The Pfizer vaccine has a novel mechanism of action that has not been widely used before. It consists of a small section of messenger RNA (mRNA) that encodes the SARS-COV-2 spike protein, sitting within a protective oily bubble of lipid nanoparticles.7 Following vaccine administration, the SARS-COV-2 mRNA is taken up by macrophages, which then produce and present the spike protein to other immune cells.7 This mimics the immune response that would result from natural infection.
As the mRNA encodes for only the surface protein, there is no risk of macrophages producing live virus or other viral components. Like human mRNA, the mRNA contained within the Pfizer vaccine is incredibly fragile and cannot be incorporated into the recipient’s genome.
The Oxford-AstraZeneca vaccine also uses a novel technique. In this vaccine, a small segment of double-stranded DNA (dsDNA) that encodes SARS-COV-2 surface protein is ‘piggy-backed’ in a nonreplicant chimpanzee adenovirus.8 Adenoviruses usually cause a mild upper respiratory syndrome, but this specific virus, although able to enter human cells, is not able to replicate within them. After the adenovirus enters a host cell, the segment of dsDNA is transcribed into mRNA, which is used by the cell to manufacture SARS-COV-2 spike protein. This is then presented on the outside of the cell to human immune cells, eliciting the desired immune response.8
The Novavax vaccine is a protein subunit vaccine, similar to the hepatitis B and acellular pertussis vaccines. It contains purified SARS-COV-2 spike proteins produced by infected insect cells along with Matrix-M1 adjuvant.6,9 The adjuvant is included to boost the immune response to the spike protein and contains nanoparticles of saponins from the soapbox (Quillaja) tree, cholesterols and phospholipids.
Vaccine dosing and storage
All three vaccines have a two-dose schedule and will be more effective after the second dose. The Pfizer and Novavax vaccine doses are given 21 days apart. The Oxford-AstraZeneca vaccine doses are recommended by the Australian Technical Advisory Group on Immunisation (ATAGI) to be administered 12 weeks apart.10 This is because post-hoc modelling data suggest increased efficacy with a 12-week dosing schedule compared with a six-week schedule.11
The Pfizer vaccine has complex transport and storage requirements. A −80°C freezer is needed to keep it stable.12 It is delivered in ‘packs’ of 190 vials, each vial containing five to six vaccine doses.12,13 The Pfizer vaccine can remain viable in the freezer for six months, but after thawing to refrigerator temperatures it must be used within five days.12 To limit wastage, patient appointments for vaccination are needed.
The Oxford-AstraZeneca and Novavax vaccines can be safely stored in the standard refrigerators (2 to 8°C) commonly available in most hospitals, general practices and pharmacies.8,9,14 The Oxford-AstraZeneca vaccine, like the Pfizer vaccine, is supplied in multidose vials.
In the case of all three vaccines, after the vials have reached room temperature for administration, they must be used within six hours.
At the time of writing, phase III trial data are available for the Pfizer and Oxford-AstraZeneca vaccines, whereas data for the Novavax vaccine have been reported only in statements to the media. Detailed statistics on the efficacy of these vaccines from these trials, including analysis by age group, are shown in Table 1.7-9