US researchers have created a universal flu vaccine candidate using the same technology behind the Pfizer/BioNTech and Moderna coronavirus vaccines. Candidate because they only tested it in mice. And it’s universal because it protects against 20 subtypes of the virus. While those that affect humans are much less common, the rest circulate among other mammals and birds. An outbreak of one of these animal flu, which could be combined with human flu, could turn into an epidemic, as evidenced by the revelations of the last century.
A new flu vaccine comes out every year, last year’s immunity does nothing. Much of the blame lies in a protein called hemagglutinin. Influenza in humans is caused by type A and type B influenza viruses. Both can be classified as subtypes. For example, influenza A H1N1 and H3N2 circulate among humans. H denotes hemagglutinin (18 different versions) and N denotes another molecule, neuraminidase (there are 11 versions), which is also found on the viral surface. Meanwhile, only two different versions of hemagglutinin are known of the type B influenza virus. As with focused coronavirus vaccines the spicule S he used to sneak into the cell, hemagglutinin is the key target. Current vaccines and most vaccine candidates target H. pylori. The problem is that on the one hand it is unknown which subtype will enter the circulation next winter, and on the other hand, the high mutation rate of the tip, the head, eludes attempts to obtain a universal vaccine. For this reason, Recent efforts have been directed towards the body of hemagglutinin.it mutates less often and tends to be very similar between different subtypes.
What a group of researchers from the University of Pennsylvania (USA) is doing is betting against all subspecies of influenza viruses at once. To do this, they relied on messenger RNA technology already used by two of the most successful vaccines against the coronavirus. In essence, this technique inserts genetic instructions into nanospheres thus it is the host cell itself that produces hemagglutinin, which itself has no viral load. They obtained 20 vaccines together in this way. They tested each nanocapsule individually to ensure its effectiveness before combining them all into one formulation. The next thing was to test it on several groups of mice in the hope that they would all retain their capacity without cross-reactivity. This is the first time mRNA has been used to search for a universal vaccine candidate.
It would be difficult to make a vaccine like ours using conventional platforms because you would have to produce twenty different recombinant proteins, purify them and add an adjuvant to them.”
Claudia Arevalo, a virologist and first author of the study at the University of Pennsylvania and now at Pfizer
Bolivian virologist Claudia Arévalo, first author of the study, explains that this approach would be impossible using more traditional platforms, such as those that use viral proteins to design current vaccines: “It would be necessary to produce, purify twenty different recombinant proteins, and add an adjuvant. This would be a very expensive and laborious endeavor. ” Regarding the other more classical option, using inactivated viruses, he says, “it will present further challenges, such as isolating strains and successfully spreading them.” The strains we include are all known flu subtypes, meaning that some have pandemic potential and others have not yet crossed animal reservoirs. so you can imagine the difficulties of isolating and propagating viruses like this one.” At the University of Pennsylvania, where Arévalo completed his education Katalin Kariko and Drew Weissman They designed to take advantage of messenger RNA to introduce genetic instructions into cells.
Experiments with newly published mice in the prestigious magazine Scienceshowed that the rodents produced antibodies against all 20 flu, and that vaccination took at least four months. In the second part of the study, 28 days after vaccination, the scientists infected several groups of these animals with two different subtypes of influenza A; one of them looks like the influenza virus H1N1, which is predominant among humans. All mice in the control group, who were injected with a placebo instead of the vaccine formulation, died. However, those who were actually vaccinated and exposed to the homologous virus did not die or even lose weight. No viral load was detected in the lungs either. Meanwhile, those vaccinated and exposed to the strangest virus all fell ill, lost weight, but after seven or eight days the majority had recovered and only 20% had died. For the authors, these results mean two things: They do not sterilize vaccines, meaning they do not protect against infection, but protect against the toughest version of the disease, even viral variants that kill the antigen, as with coronavirus vaccines. Does not include vaccine.
“Current flu vaccines do not protect against pandemic flu viruses; If this vaccine works in humans, it does.”
Adolfo García-Sastre, Director of the Institute for Global Health and Emerging Pathogens at Mount Sinai Hospital in New York
“Current flu vaccines do not protect against pandemic flu viruses; “If this vaccine works well in humans, it can achieve that,” Adolfo García-Sastre, director of the Institute for Global Health and Emerging Pathogens at Mount Sinai Hospital in New York, told SMC. Spanish platform. “Current flu vaccines do not protect against pandemic flu viruses; If this vaccine works in humans, it could do that,” adds Sastre, quickly recalling that the study was done in mice. “The studies are in preclinical, experimental models. “While they are very promising and show the ability to protect against all subtypes of influenza viruses, we cannot be sure of that until clinical trials are conducted on volunteers,” he recalls.
According to Raúl Ortiz de Lejarazu y Leonardo, professor of microbiology and emeritus director of the Valladolid National Influenza Center, the most relevant aspect of this research is “from different subtypes of hemagglutinin (all existing ones, bats) rather than going to conserved regions of one or a few antigens”. It didn’t seem possible with platforms, but “current messenger RNA vaccine platforms allow the incorporation of many mRNAs to induce many different proteins, providing a multivalent and broad response that was not previously easy to achieve with protein platforms,” he concludes.
Víctor Jiménez Cid, professor of microbiology and parasitology at Complutense University’s School of Pharmacy, highlights why the idea of 20 vaccines in one is important: “Seasonal influenza A viruses circulating in the human population are just H1N1 and H3N2. Why should we include other H antigenic types in the vaccine? First, A viruses are zoonotic and although other species do not circulate in the human population, they circulate in other animals, such as H5, H7, and H9 types in birds. This means that if one of these species becomes infected with a disease, new pandemic viruses can emerge. antigenic splash It produces a new virus A that combines the genes of animal viruses with the genes of viruses circulating in humans”, he explained to SMC. The idea is unlikely, in fact this is what has happened in the four major pandemics of the last 100 years: from 2009The 1968 flu was then called the Hong Kong flu, the 1957 Asian flu, or the 1918 flu. combination of human and bird flu would have killed 50 to 100 million people a few years ago.
As for the keys to the vaccine’s efficacy, virologist Arévalo concludes: “This candidate is so successful because it contains multiple weapons of the immune system. Our vaccine, in particular, elicit different types of antibodies with diverse functions. It also generates different types of T-cell responses. [que eliminan las células infectadas y activan macrófagos]. As with all scientific studies, we need to do more research to determine the exact mechanism of our vaccine’s success.” Arevalo wanted to note that his views do not represent those of the University of Pennsylvania or Pfizer.
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