Vaccine efficacy on variants

The emerging of new COVID variants around the globe is raising concerns on whether these might blunt the efficacy of current vaccines.

Professor Gilda Tachedjian, a virologist at the Burnet Institute and president of the Australian Virology Society, says a mutation becomes concerning when the virus becomes able to escape the immune system’s neutralising antibodies, which are generated during natural infection or elicited by vaccination. That means that a variant might potentially increase the risk of reinfection and lower vaccines’ efficacy.

Mutations can happen in any part of the genome, but in SARS-CoV2, the spike protein on its surface is the most critical part of the virus because here, a mutation can make a huge difference in the way the virus interacts with human cells and antibodies.

The spike is a chain of amino acids that fold in a particular way to allow the virus to bind to human cell receptors ACE2. In the variant first detected in the UK (B1.1.7) for example, a single change in the genetic code switched one amino acid for another, making the protein fold in a slightly different way. That minor shift makes the spike fit a little better into the ACE2 receptor.

Currently available vaccines elicit neutralising antibodies that bind the spike protein on different sites, blocking the virus from attaching to ACE2. If a variant presents a change in the spike’s shape, this might evade neutralising antibodies generated through vaccination. 

To understand if a variant remains susceptible to a vaccine, scientists extract serum – the liquid component of blood that contains antibodies – from vaccinated people. They then combine it with the variant to see if the antibodies can block the virus from infecting cells.

Serum testing of the Pfizer and Moderna vaccines on the B.1.1.7 variant indicates that the two mRNA vaccines remain effective. However, for the B.1.351 variant first identified in South Africa, serum testing shows a six-fold reduction in antibody activity.

Serum testing gives a signal, says Tachedjian – it’s an indication that efficacy might be lower than against the original strain. “A six- or seven-fold reduction is something you need to be aware of, but it’s not a straightforward relationship,” she says. “It’s more complicated.”

Serum testing only looks at antibodies, which are only one part of the immune response. A cell-mediated response is thought to play an essential role in avoiding severe infection. Cell-mediated immunity is an immune response that does not involve antibodies. Instead, it involves the activation of cytotoxic T-cells that can kill cells that the virus has infected.

“If vaccines give you really high-key neutralising antibodies, they might not be 100% protective against variants, but you do get some protection,” says Tachedjian. “But with time, the variants aren’t going to be effectively blocked by the immune response generated by the vaccines or by natural infection. And so eventually, we’re going to need to update our vaccines.”

Like flu vaccines that are updated yearly to account for new mutations of the influenza viruses, we might need periodic boosters of COVID-19 vaccines to include future emerging variants.

“The vaccines themselves are not the magic bullet,” says Tachedjian. “They are part of the solution, but we will still need to exercise social distancing, wearing masks, washing hands, good ventilation in enclosed spaces if we want to really drag down the infection.”