a single ‘breakout mutant’ shouldn’t make a vaccine useless

Several variants of the coronavirus have emerged in recent weeks that have worried scientists. The variants, which were first identified in the UK (B117), South Africa (B1351) and Brazil (P1 and P2), have several mutations in the spike protein – the small projections on the surface of the virus which help it to cling to humans. cells. This protein is the target of all COVID vaccines being deployed. So, will vaccines protect us from these new variants?

Viruses are often not very good at making identical copies of themselves. This means that each time they replicate, changes or “mutations” in their genetic sequence can occur. Most of these mutations are harmless and have no effect on the virus. However, a small minority can allow the virus to avoid being recognized by components of our immune system. These mutations are called “escape mutants”.

For months, scientists predicted that mutations in the SARS-CoV-2 spike protein could emerge and prevent antibodies from being effective. Until recently, this was mainly studied for drugs called monoclonal antibodies. These are treatments with artificial antibodies, such as REGN-COV2, developed by Regeneron. A spike protein monoclonal antibody recognizes only one part of the spike. This means that a single mutation could, in theory, prevent the antibody from binding and neutralizing the virus.

A multifaceted response

However, our own antibody response to the spike protein, either from infection or vaccination, is made up of many different antibodies – we produce a “polyclonal” response. This means that many different B cells (white blood cells that make antibodies) are activated – and all of them make different antibodies. It is therefore highly unlikely that a new viral variant will appear suddenly and cannot be recognized by any of our vaccine-induced antibodies.

But what if there is a partial decrease in the effectiveness of antibodies against new virus variants? Several teams of scientists around the world have worked tirelessly to test whether the antibodies of vaccinated people are less able to recognize new variants of the virus.

Scientists at the University of Cambridge studied a small group of people vaccinated and identified some reduction in the ability of their antibodies to neutralize the variant identified in the UK (B117). Likewise, a slight reduction in neutralization of the variant found in South Africa has been reported in the United States (B1351). But what do these lab results really mean to people who have been vaccinated?

Right now it is very difficult to look at the lab data and predict what will happen in humans. First, we don’t know the minimum number or “titer” of effective antibodies needed to protect a person from the virus. If the antibodies induced by the vaccine are “excellent” against the original virus but only “good” against the variant, is this sufficient? The answer is not yet known for sure, but mRNA vaccine maker Moderna is confident the answer will be yes.

Second, laboratory tests performed on these variants only measure antibodies. Despite this, we know that T cells play an important role in protective immune responses against SARS-CoV-2. At present, it is not known what effect variants of the virus will have on T cells. Although, since the mechanisms of viral recognition by antibodies and T cells are very different, it is reasonable to assume that mutants exhaust will respond differently. So even though a virus variant can avoid certain antibodies, there should still be T cell activity.

On a more reassuring note, scientists widely agree that it is highly unlikely that a few viral mutations will render current COVID vaccines unnecessary. However, mutations can make these vaccines less effective overall. One solution is to include additional viral proteins in vaccines, which induces a more diverse immune response. Another solution is to update the genetic sequence of the spike protein in vaccines at regular intervals, a strategy already explored by Moderna.

In any case, future vaccines under development will need to be effective against an evolving virus and continued surveillance of vaccinated populations will be essential.