Laboratories race against time to adapt vaccines to new variants

BarcelonaLike all viruses, the one that causes covid-19 mutates. In a natural and random way, each time it replicates, small genetic alterations are produced that either have no importance (most of them), or they weaken the virus - or they can make it more infectious and lethal. Last month, three new variants were detected in three different parts of the world (the UK, South Africa and Brazil) which have spread rapidly, despite movement restrictions. These mutations raise an urgent question: do vaccines that were designed to fight the original version of the virus work against these new variants? More worryingly, can the virus continue to evolve into a form that escapes the vaccines that already being administered?

"The situation is worrying, because we are seeing that the antibodies generated by the available vaccines can also block the British variant, but work worse against the Brazilian and South African ones" Julià Blanco, a researcher at the Germans Trias i Pujol Institute and IrsiCaixa, explains. "This does not mean that the vaccines are not effective, but that it is more difficult for them to block the virus. It is a problem of correlation of forces. Imagine that the virus weighs 100 grams: everyone can lift it, but if it weighs ten kilos there will be people who cannot do it, and if it weighs 100, then almost no one can. The same thing happens with the immune system". Blanco believes that "the virus is becoming more difficult to neutralize, but we can still control it. The danger is that it continues to change and some of the mutations end up being resistant to the vaccine".

All vaccine manufacturers have found this week that their preparations, although they continue to be effective, offer less protection against new variants. Friday was the American Johnson & Johnson, the only one that has developed a single-dose vaccine: its preparation has shown an efficacy of 72% in the United States, which drops to 57% in the case of South Africa, where the variant predominates. Studies suggest the same for the Pfizer-BioNTech, Moderna and Novamax preparations. The South African variant has already been detected in 31 countries, including Spain, after on Thursday the first case was diagnosed in Vigo.

"The virus has no intentionality: it mutates randomly and the changes that are favorable are those that are imposed by natural selection. That's why we see that it has evolved in the same direction in three different parts of the world", Blanco says. The key, for experts, is to reduce transmission because "the more it is transmitted, the more likely it is to mutate". The problem is that, with at least 100 million infections worldwide (these are the diagnosed cases, the real figure is probably much higher) the virus has many opportunities to change. "We're giving it a head start", Blanco concludes.

Adapting vaccines

Vaccines that work with messenger RNA can be adapted to the new variants, for which genetic mutations have already been identified in a matter of weeks. What remains unclear is what kind of approval the reformulated vaccines, which have only slight modifications, would have to go through. Monday Ugur Sahin, head of BioNTech, the German drugmaker that developed the Pfizer vaccine, explained that they are already talking to regulators about what kind of clinical studies will be needed to demonstrate the efficacy of the new versions rather than having to start the process all over again from scratch. He also hinted at the option of injecting a third dose to boost the immune response. This is what already happens every year with the flu vaccine, which is modified according to new strains without having to go through the costly approval process required to bring a new drug to market.

Moderna has also announced that it is developing new versions that better block new variants: "We try to stay ahead of the curve in case we need to, we take it as an insurance policy", Tal Zaks, Moderna's chief medical officer, said.

Technologies and variants

Salvador Macip, a doctor and researcher at the University of Leicester and the UOC, stresses that vaccines based on classical technology may be more responsive to new variants: "Those that use the whole inactivated virus, such as the three that are being given in China and the one that has begun to be distributed in India, are more likely to recognize all forms of the virus, because they generate a response that does not depend only on the protein that is mutated in these three variants". In this sense, the professor of biology at the UPF, Cristina Pujades, stresses that the coronavirus is "very vaccinable" because it has a relatively simple structure and, as has been seen, it is easier to develop vaccines that neutralize it than other more complex viruses. And she stresses that "perhaps we need to think about a range of vaccines that could be used at different times of the pandemic and of life".

Other specialists warn that it is not only the antibodies generated by vaccines that neutralize the virus that need to be taken into account. "Vaccines generate other antibodies and also cellular immunity, and what counts for the proper functioning of the immune system is the sum of all this", Joaquim Segalés, researcher at IRTA-CRESA and the Autonomous University, says. Between concern and optimism, experts agree on the message that the less the virus circulates, the less headaches it will cause. "The more it circulates, the more likely it is to mutate. If we want to reduce the likelihood of new variants emerging that may be resistant to vaccines, we have to achieve a level of herd immunity. We have to avoid the circulation of the virus and that is why we need an important level of herd immunity or we will have to continue with social distancing measures, use of face masks, etc. When we talk about herd immunity, we are talking about 70% or 80% of the world's population, because if we continue as we are doing now, only vaccinating a part of the world, there will be other places, very populated, where the virus can continue to circulate". So the message is unanimous: we must vaccinate systematically, quickly, in the right order, everywhere, and without stopping.