Sheltered in the valley of the river Brugent, on the edge of a regional road in the municipality of Amer, in Girona, one of the Spanish vaccines against covid is discreetly cooked. It is the most advanced in the race to achieve a preparation against the virus with the Spanish seal. The vaccine from the Catalan pharmaceutical company Hipra has already taken the first steps in clinical trials with humans and faces the second phase of the study with the recruitment of a thousand volunteers to verify the safety and efficacy of the drug as a booster dose. Preclinical tests with animal models and the first phase of the human trial have yielded “very promising results,” says Laura Ferrer, senior manager R&D (research and development) of human health of the company. If the data is favorable in this phase and the one that follows, the vaccine could be on the market in the second quarter of 2022.
The pharmaceutical company Hipra, specialized in animal immunology, made the leap to human health in the spring of 2020, when the coronavirus collapsed hospitals and turned half the world upside down. From the white coats, not from the dispatches, the idea of launching into the race for a vaccine against covid arose for the first time, explains now Elia Torroella, vice president of Hipra and director of R&D and Registers of the company: the scientists of the house, hardened in the creation and manufacture of animal vaccines, had the experience, the operational shot and the means at hand. You just had to try. “The move to human health was very gradual. We knew how to come up with a vaccine for coronavirus. In fact, we have vaccines for coronavirus because this virus also affects animals and it is a type of vaccine that we know. And we said: why don’t we do a proof of concept? That’s where it all started ”, recalls Torroella.
Escorted by a wheel of glass-enclosed offices, in the heart of the company’s headquarters in Amer, stands one of Hipra’s operations centers: the R&D laboratories, where the first ideas are born. A dozen technicians, dressed in white coats, gloves and goggles, manipulate machines and test tubes, take quick notes and review graphs on computers. Just over a year ago, right there, the recombinant protein vaccine that aspires to be the first against covid developed in Spain took its first steps. The World Health Organization (WHO) counts more than 300 candidates to be immunized against the coronavirus in research in the world: 135 in clinical development (with tests in humans) and 194 in preclinical phases. About half a dozen are Spanish.
“This vaccine is based on a part of the virus’ S protein, which is what it uses to enter the cells of the body,” explains Ferrer. This protein is completed with an adjuvant widely used in humans, “for example, in vaccines for influenza for the elderly,” the specialist intervenes. “The recombinant protein is not sufficiently immunogenic, it does not arouse the attraction of the immune system in a sufficient way for the organism to create defenses against this pathogen. The adjuvants attract the attention of the immune system so that it realizes that we are administering something to which we want to generate an immune response ”, he explains.
Hipra’s technology is different from that used in Pfizer and Moderna vaccines (messenger RNA), but similar to others, such as Novavax, which awaits authorization from the European Medicines Agency (EMA). for its commercialization: “What we are administering is a part of the virus and it is complemented with an adjuvant that what it does is to enhance the immune response”, explains Ferrer. “After being injected, our body responds by generating an immune response, both from antibodies and memory cells. If later we come into contact with the virus, our body will be able to fight it with these antibodies and memory cells ”, he details.
There is no microchip or trace of other anti-vaccine conspiracy theories in Hipra’s labs. “All that would be very expensive,” jokes the head of human health R&D. Although he immediately hardens his gesture: “The vaccine is safe. It has been confirmed in clinical trials. A very thorough safety assessment is made. What we have verified is that it generates a good response, but also with a good safety profile ”. The follow-up of the volunteers after the trials lasts about a year. Torroella insists: “At a safety level, when a vaccine is developed, it is done carefully and with a lot of knowledge behind it. First tests are carried out in different animal species, tests are carried out, forcing the conditions to take this vaccine to the limit and ensure that in no case will there be unwanted effects. When it comes to an authorization of the vaccine, you have enough data to guarantee this safety. But, in addition, when the vaccine is developed, there are control methods in each batch that is produced to guarantee that it meets safety and efficacy criteria ”.
In August, Hipra began human trials to compare the drug’s effects with other licensed vaccines. A first group of people who had not received any injection against covid or had had the disease were recruited and were given two doses three weeks apart to validate, above all, the safety and tolerability of the vaccine (the most appropriate concentration), as well as its immunogenicity —the ability to induce an immune response— and efficacy as secondary objectives, the Spanish Medicines Agency (Aemps) explained then. The first results, Ferrer assures, have been “very good”: “They have confirmed what we had seen in the preclinical phase: it is capable of offering a very good response to the different variants of concern. [alpha, beta, gamma y delta, las que tienen más riesgo de transmisión, virulencia o escape vacunal, según las autoridades sanitarias] and the forecast we have is that it be a vaccine with a broad spectrum of protection against the disease without any type of problem ”. Adverse effects, Aemps noted, are “the expected reactions of any vaccine.” According to Ferrer, “very moderate pain at the point of inoculation”.
With the first results in hand, Aemps gave the green light, just over two weeks ago, to the second phase of the trial (II-B), in which the efficacy of the vaccine as a booster dose will be tested. A dozen Spanish hospitals participate in the recruitment of more than a thousand people over 18 years of age, with a complete vaccination schedule with the Pfizer vaccine and who have not been infected by SARS-CoV-2. Ferrer is confident in the good results of the trial and aims to enter the last phase of the studies (phase III, with a much larger number of volunteers) in the first quarter of 2022.
Unlike messenger RNA vaccines, which require complex storage conditions – at ultra-cold temperatures, around 70 degrees below zero – Hipra’s drug can be stored in conventional refrigerators, which would facilitate its maintenance and transport, especially in countries with fewer resources. On the other hand, and with the threat of the new omicron variant on the table, which experts fear is more transmissible, virulent or escapes vaccines, Ferrer highlights “the versatility” of his serum: “It is perfectly adaptable to new variants if the need arises. We are confident that our vaccine will be able to protect against this omicron variant. But, if there is no obvious protection or we consider that it is not enough, our platform is adapted to make a change in a short space of time ”. Company president David Nogareda said last week that he could tailor his vaccine against the new variant in four months.
The Hospital Clínic de Barcelona, one of the centers participating in the trial, has already begun to inject the booster doses to the volunteers. The head of Infectious Diseases, Álex Soriano, celebrates the good results of the vaccine and points out the need for new serums to strengthen immunity and combat variants that appear. “It seems that the vaccination will not end and we will need to vaccinate more. Production will once again be a limiting element and we have already experienced that ”, he points out. The more drugs the better. And that of Hipra, he assures, “if the preliminary results are confirmed, it could become part of the arsenal of vaccines that exist.”
For now, the company has already started to pack the first doses. You have to start producing with time, says Torroella. In the bioreactors, a kind of boxes painted in colors on the wall of the R&D laboratory, industrial scaling has already been carried out, a key phase to “bring this vaccine to smaller volumes with which we work in R&D. to the production plant ”, says the vice president of the company. It is not the same, he exemplifies, manufacturing 600 milliliters as 500 liters of the drug. “If you do not scale well, you can lose efficacy or safety,” he insists.
At Amer’s main plant, a few meters from the R&D laboratory, a division for packaging and conditioning of other animal health products manufactured by the company is operating at full capacity. On one side of the warehouse, locked in an isolated room, a couple of workers dressed in personal protective equipment such as those worn by the pandemic toilets supervise the route of hundreds of vials that travel through the packaging circuit: a large reactor pumps the product to dispensers that inject the exact amount into each container. Closed and sealed, the vials travel in large boxes along a few lanes to the conditioning area, where they are kept in a large mechanized warehouse until it is time to label and package them. Dozens of operators monitor every step, from cartoning and inserting the leaflet to laminating.
The covid vaccine is packaged in another factory that the company jealously guards. It does not allow access. “In October we have already started to make industrial batches to be prepared so that, when they authorize us, we have enough vaccines to administer,” says Torroella. They have not yet begun to prepare – labeling and packaging – but the operators are already doing a training with water vials to have everything ready when mass manufacturing starts. The company has signed an agreement for 50 million doses with Vietnam and maintains contacts with other countries, confirms Torroella. Hipra anticipates that it will be able to produce 600 million doses in 2022 and double this number by 2023.
George Holan is chief editor at Plainsmen Post and has articles published in many notable publications in the last decade.