The World Health Organization (WHO) and the European Medicines Agency (EMA) recently issued emergency use authorization (EUA) for a COVID-19 vaccine produced by Novavax. Meanwhile, the company anticipates also obtaining an EUA from the United States Food and Drug Administration (FDA) in the coming weeks. As we discussed in early 2021, around the time that the COVID-19 vaccines of Pfizer/BionTech and Moderna received their FDA EUAs for administration to adults, the Novavax vaccine is produced through an older strategy than either the mRNA strategy of Pfizer/BioNTech and Moderna or the strategy of AstraZeneca/Oxford and Johnson and Johnson (Janssen) that involves DNA in an adeno-associated virus (AAV). Although the two DNA-AAV vaccines and the two mRNA vaccines are perfectly safe in addition to being effective, much of humanity, including almost 40 percent of the US population remains unvaccinated against SARS-CoV2 (the virus that causes COVID-19), partly on account of science illiteracy —specifically biology illiteracy. This makes them vulnerable to misinformation related to the molecular biology of the approved vaccines. At the same time, there are storage and other logistical issues (related to needed storage temperature and durability of batches of vaccine) attached to the mRNA vaccines that lead to challenges for distributing them in various locations around Earth.
Up against these two obstacles, it is noteworthy that the Novavax vaccine is produced through an older strategy that leads to just a protein and an attached molecule called an adjuvant comprising the business end of the vaccine. In this regard, the Novavax vaccine against COVID-19 is like the hepatitis B vaccine that is made by way of recombinant DNA technology that produces a protein from genetic sequences (genetic engineering). It does not contain any nucleic acids (DNA or RNA) that carry genetic programming for the spike protein, but rather consists of a portion of the spike protein that SARS-CoV2 uses to enter cells that it infects (rendered incapable of actually entering cells), plus the adjuvant molecule that helps it generate an immune response against the spike protein. By avoiding the genetic component (which is not harmful in any case), in a weird way, perhaps the Novavax vaccine against COVID-19 will be more appealing to some fraction of the people who have been hesitating to get vaccinated with one of the other products. Let’s review the Novavax biology.
With all of the vaccines that either have received emergency use authorization (EUA) in the United States, or the equivalent in other countries, there has been a common theme: the spike protein. Recall from my previous posts that the spike protein is one of a handful of proteins on the protein coat of SARS-CoV2 (the virus that causes COVID-19). Actually, different versions of the spike protein are on all coronaviruses; this family of viruses gets its name, because the spike protein sticks out kind of like the spikes on the crown of the Statue of Liberty. They actually look like that when the virus is imaged with electron microscopy. They look like a crown —a corona. But not all coronaviruses cause severe disease in humans. With most of them, in fact, they only cause a cold, generally because they don’t survive at temperatures of tissues deep in the respiratory tract; they only go as far as the upper respiratory tract. But in the case of a few coronaviruses, the viruses go down to the lungs, where their spike proteins attach to cell surfaces. In the case of SARS-CoV2, the particular structure of its spike protein enables the virus to attach to a cell surface protein called ACE-2 —leading to all sorts of horrible problems that we have discussed in other posts. But it turns out that the spike protein is also very immunogenic. It stimulates the immune system and so it it has been the top choice to use in vaccine strategies for creating an immune response against the virus. This does not mean that other SARS-CoV2 surface proteins cannot be used, but all of the vaccines that we have discussed in connection with this disease take a spike protein approach, as does the Novavax vaccine.
With both DNA-AAV and mRNA vaccines, the spike protein is delivered to the surface of affected cells. In all affected cells, the spike protein on the cell surface is attached to a normal cell surface protein called MHC-1. In APCs, the spike protein also ends up on the surface attached to another protein called MHC-2, which is very important for generating immunity by stimulating what’s called a T-cell response. Being the spike protein itself plus an adjuvant molecule, the business end of the Novavax vaccine, once injected, moves through the blood and reaches the the surface of antigen-presenting cells, stimulating an immune response. As with most of the other vaccines that we have discussed, the Novavax vaccine was developed as a two-dose regimen (you get the first shot and about a month later the second shot), but will probably evolve to at least a three-dose regimen, meaning that the “booster” is not so much a booster as a third dose.
