The pandemic has spurred global development of an extraordinary number of vaccines at never-before-seen speed. More than 60 vaccines are in clinical trials on humans and 17 are in phase lll trials. Scores more are being tested in animals. All eyes in the U.S. are focused on six candidates—Pfizer/BioNTech, Moderna, AstraZeneca/Oxford University, Johnson & Johnson (Janssen), Novavax, and Sanofi/GlaxoSmithKline—selected by Operation Warp Speed for support by the U.S. government.

Pfizer/BioNTech’s vaccine received Emergency Use Authorization (EUA) December 11 and Moderna’s followed the next week. Both of these vaccines use messenger RNA (mRNA) technology. While mRNA has been explored for delivery of therapeutics and other purposes since the 1970s, COVID-19 provided the first test for the approach in vaccines.

The mRNA vaccines deliver the genetic code to produce copies of part of the spike protein unique to the virus and critical to its invasion of cells. When injected, mRNA vaccines prompt cells to produce copies of the protein. The proteins do not cause COVID-19, but they enable the immune system to recognize and attack the protein and, thus, the SARS-CoV-2 virus if exposed to it later. Once the proteins are made, the genetic material incorporated in the vaccine is destroyed.

The Johnson & Johnson vaccine uses the adenovirus 26 (Ad26) as a viral vector in a process originally developed at Beth Israel Deaconess Medical Center in Boston. Ad26 transports an attenuated version of SARS-CoV-2 coronavirus genes into cells where they provoke production of the coronavirus’s spike protein. The copies of the spike protein circulate in the body, causing an immune response and priming the system to fight the virus if exposed subsequently. Unlike the other vaccines in accelerated development in the U.S., Johnson & Johnson’s phase lll trial tested just one shot, though a second phase lll trial will see whether results improve with two doses. Johnson & Johnson could announce trial results in early January and may have sufficient data to file for an EUA later that month.

The AstraZenca/Oxford University vaccine also uses a viral vector, this time a chimpanzee adenovirus, to carry genetic instructions to produce the spike protein. The adenovirus itself can infect but not reproduce in human cells. Questions about dosage changes and the performance in older participants in its phase lll trial could push authorization of this vaccine back to late January or further.

Protein subunit vaccines include SARS-CoV-2 proteins but no genetic material. The Novavax vaccine uses recombinant nanoparticles studded with coronavirus spike proteins produced by moths plus an immune booster. Once vaccinated, our immune system identifies the proteins as invaders and ramps up production of T-lymphocytes and antibodies. The immune system will recognize the protein if it is encountered later. Novovax expects to be authorized and distributing vaccine in the U.S. early next year.

Operation Warp Speed also bet on Sanofi/GlaxoSmithKline’s vaccine, which is also the protein subunit approach. On December 11, however, the companies reported that its vaccine did not produce the desired level of response in trial participants over the age of 50 years. They will conduct a new phase ll trial with a different formulation starting in February, making it unlikely that any doses will be available before late 2021.

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