Not even the time to have created and have available vaccines innovative to Rna-messenger that is already thought and tried to produce the so-called “second generation vaccines”.
New variant vaccines
Let’s be clear, it is not that the ones we are using in the fight against Covid are to be thrown away but, on the contrary, they are the springboard to have the upgrade, a bit like when you buy a new smartphone just put on the market that needs updates that are issued by the parent company. With the new anti-Covid vaccines in which technology is fundamental we do more or less the same thing: the second generation it is already developed but further adjustments are needed. All this because the Sars-Cov-2 “runs” fast and changes just as fast. The main mutations are now under the eyes of all, the English, Brazilian and South African ones (we have dealt with them in this Focus) which, while changing their sequence only minimally, risk jeopardizing the efficacy of current vaccines developed in record time.
What happens and how to adapt them
One way to adapt existing vaccines to new mutations is to use a new one Rna messenger, that is, which contains the varied nucleotide sequences. Technically, the Spike protein of the virus is made up of two important portions, the S1 portion and the S2 portion. The S1 portion contains a region called Rbd (receptor binding domain) which is the key that serves to bind to the target cell by adhering to its receptor (lock) called Ace2. The S2 portion, once the door is opened, allows the virus to enter the cell. The mutations almost all affect Rbd, the outermost part of the protein. Fortunately for us, these new vaccines are flexible and easy to make changes.
“The same thing is done with the flu virus”
“Not only is it feasible, but in reality we are already implementing them because this is what we do for the flu: every year we corrects the vaccine when the virus changes and new variants develop. The previous year’s vaccine is either no longer good or, in any case, it’s not optimal. In this pandemic it seems that we are only realizing now that this virus can change, “he says exclusively for ilgiornale.it Prof. Massimo Clementi, Director of the Laboratory of Microbiology and Virology of theIrccs San Raffaele Hospital in Milan. However, Prof. tends to reassure everyone: vaccines work at present. “In South Africa it was said that the AstraZeneca vaccine is less effective on that variant but it has to be tested, all the other vaccines work. From a purely practical point of view we can be essentially calm, the variants that have been generated do not alter the response to the This does not mean that it is not necessary to improve and adapt the vaccines which, among other things, are built in a way that they can be adapted very easily, “says Clementi. Exactly as for the flu vaccine, therefore, those against Covid will adapt if it continues to change.
“Various ways to modify vaccines”
“Moderna has already said it is preparing a vaccine for the South African variant, there will be a modification that already is available. These RNA vaccines have the advantage that they can be easily modified, it is estimated that a relatively limited period is required to make these changes. In other cases, someone has suggested that three administrations could be done instead of two. There are various modalities “, said Prof. Silvio exclusively for us Garattini, pharmacologist and founder of the Mario Negri Institute of Pharmacological Research in Milan. The Italian scientist also reassures us about AstraZeneca, a non-RNA vaccine. “In the case of AstraZeneca it is about changing only one vector, an adenovirus that carries the RNA into the cells. It is enough to change the RNA to have responses against the modified proteins,” he points out. “The same is true for the Russian Sputnik vaccine – adds Clementi – But at the moment it is not needed because a work has been published on the efficacy of antibodies against all three variants”.
“Automatic adjustment”. Science and Medicine, in a complementary way, have catapulted us into a new world accelerated by the pandemic. We remind No-Vax friends that this new type of vaccine has been studied for many years, it did not appear suddenly. “Vaccines can be done modify, it is valid for all but for those with messenger Rna it is a trivial correction, it is very simple to change the sequence of Rna. The important thing is that the three phases that take a long time do not have to be repeated but, as with the flu virus vaccine, there is an automatic adjustment – Prof. Clementi tells us – the vaccine remains the same, it simply changes the sequence of the Spike region. “In short, with small corrections that incorporates a new code, we can neutralize both the variant and the Spike of the variant.
Single multi-combined vaccine?
At this point the question arises spontaneously: should a single multi-combined vaccine be developed, i.e. with more than one protein what happens with papilloma and pertussis vaccines? In the case of Covid, however, the answer is negative. “As much as we can combine multiple sequences and produce a vaccine against all the sequences that exist, there is always the possibility that the virus escapes by generating a variant that is not contained in that mixture,” Clementi tells us. The difference with papilloma viruses is that these are very stable, Covid instead is not because “totally unstable from a genetic point of view. We could do it but by reducing the activity a little: having 4 different proteins we would have for each single protein a lower potential than having just one, “he adds. It is the story of HIV and hepatitis C for which there are no vaccines that work but treatments with drugs. In the case of the pandemic, however, which spreads in a totally different way from other diseases, it is “essential to develop a vaccination, Covid will not be blocked if the entire population is not vaccinated. This is why we should go faster, otherwise the possibility for the virus to find other ways to resist. We must put it in a position where it will no longer be able to find an escape route “, concludes Clementi.
“What’s circulating?” Silvio Garattini is also on the same wavelength: the multi-combined vaccine is complicated because “you have to see how many variants have the upper hand”, he tells us, and it is not such a viable path. Meanwhile, the biggest need is to “do a continuous analysis of the virus that circulates: in Great Britain they have sequenced more than 130 thousand genomes, in Italy we have made a few thousand, we do not know what circulates, we have identified the variants but not how much they circulate, whether in a small area or if it is widespread throughout Italy . If we do not know this, we will not know what to do with neither first nor second generation vaccines – the scientist tells us – The need to have vaccines goes hand in hand with the need to know what really circulates.
“Caution, we don’t know what will happen”
“I think it is important that we try to hurry up and not give people the impression that we have solved the problem”: the scientist’s appeal is clear, we must not be lulled into the idea that the problem has been solved between vaccines and monoclonals, but we must rely on the rules of protection with masks, distancing, hand washing and avoiding crowded places. “Looking around it seems that this has become what a part of the population that behaves as if there is nothing, this aggravates the situation. We must be prepared, no one knows how the pandemic will develop in the future “. Prof. Garattini denounces above all the enormous delay in vaccination and it is essential that new ones arrive” for the current variants and those that may occur in the coming months. It is very difficult for herd immunity to be achieved before the end of the year and, if we look at the whole world, it will probably take much longer. The vaccine is not available for low-income countries, we need to prepare for this. “
“A different job is needed.” The idea is of to achieve a chain of factories ready to develop vaccines as and when they are needed, a European program for all producing more than what is done because “vaccination must be done everywhere, is what should reasonably be done”, he tells us. “We need to do a forecasting work that we have not done in the past by booking vaccines, we must avoid making the same mistakes again, let’s put ourselves in a position to fine-tune the things that are necessary following the most negative, most unfavorable scenario. they will develop variants that are more harmful, the better, “he concludes.
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