The 6 vaccines we’ll use to battle COVID-19 with a push toward herd immunity

See the differences between the offerings

ORLANDO, Fla. – As of right now, the U.S. is in an uphill struggle of getting vaccines into the arms of citizens and slowing the spread of COVID-19. It’s not only a case of demand outpacing supply, but complicating the rollout are both a bottleneck of getting injections into the arms of patients and reserving enough doses for follow-up shots.

Much has been written about “herd-immunity,” the phenomenon that occurs when a majority of a population -- the herd -- develops a resistance -- the immunity -- to a particular pathogen, in this case, COVID-19. Rather than waiting on people to naturally develop that immunity, which could take decades if not centuries, society is placing a lot of faith in the development of man-made vaccines.

Six companies were chosen by the U.S. government in summer 2020 under Operation Warp Speed to develop vaccines to limit the spread of COVID-19 and promote herd immunity. One of the companies, a joint effort between Merck and IAVI USA dropped out on Jan. 25, 2021. The Merck initiative had received $38 million in funding from the U.S. government.

So, who are the companies and what are the details about the vaccines the U.S. is using to combat COVID-19?

Pfizer/BioNTech BNT162b2

Developed in conjunction with the German drug company BioNTech SE, Pfizer’s BNT162b2 was the first vaccine to be approved by the Food and Drug Administration for early adoption emergency use, which happened on Dec. 11, 2020. The Pfizer/BioTech drug is a pathogen-free mRNA, or messenger RNA, vaccine. Instead of using actual parts of a live virus to trigger an effective immune response, mRNA drugs use small synthetic pieces of genetic code to push the body into producing protective antibodies. Once the vaccine is introduced into the body, in the simplest of terms, mRNA vaccines trick immune systems into creating a small amount of COVID-19′s “spike protein,” which in turn triggers the production of protective antibodies effectively shielding humans from COVID-19.

BNT162b2 is the first-ever FDA-authorized mRNA vaccine. It’s proven to be 95% effective in combating COVID-19 in clinical trials. If there’s one drawback to the vaccine it’s that the drug needs to be shipped from the Midwest since Pfizer manufactures BNT162b2 in either Kalamazoo, Michigan or Pleasant Prairie, Wisconsin in “ultra-cold” thermal shippers to remain effective. How cold? Try -94 degrees Fahrenheit and the thermal shippers are packed with dry ice. Once the vaccine arrives at its location, it can be removed put into an ultra-cold freezer to remain good up to six months, kept in the thermal shipper to remain good for up to 30 days or put in a regular fridge at 36-46 degrees Fahrenheit to remain good for up to five days.

Like most of the vaccines on this list, it takes two doses of BNT162b2 for the best results. Doses can be spaced apart in as little as 21 days or as far apart as 42 days.

One last note on Pfizer: Technically, by the U.S. purchasing and distributing vaccine doses from the company, Pfizer is part of Operation Warp Speed. It should be noted, however, that unlike the other companies in this story, Pfizer took no research and development funds from the U.S. government to develop its vaccine. Company CEO Albert Bourla said part of the initial decision not to take U.S. money or initial funding from any other government was to “liberate our scientists (from) any bureaucracy” and to “keep Pfizer out of politics.” And although Pfizer didn’t take any developmental money, its partner BioTech did receive $445 million in funding from the German government.

Moderna mRNA-1273

Another mRNA vaccine, the Moderna vaccine, proved to be 94.1% effective against preventing COVID-19 infection in clinical trials. Moderna’s vaccine was the second to be approved by the FDA for emergency use, which happened on Dec. 18, 2020 and like the Pfizer vaccine takes two doses for full effectiveness.

Unlike the Pfizer vaccine, Moderna’s doses do not need to be stored in ultra-cooled refrigeration units, but they do need to be shipped frozen. Because the mRNA in Pfizer’s vaccine is encased in what is known as lipid nanoparticles, it must be stored in freezers at an aforementioned temperature of at least -94 degrees Fahrenheit. Moderna’s vaccine, first frozen in temperatures between -13 to 5 degrees Fahrenheit, can be stored in refrigerators for up to 30 days at 36 to 46 degrees Fahrenheit and can be kept at room temperature for about 12 hours. One other difference between the Pfizer and Moderna vaccines: doses for mRNA-1273 must be spaced apart at least 28 days versus 21 days for Pfizer’s BNT162b2. The CDC said Moderna vaccinations can be spaced out for a maximum of 42 days, like the Pfizer vaccinations.

And some little-known facts about Moderna and its vaccine: work on mRNA-1273 began as early as Jan. 13, 2020, it was finished in 25 days, it was shipped to the NIH in 42 days and it became the company’s first drug brought to market. And remember the video and photos of the first woman getting a vaccine shot in Seattle way back in March 2020? The shot she received was of the Moderna vaccine.

Janssen Biotech, Inc. Ad26.COV2.S

Janssen’s vaccine -- Janssen is a division of Johnson & Johnson -- is what is known as a viral-vector vaccine, not like the Pfizer and Moderna mRNA vaccines. Viral-vector vaccines don’t bond with synthetic pieces of genetic code, but instead hitch a ride or piggyback off of a genetically disabled adenovirus. Adenovirus 26 is the backbone of Janssen’s COVID-19 vaccine and was first used successfully with the company’s Ebola vaccine.

Viral-vector technology is not only being used by Johnson & Johnson, but is also the building block for Russia’s Sputnik V and Sputnik Light vaccines as well as China’s CanSino Biologics vaccine.

One major difference with Janssen’s vaccine compared to other U.S. vaccines is that J&J is shooting for Ad26.COV2.S as a one-and-done instead of two doses. The obvious advantage to just one dose is not only cost-effectiveness, but one dose eliminates the need for follow-up booster shots, generally unknown territory for biotech companies developing COVID-19 vaccines. China’s CanSino Biologics is also a one-dose vaccination and was adopted by Mexico as the world’s first one-dose-anti-COVID-19 vaccine with emergency use approval in early February.

That single-shot-strategy, however, may hamper the Janssen’s vaccine as during the last week of January, the company reported the vaccine’s efficiency showed some disappointing results depending on geography. In testing, extremes showed the efficacy rate fluctuated from 72% in U.S. trials to 66% in Latin America to 57% when tested in South Africa. Johnson & Johnson’s bottom line for the vaccine as of Jan. 29: Ad26.COV2.S has a 66% overall efficacy rate in preventing moderate to severe illness and 85% protection against the most serious symptoms, which is still way better than no vaccine at all. The company was also looking into how two doses could be even more effective. One very interesting outcome from Janssen’s clinical trials is that their vaccine produces less severe side effects than the Pfizer and Moderna equivalents.

Janssen’s clinical trials involved more than 60,000 volunteers worldwide. Its vaccine can also be stored in a regular refrigerator for up to six months and does not need ultra or super-cooling.

“The road to EUA (emergency use authorization) for Ad26.COV2.S was as follows. On Feb. 4, Janssen Biotech submitted an application to the U.S. Food and Drug Administration for emergency use authorization. Twenty days later on Feb. 24, the FDA released its favorable assessment of the vaccine. Two days afterward, the FDA approved the use of Ad26.COV2.S on Feb. 26 and the following day the vaccine was given the go-ahead by the Food and Drug Administration for emergency use authorization.

Total time from application to EUA approval: 23 days.

Two days after the Janssen vaccine was approved for EUA, the Biden administration announced they had brokered deals to get Merck on board with producing and distributing Ad26.COV2.S. The deal, similar to the one between Sanofi and AstraZeneca (see below), helps boost J&J’s domestic production, signaling the confidence the White House has in the one-dose vaccine. Sanofi announced in late February it would help Janssen with final production and bottling of vials in Europe. J&J/Janssen originally told the Biden administration it could immediately ship about 20 million doses by the end of March and another 100 million by summer.

AstraZeneca/Oxford AZD1222 (formerly ChAdOx1 nCoV-19)

Like J&J’s vaccine, AstraZeneca/Oxford’s vaccine also uses vector vaccine technology, hitching a ride on a non-synthetic virus, in this case, also an adenovirus or common cold virus, to introduce the coronavirus spike protein into the body and trigger an immune response. By the way, don’t worry, you won’t catch a cold just because the AstraZeneca vaccine uses a cold virus; genetic modifications have disabled all the dangerous bits.

Similar to the Pfizer and Moderna shots, patients will need two doses for full effectiveness. Like the Moderna and Janssen vaccines, but not Pfizer’s vaccine, AstraZeneca’s vaccine can be stored at 36 to 46 degrees Fahrenheit. AstraZeneca’s vaccine also has a shelf life in a refrigerator of up to six months. The company believes the two shots for patients to be most effectively immunized can be spaced out by up to 12 weeks.

In late November 2020, AstraZeneca issued a preliminary report that its vaccine had an average 70% effectiveness in clinical trials in Brazil and the United Kingdom. But one of the oddities during the trials is that two different doses were administered to volunteers producing two different efficacy rates. When two full doses were administered, the efficacy rate was 62%. But when that first dose was reduced by half, and then followed up by a full dose a month later, the efficacy rate shot up to 90%.

On Feb. 3, researchers at AstraZeneca and the University of Oxford issued a follow-up, non-peer-reviewed report that a single full dose of its vaccine was 76% effective in preventing infection from the COVID-19 virus. The announcement led to speculation that AZD1222 could be adopted by some countries as a one-dose vaccine as the team also noted that effectiveness only went up to 82% when two full doses were spaced out by 12 weeks. Additionally, researchers believe the vaccine could reduce the transmission of the virus from person-to-person, the first time that claim had been made by any of the vaccine manufacturers.

But on Feb. 7, South Africa stopped administering doses of the AstraZeneca vaccine saying the vaccine offered “minimal” protection against the country’s B.1.351 variant, also known as the 501.V2 variant. AstraZeneca responded by saying it would develop a modified version of its vaccine by the fall. Vaccines by both Janssen and Novavax also were less effective in protecting people against the South African variant. According to CBS News, South Africa had 1.5 million doses of AZD1222 that are set to expire in April.

So, by the beginning of 2021, AstraZeneca and Oxford had a workable vaccine. But testing of the number of doses, quantity of vaccine in those doses and timespan between doses -- if there were two instead of one -- led to more questions than conclusions about what exactly was the right combination that would make AZD1222 most effective. And to top it off, the vaccine was not as effective against a dominant strain of COVID-19 in one of the world’s most populous countries.

The European Union granted emergency authorization use of AZD1222 on Jan. 29 as well as AZD1222 previously being approved for emergency authorization use in the U.K. on Dec. 30, 2020. As outlined in the previous Janssen section, when the drug comes up for use in the U.S. it will go through a four-step approval process: application for approval, FDA assessment, FDA approval and then FDA emergency use authorization.

The last three steps most likely will come in a three to four day period. The timeline between step one and step two can be anywhere from two-and-a-half to four weeks.

Novavax NVX-CoV2373

Novavax, headquartered in Maryland, is one of four U.S.-based biotech companies on this list, the other three being Pfizer, Moderna and Johnson & Johnson. NVX-CoV2373 is an adjuvanted recombinant protein-based subunit vaccine, differing from the mRNA vaccines of Pfizer and Moderna and the viral-vector vaccines of Janssen and AstraZeneca.

Briefly, an adjuvanted recombinant protein-based subunit vaccine combines all or just part of the gene from a virus, in this case a version of the SARS-CoV-2 spike protein, with an immune-boosting compound called an adjuvant. Novavax uses a patented saponin-based one called Matrix-M™. The man-made “de-tuned” combination is then inserted into a baculovirus, which is a virus that’s bad for insects but harmless to humans and plants, and injected into the body to trick the immune system into naturally making antibodies that can fight off COVID-19.

Though all of this sounds a little cutting-edge, Novavax is taking a tried-and-true approach to its fight against COVID-19 as this type of direct protein delivery technology is used for modern HPV, hepatitis B and flu vaccines. The company also has a lot of experience working with other coronavirus variants, including the Middle East respiratory syndrome.

Like the Pfizer, Moderna and AstraZeneca vaccines, Novavax’s vaccine requires two doses. However, unlike Pfizer, Novavax says its vaccine can be stored in a regular refrigerator between 36 and 46 degrees Fahrenheit and is good for up to 90 days.

In late January, Novavax reported NVX-CoV2373 achieved an efficacy of 95.6% in testing in the U.K. against the original COVID-19 strain and 85.6% against the more powerful B.1.1.7. U.K. variant. Less encouraging but somewhat mixed-results were recorded with Novavax’s effectiveness against the B.1.351 South Africa variant. In testing, NVX-CoV2373 had an overall efficacy of 49.4% that rose to 60% with those who were HIV-negative.

U.S. and Mexico testing are currently underway for NVX-CoV2373 with the company shooting for 30,000 participants by the middle of February. Because of this timeline, look for Novavax to possibly be approved outside of the U.S. first following a similar path as AstraZeneca’s AZD1222.

Sanofi Pasteur/GlaxoSmithKline Recombinant SARS-CoV-2 Protein Antigen + AS03 Adjuvant

The unnamed Sanofi Pasteur and GlaxoSmithKline vaccine brings together one French and one British-based biotech company to produce another adjuvanted recombinant protein subunit vaccine. For this vaccine, Sanofi/GSK uses its own AS03 squalene-based vaccine adjuvant to kick-start the body into making antibodies to fight COVID-19. This technology is similar to what Sanofi uses for its seasonal influenza vaccines. The company is also working on a second vaccine using mRNA methodology but won’t be ready for clinical trials until later this year.

In July 2020, the United Kingdom signed a deal with Sanofi/GSK for a reported £500 million to provide 60 million doses for U.K. citizens.

In mid-December 2020, Sanofi/GSK announced its COVID-19 vaccine wouldn’t be distributed until late 2021. Su-Peing Ng, global medical head for Sanofi Vaccines, believes the problem can be traced back to “an inadequate formulation of the vaccine,” resulting in less-than-promising results in older adults. But with every problem comes a silver-lining: On Jan. 27, Sanofi announced it would use its Frankfurt facility to bottle and distribute 125 million doses of the BNT162b2 vaccine made by rivals Pfizer and BioTech.

On Feb. 22, Sanofi and GSK announced they were starting a new clinical trial after scrubbing their previous effort two months prior. A few days later, George Washington University announced it would be participating in a Sanofi/GSK phase two clinical trial. GWU was one of 25 partner sites in the U.S. for this part of the trials; the university had also participated in Moderna clinical trials.

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