Is the sequence of the spike protein different between the different vaccines?


A: Yes! The AstraZeneca vaccine uses the wild-type protein sequence while the Moderna, Pfizer/BioNTech, Novavax and Janssen include a slight modification to the sequence meant to stabilize the protein in the “prefusion” conformation.

SARS-CoV-2 uses the spike protein to enter the human cell. The spike protein is like a key that the virus uses to open the door of the cells. The goal of the vaccines is to develop antibodies against the spike protein. By developing antibodies against it, the antibodies can cover up the key/spike protein to prevent it from entering the cell. The neutralizing antibodies are the antibodies with this superpower to prevent the virus from entering the cell and prevent COVID19 disease.

Before the virus enters the cell, the spike protein is in the “prefusion” conformation. After the virus attaches to a cell, the spike protein goes into an elongated “postfusion” conformation in order to trip the lock and enter the cell. When the spike protein is attached to a coronavirus it is relatively stable and stays in conformation. However, when the wild-type spike protein is expressed by human cells from vaccination, the spike protein can be floppy and shift from pre-fusion conformation to the post-fusion conformation. Only antibodies that recognize the pre-fusion conformation have the power to be neutralizing.

While working on the MERS vaccine, a different coronavirus prior to the current SARS-COV2 pandemic, a team of scientists discovered if they added two amino acids (protein building blocks) it can stabilize its spike protein into the pre-fusion conformation. This way more of the antibodies can be neutralizing.

The Moderna, Pfizer/BioNTech, Janssen (Johnson and Johnson) and Novavax vaccines contain the modified spike protein sequence that stabilizes the spike protein into the pre-fusion conformation. Scientists think that keeping the spike protein in the pre-fusion conformation may lead to more neutralizing antibodies. Time will tell whether the vaccines with the locked prefusion conformation spike protein will be more effective against SARS-CoV2 compared to the other vaccines which contain the wild-type spike protein.

The tiny tweak behind COVID-19 vaccines

Distinct conformational states of SARS-CoV-2 spike protein

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