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: 309223

Reported Deaths: 7153
CountyCasesDeaths
DeSoto21005250
Hinds19989411
Harrison17590303
Rankin13388277
Jackson13169243
Madison9965212
Lee9900170
Jones8319161
Forrest7554149
Lauderdale7232237
Lowndes6306144
Lamar614685
Lafayette6081118
Washington5296133
Bolivar4778130
Oktibbeha458097
Panola4461103
Pearl River4447142
Warren4310119
Marshall4302103
Pontotoc417672
Monroe4063132
Union405175
Neshoba4009176
Lincoln3892109
Hancock373785
Leflore3471124
Sunflower332090
Tate325984
Pike3226105
Scott311973
Yazoo305369
Alcorn301566
Itawamba297977
Copiah294365
Coahoma290779
Simpson290486
Tippah285368
Prentiss276659
Marion266479
Leake262473
Wayne261541
Grenada257385
Covington255380
Adams247082
Newton246161
George238947
Winston226181
Tishomingo222867
Jasper220248
Attala213673
Chickasaw205857
Holmes187272
Clay183354
Stone179733
Clarke178177
Tallahatchie176240
Calhoun165632
Yalobusha160236
Smith159734
Walthall131143
Greene129633
Lawrence126823
Noxubee126634
Montgomery125842
Perry125238
Amite121041
Carroll121026
Webster113932
Jefferson Davis105932
Tunica103425
Claiborne101430
Benton97525
Kemper95728
Humphreys94732
Franklin83123
Quitman78916
Choctaw74417
Wilkinson65329
Jefferson64928
Sharkey49817
Issaquena1686
Unassigned00

Alabama Coronavirus Cases

Cases: 522512

Reported Deaths: 10790
CountyCasesDeaths
Jefferson755371494
Mobile39129799
Madison34124500
Tuscaloosa25408444
Montgomery24059573
Shelby23225242
Baldwin20730302
Lee15638166
Calhoun14358311
Morgan14171273
Etowah13705348
Marshall12012220
Houston10416279
Elmore10024203
Limestone9862148
Cullman9509191
St. Clair9486236
Lauderdale9280233
DeKalb8762183
Talladega8127173
Walker7151276
Autauga6763106
Jackson6762110
Blount6532133
Colbert6236132
Coffee5436113
Dale4781111
Russell431239
Franklin421382
Chilton4130110
Covington4069115
Tallapoosa3922148
Escambia390374
Dallas3528150
Chambers3519122
Clarke347360
Marion3076100
Pike306676
Lawrence296395
Winston273272
Bibb256761
Marengo248561
Geneva246475
Pickens233259
Barbour227155
Hale218675
Butler213268
Fayette209660
Henry188444
Cherokee182744
Randolph177841
Monroe173140
Washington165538
Macon156548
Clay150255
Crenshaw149557
Cleburne147041
Lamar140034
Lowndes137353
Wilcox124727
Bullock122040
Conecuh109728
Perry107726
Sumter103332
Coosa99428
Greene91434
Choctaw58824
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