Third dose or Delta variant vaccine?

Some people are asking: Isn’t it time to adapt vaccines to variants? With the health situation deteriorating as autumn progresses, hospital admissions increasing and hospitals once again under strain, some people wonder why mass vaccination in Belgium hasn’t prevented a fourth wave. And why give a third dose of vaccine rather than a version adapted to the Delta variant?

Fuelling discussion and division in recent months, vaccines, and more particularly their effectiveness, are being questioned. So much so that even people who have been vaccinated and are convinced of the benefits of the vaccines on the market wonder why pharmaceutical companies don’t adapt them to improve their effectiveness against new variants. The possibility of adapting vaccines to variants within six weeks was indeed announced when they were put on the market. Sophie Lucas, an immunologist at the UCLouvain de Duve Institute, helps us understand the truth about the effectiveness of vaccines against variants and their adaptation at this stage.

Why is a third dose of an existing vaccine proposed instead of a vaccine adapted to the Delta variant?

Current vaccines have been developed on the basis of a pre-alpha version of the virus to allow the body to make a replica of its spike protein and, consequently, to awaken and educate our immune system to defend itself against any intruder carrying the spike protein on its surface. The spike protein is composed of more than 1,200 amino acids. Between the pre-alpha version of SARS-CoV-2 and the Delta variant that circulates the most today, only a few amino acids have changed in the spike protein. Vaccines produce many different antibodies that bind to different parts of the protein to prevent it from attaching to and infecting our cells. If the majority of antibodies produced after vaccination are still able to bind to a variant’s spike protein, the vaccines are still very effective against the variant in question. This is currently the case with the Delta variant. The reduction in vaccines’ efficacy due to a few mutated amino acids in its spike protein is real but minimal, particularly because the vast majority of antibodies can still bind elsewhere on the Delta variant’s spike protein. This needs to be monitored continuously, but for the moment there’s no point in modifying vaccines.

Why is the situation deteriorating again despite the great number of vaccinated people?

It’s now observed that the levels of antibodies produced following initial vaccination (as well as those produced following infection by the virus itself, see box) decrease over time, hence the interest in a third dose that will boost immunity against the virus and enable vaccines to be much more effective again against potential infection by SARS-CoV-2. The third dose will simply increase the quality and duration of the immunity induced by the first two doses. In general, additional doses of vaccine induce a more intense, longer lasting and more protective immune response. But the health situation we see today isn’t only related to the decline in immunity over time. It’s related to a combination of factors, including the non-negligible fraction of unvaccinated people in the population, and the variant’s ability to be much more contagious than its predecessors.

When will it be time to consider a new version of vaccines?

Mutations are monitored continuously, just like for influenza. Many people don’t know it, but the flu vaccine is a huge job each year, involving more than 200 laboratories worldwide to analyse mutations and the influenza vaccine’s effectiveness. The vaccine is adapted every year. The same will be true of SARS-CoV-2 and of its variants and the effectiveness of vaccines against them, which are under the scrutiny of many experts around the world. When the immunity and antibodies generated by current vaccines are no longer sufficient to combat circulating variants, it will be time to adapt the vaccines. But it’s not possible to anticipate this any further than we’re doing at present, because the mutations that would make vaccines insufficiently effective haven’t yet emerged. Ideally, we would like to develop a vaccine that would educate our immune system against a stable part of SARS-CoV-2 that is common to all its variants. This would be a universal vaccine.

Studies are beginning to emerge about a potential universal vaccine, such as one conducted by KU Leuven.

Many laboratories are looking for an effective vaccine against all variants. The KU Leuven study is interesting, carried out exclusively on animals, and proposes a new antigen, that is, a replica of the part of the virus that is presented to the body via vaccination. This would induce more “universal” responses, which are equally active against the alpha, beta, gamma and Delta variants. That said, the paper doesn’t directly compare the original vaccine antigen with the new vaccine antigen for protection against the Delta variant and therefore doesn’t allow us to conclude that protection against Delta specifically is better with this new antigen than the old one. Above all, it provides a solution to the reduced protection conferred by certain vaccines against the beta variant, which hasn’t become dominant in our country—owing to the Delta variant. But it could be valuable for the development of adapted vaccines in the future, suggesting that there could be a way to adapt them in a more “universal” way against future variants. This remains hypothetical at this point.

Natural immunity versus vaccine immunity

Can those who had Covid-19 rely on their antibodies to defend against future infection?
The level of antibodies in the blood following an infection or vaccination fluctuates over time. These levels should therefore be monitored very regularly, although they also vary greatly depending on the testing conditions used by each laboratory. But what makes it even more difficult to use these levels to assess our defences is that to date there is no absolute correlation between the level of antibodies in the blood and protection against infection and disease. This means we don’t know the minimum level of antibodies that should be in the blood to be properly protected. Finally, and most important, protection against disease is multifactorial and doesn’t rely on antibodies alone. It’s therefore a chimera to think that one is protected because one still has antibodies in the blood following a previous infection.

Published on November 30, 2021