__________________________________
Data are still very limited when it comes to vaccination against COVID-19 during pregnancy, but pregnant women are being vaccinated little by little, because there is no particular reason why any of the COVID-19 vaccines that are available —or soon to be available— should be harmful, either during pregnancy, or breast feeding. This includes the concern about the placenta and infertility that we discussed and debunked, here on The Pulse. Therefore, since we have been making the rounds on the different COVID-19 vaccines, today, let’s take a look at the latest vaccine to release some encouraging news, the vaccine from the Novavax company.
As with previous posts, hold onto your seats, get some popcorn, or coffee, or whatever you enjoy, because again we get to travel through the beautiful world of molecular 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.
But there are different tactics for utilizing the spike protein. One tactic is that you can deliver a piece of DNA into the nucleus of some body cells. This is done with a type of adenovirus —a virus that, unlike coronaviruses, uses DNA as its genetic material— in which the DNA encoding the spike protein is added in place of the adenovirus’ normal DNA. The spike protein DNA gets into a variety of different cell types, including antigen presenting cells (APCs). This starts a process that results in immunity against the spike protein and thus against SARS-CoV2. The AstraZeneca/Oxford and the Johnson and Johnson vaccines for COVID-19 both use this DNA virus tactic.
Another tactic is that you can deliver a piece of RNA, encoding the spike protein, not into the nucleus of body cells, but into the cytoplasm, the part of the cell outside the nucleus. This is done by enclosing the strip of RNA, not in a virus, but in a lipid nanoparticle. Such particles are made of the same material of which cell membranes are composed, so the particles literally become part of the membrane and when they do, the RNA enters the cell. Various types of cells receive the RNA, including myocytes (muscle cells), but some APCs also receive it. Once inside your cells, the RNA is used to make spike protein, which, as with the DNA vaccines, ends up on the surfaces of cells. The Pfizer/BioNTech and Moderna vaccines both work this way.
With both DNA and RNA 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.
The Novavax vaccine, which recently was announced to be 89 percent effective (a good result) against the development of COVID-19 disease, contains neither DNA, nor RNA. Rather it is the spike protein itself. It was produced with molecular methods involving DNA and RNA, and what gets injected is an engineered protein. And after it gets into your blood, guess where it ends up. You guessed it, on the surface of APCs, meaning in connection with MHC-2. And that means that the immune system is triggered. As with most of the other vaccines that we have discussed, the Novavax vaccine is a two-dose regimen. You get the first shot and about a month later the second shot. Stay tuned as we learn more.
