Coronavirus: should vaccine formulas be updated? | The appearance of the Delta variant defeats the original versions

The vaccines the world is applying were made on the basis of the genome of the “original” virus detected in Wuhan, but the coronavirus has mutated. For this reason, doubts have been cast as to whether the available technologies would be successful in combating the newer variants of Sars CoV-2. Nowadays all eyes are on Delta, which began in India, has rolled out with particular speed in the United Kingdom and is already circulating in more than 74 countries. The worrying fact is that it is 60% more transmissible than the Alpha variant which prevailed until a few weeks ago in the European nation. This week, Israel surpassed, for the first time in months, the 100 plus points: more than 90% of infections were due to Delta; of the total, 40% were vaccinated.

To date, some the laboratories have expressed their views on the effectiveness of their formulas compared to Delta: AstraZeneca It has been reported to reach 71% with one dose and 92% with two; while Pfizer it reaches 94% and 96% respectively. the Gamelaya Center, for its part, indicated that Sputnik V is “the most effective technology against the variant” and announced that in a few days, they will release the results of their study in an international peer-reviewed journal.

In this context, although the reports of biotechnology companies generate tranquility, the authorities and referents in the field of health and science do not exclude more drastic solutions. The Minister of Science, Technology and Innovation, Roberto Salvarezza, said that “it will probably be necessary to give booster doses or to change the vaccine if it is not effective against a new variant”. The principle is simple: if the virus transforms, the tools to fight it must do the same. Now, how complex is it to change a vaccine? How to update it so that it responds more effectively to the variants that are circulating?

How are they changed?

“The coronavirus mutates but much less than other viruses like the flu. If it is decided to modify a vaccine such as Sinopharm (virus inactivated) specialists should cultivate the new virus (ie different from the “original” strain of Wuhan) which circulates mainly and from there develop a new compound, “he describes. Mario Lozano placeholder image, virologist at Conicet and specialist in vaccines. It is: inactivating the virus, purifying it, conditioning it and then distributing it for injection.

For their part, technologies which use genetic fragments of Sars CoV-2 to generate immunity, such as those designed based on RNA (Pfizer, Moderna), or those which have been developed from adenoviral vectors (Sputnik V, AstraZeneca, CanSino) are a parcel easier to modify. “These carry some of the genetic information of the virus encapsulated in a particle, either in a lipid vesicle (RNA) or in the cap which provides another inactivated virus (vectors). In these cases, it suffices to change the genetic fragment that corresponds to the coronavirus. Instead of placing the original linked to the strain that was first detected in China, they locate the one that represents the current variant, ”explains the former rector of Quilmes National University. In this line, he could be replaced without problem by the genetic information related to Delta, as well as the next ones that may emerge. In fact, the emergence of other variants of epidemiological interest such as Delta Plus or P5 (recently reported in Rio de Janeiro) has already transcended. The bad news: as long as the spread runs its course as it does, the dissemination of new variants is perfectly to be expected.

From this point of view, it raises Daniela Hozbor, biochemist and principal investigator of Conicet at the Institute of Biotechnology and Molecular Biology of La Plata: “Modifications could also be made to other proteins of interest of the virus. Pfizer and Moderna are both working to replace or add genetic material, so that the vaccine has information on old and new variants. And he maintains: “Currently, we are even talking about a vaccine called ‘pancoronavirus’ which includes all variants. Technologically updating a vaccine is very feasible, it can be done without any problem”. The scientist is referring to a kind of “universal formula” useful for all coronaviruses.

“With the modifications, the external structure of the vaccine does not change, virtually no fit or tolerance testing would be required as it would be the same as the original technology. Therefore, they could be applied quickly and not take all the time it took to design the first ones we are injecting today», Emphasizes Lozano. The change is made in a simple way, with which, between tests and authorizations, updated vaccines could be available between two and three months, according to the specialists consulted. However, the need or not to perform clinical trials with updated vaccines is a point to be resolved on which nothing is yet stipulated. “The fact of doing or avoiding clinical studies with modified vaccines is not at all regulated. Maybe more tests will need to be done, but not of the magnitude they have had with thousands of volunteers for the first generation vaccines, ”warns Hozbor.

The possibility of the virus mutating and questioning the validity of vaccines is something a group of researchers reflected on in May and June 2020 and was published in the journal PNAS (Proceedings of the National Academy of Sciences). Using models, they were able to establish that the mutations would not prevent viruses from being neutralized by the antibodies that organisms generate after receiving the vaccine. The next few weeks will be decisive in determining the strategy to be adopted: if the effectiveness of vaccine formulas decreases sufficiently, updating technologies or applying additional doses (boosters) could become imperative.

The history of the flu

It is not encouraging to observe that the vaccines that are applied around the world could lose their effectiveness in the face of new variants. However, the good news is that updating a formula is more common than you might think. “The flu is updated every year. The vaccine used for its production is very similar to that used by Sinopharm for Covid; with the virus inactivated strategy. The reason for its continuous modification is that the virus that causes it changes and adapts very quickly. New strains appear all the time that affect different territories, ”explains Lozano. Then he continues his reasoning: “In fact, the WHO detects which are the majority strains in the different continents and, on this basis, defines the mixture of inactivated viruses which will constitute the active substance of the vaccine during that year. ” To modify the vaccine, what the scientific teams are doing is cultivating the new variant – which did not exist before – and integrating it into the technology that they will distribute in a specific context.

For Hozbor, the flu example works like a antecedent. “It’s practically a pay-per-view vaccine. What circulates is analyzed, the viral strains that cause the disease are characterized and the immunogenicity is analyzed so that the one selected can generate cross-protection against other strains also widespread in a certain region ”, explains the researcher. Unlike what might happen with vaccines against the novel coronavirus, in the case of influenza, clinical trials are not necessary because there is experience accumulated over decades in analyzing protection against this virus. You just do animal testing to look at the neutralizing ability and then the strain is selected and the vaccine is produced which is administered annually.