international business at Warwick Business School, said the "distribution simplicity" of the AstraZeneca vaccine could "possibly make up for the lower potential efficacy."

"The actual efficacy of the mRNA vaccines that are more fragile to transport and store may be lower in real world conditions where correct storage of each dose may be hard to verify," she added.

BioNTech said last week it was working with Pfizer to come up with a formulation that would allow storage of its vaccine at standard temperatures by the second half of 2021. Moderna this month extended its estimate for how long its vaccine could remain stable at refrigerator temperature from an estimated seven to 30 days. This, according to Moderna's Chief Technical Operations and Quality Officer Juan Andres, "would enable simpler distribution and more flexibility to facilitate wider-scale vaccination in the United States and other parts of the world."

Pledging to help

AstraZeneca has pledged 300 million doses of its vaccine to COVAX, a partnership between GAVI, the vaccine alliance; the World Health Organization; and the Coalition for Epidemic Preparedness Innovations (CEPI) for ensuring equitable distribution to 92 developing countries. The only other known vaccine developer that has made a pledge of a similar scale is Sanofi, at 200 million doses.

A GAVI representative told CNN that the Serum Institute of India (SII) and Bill and Melinda Gates Foundation would also provide up to 200 million doses of the AstraZeneca and/or Novavax candidate vaccines to lower-income countries. Moderna and Pfizer have not pledged any doses to COVAX.

This could mean AstraZeneca has more manufacturing capacity than other pharmaceuticals thanks to its links to industry giants such as the SII through CEPI.

"[AstraZeneca has] been working with manufacturing experts in that coalition to help source a variety of different manufacturing sites, and of course it's not just the vaccine itself, it's also the glass vials that it goes into, the stoppers that go on top of the bottles, and syringes and needles," said Ward.

AstraZeneca says it expects to be able to have capacity to produce up to 3 billion doses of the vaccine in 2021 on a rolling basis. Pfizer/BioNTech says it can manufacture up to 50 million doses in 2020 and 1.3 billion in 2021, while Moderna says it expects to be able to deliver approximately 500 million doses per year and possibly up to 1 billion doses per year beginning in 2021.

After calls for transparency from groups such as Medicins Sans Frontieres and Global Justice Now, AstraZeneca and Oxford confirmed that the partnership would deliver the vaccine on a not-for-profit basis until at least July 2021 worldwide, and in perpetuity to low and middle income countries.

The Oxford vaccine is cheaper than the others, at approximately $3 to $4 per dose in contrast to about $20 for the Pfizer vaccine and $32-37 for the Moderna vaccine.

"Our vaccine can be deployed quickly in existing health settings, which will help to stop the further spread of this disease while we learn more and more about how to prevent and treat it," a spokesman for Oxford University told CNN. He added that a range of vaccines would be needed and some could be more effective for different ages and populations.

"The key with any vaccine is the potential for impact on public health, including how quickly it can be distributed. Ours can be quickly and easily distributed around the world, using existing logistics, and easily stored in a fridge," he said.

Global implications

COVAX will be critical in getting the vaccine to low and middle income countries, modeling by Duke University shows. The initiative aims to provide 2 billion doses by the end of 2021 to protect high-risk groups around the world and eventually enough doses to cover 20% of those countries' populations.

However, Ghani warned that 20% was "nowhere near the ideal -- around 70% -- that we would like to see to be able to achieve herd immunity, so some countries will still fall short."

She said that it was vital for everyone that the global population is vaccinated, to enable travel and movement across borders. Rolling out the vaccine to the world could take until 2023, according to current models -- not to mention the potential need for booster shots.

"Access to safe and efficacious COVID-19 vaccines for the most vulnerable groups everywhere in the world is the only way to bring the acute stage of this pandemic under control," said Dr Seth Berkley, CEO of Gavi, as he welcomed the news on the Oxford vaccine in a statement this week.

Duke's modeling shows that while wealthier countries have purchased billions of doses in advance to increase their chances of covering their population, the developing world will be entirely reliant on COVAX.

Bill Gates said the solution was "not shaming the rich countries that are doing the natural thing of wanting to protect their people," but was to vastly increase manufacturing capacity.

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, warned that monitoring efficacy and safety issues would be an ongoing challenge in the developing world.

"There may be some adverse effects that would only be apparent in those low and middle income countries; they have different diets, they have different levels of nutrition in general, and different characteristics," he told CNN.

While Oxford's vaccine may have particular promise at this stage for helping lower income countries, there are still many caveats over the data that must be resolved before it can be rolled out.

Ultimately, it will be vital to have as many vaccines as possible, to ensure a faster recovery and limit further damage to the world.

Mississippi Coronavirus Cases

Data is updated nightly.

Cases: 245847

Reported Deaths: 5356
CountyCasesDeaths
DeSoto16717168
Hinds15748310
Harrison12806188
Rankin10334204
Jackson9996172
Lee8666135
Madison7994158
Jones6112108
Forrest5826117
Lauderdale5672174
Lowndes5186106
Lafayette482792
Lamar471162
Washington4700122
Bolivar3915105
Oktibbeha384279
Panola357274
Pontotoc356552
Monroe3463101
Union334755
Warren334692
Marshall333264
Neshoba3310149
Pearl River313891
Leflore2969104
Lincoln290185
Sunflower275868
Tate264759
Alcorn257850
Itawamba257058
Pike254876
Hancock246957
Prentiss240047
Scott238743
Copiah235649
Yazoo235054
Tippah233845
Simpson230166
Leake226764
Coahoma219054
Grenada213970
Covington207171
Marion203371
Adams200065
Winston196260
George195937
Wayne193029
Attala190958
Newton185142
Chickasaw179943
Tishomingo179059
Holmes167467
Jasper163533
Clay155632
Stone138818
Tallahatchie137033
Clarke135160
Calhoun132021
Smith117322
Yalobusha112534
Walthall110536
Noxubee108922
Greene108229
Montgomery107134
Carroll102320
Lawrence99817
Perry98631
Amite95725
Webster90024
Claiborne84125
Tunica84021
Jefferson Davis82925
Humphreys80324
Benton79722
Kemper75620
Quitman6678
Franklin64613
Choctaw59412
Wilkinson57424
Jefferson52019
Sharkey42317
Issaquena1576
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Alabama Coronavirus Cases

Cases: 414583

Reported Deaths: 5945
CountyCasesDeaths
Jefferson60842887
Mobile29590538
Madison26466183
Tuscaloosa20537267
Montgomery18562304
Shelby18181112
Baldwin15841177
Lee1212097
Morgan12002112
Etowah11488142
Calhoun10863197
Marshall10048106
Houston8405123
Cullman792294
Limestone785073
Elmore7670101
DeKalb757282
St. Clair7417120
Lauderdale740282
Talladega6036108
Walker5834176
Jackson571937
Colbert522270
Blount521980
Autauga507555
Coffee431456
Dale388278
Franklin362145
Chilton332965
Covington325567
Russell318910
Escambia309842
Dallas297988
Chambers275769
Clarke272933
Tallapoosa2591107
Pike245829
Lawrence239345
Marion238649
Winston222535
Bibb211347
Geneva196331
Marengo196329
Pickens195331
Hale172542
Barbour169636
Butler166958
Fayette164026
Cherokee158330
Henry149219
Monroe143617
Randolph137635
Washington135426
Clay124446
Crenshaw117444
Lamar116819
Cleburne115123
Macon111935
Lowndes107935
Wilcox99921
Bullock97128
Perry95019
Conecuh92820
Sumter89126
Greene75123
Coosa59814
Choctaw50824
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