Countdown to the first Spanish vaccine against Covid from the heart of Hipra

In a peaceful valley, halfway between the Girona counties of La Selva and La Garrotxa, the Catalan pharmaceutical company Hipra finalizes the cooking of its star dish: the first Spanish vaccine against the coronavirus. Oblivious to the commotion caused by the imminent arrival of the immunogen, which is expected to be approved in May and could be on the market next summer, the company’s hundred professionals who have made the gestation and testing of the preparation possible are excited from a first-timer to the long-awaited delivery.

Tense calm, nerves and suppressed emotion in Hipra’s heart. At the company’s Research and Development (R&D) plant, located on the main avenue of Amer (Gerona), where it is now

One year the seed was planted that has given fruit to the vaccine, one breathes apparent normality. Nothing suggests that are on the brink of celebration. The company has thought of three names for its creature and protects them with zeal. “We hope that it will be one of those that we will propose, although we do not have the last word on the matter,” they point out from Hipra. Dressed in white coats, protective goggles and gloves, the same technicians from the Research and Development (R&D) plant who supervised the first steps of the serum a year ago are now carefully preparing the final plating.

will come this summer

The recombinant protein vaccine that Hipra will supply to the European market this summer is nearing its debut, backed by very good results, both in the preclinical phase with animals and in human trials. The last phase (still underway), which is expected to demonstrate the safety and tolerability of the vaccine as a booster dose in a sample of 3,000 volunteers, was authorized last February by the Spanish Agency for Medicines and Health Products (
AEMPS) and is the prelude to its final approval by the European regulatory body. “Our experience in zoonotic diseases, our production capacity and the team we form make us face this final stage with the utmost enthusiasm and confidence,” he says. Laura Ferrer, Senior Human Health R&D Manager at Hipra. Hand in hand with him, this newspaper covers the main locations of the ‘making-of’ of the vaccine, which will be approved with a booster dose record but without giving up, as he clarifies, the indication of primary vaccination. “There are developing countries where the vaccine has not yet reached,” says Ferrer.

Crucial stop along the way

Two years after the most critical phase of the health crisis that paralyzed the world, in the heart of Hipra, the R&D plant where the first sketches of the vaccine were outlined, the company’s head of Human Health research recalls the most important moments that have marked the journey to reach the serum. “When we were surprised by the pandemic, we offered the hospitals in the area all the diagnostic capacity of the company. We put at your service our potential to perform PCR tests », she points out. Having overcome that point in the emergency, the Catalan pharmacist wondered why not go one step further and take advantage of its background in animal immunization to make the leap to human health and plant face esal SARS-CoV-2 with its own preparation. It was at the beginning of the spring of 2021, a year after the great collapse but with hospitals still in check due to the jolts of the virus, when Hipra launched the race for a vaccine against Covid-19.

“Before, we carried out several proofs of concept to check the safety and efficacy of different vaccine formulas,” explains Laura Ferrer. This previous experimentation was the starting point towards the vaccine that the
European Medicines Agency (the EMA) is about to bless.

Ferrer explains how it has been developed, what steps have been followed in the serum manufacturing chain, from the preparation of the initial cell culture that gives rise to the antigen to the final packaging. “The first step is the cultivation phase. The culture, made up of cells that produce or express the antigen or protein that we want to achieve, is fermented in it,” the company’s head of Human Health Research tells ABC.

In a small room with colorful bioreactors overflowing with cables and connectors, one of the plant’s technicians checks the crop charts on the computer screen. “Here the initial culture that will give rise to the vaccine is fermented,” he explains to this medium. A few meters below this glassed-in room is the enclosure where the fermented culture is purified. It is made through several processes and the objective is to obtain an antigen of high purity and quality. One of the techniques used by the company is chromatography, that allows the separation, identification and determination of chemical components in complex mixtures.

With the antigen already purified and optimized, it is passed to the elaboration phase. There it is mixed with the adjuvant to enhance the effect of the immune system and the processing is closed. “The recombinant protein is not sufficiently immunogenic, so we add an adjuvant that we create ourselves,” explains Ferrer.

The last phase is packaging, where the whey is finally divided into vials and packaged for sale. “Right now we are producing antigen stock. We have everything ready to start production when they give us the final authorization,” says the Hipra expert. She also clarifies that in the R&D headquarters where we are, the productions are on a small scale and that the large-scale production is carried out in other facilities. Although there have been no major obstacles on the road to a vaccine, the company acknowledges that it has had to face difficult decisions. One of them, perhaps the most decisive, was to make a stop along the way and open their product (very much aimed at the original Wuhan strain) to new variants.

“It was a difficult decision that we made a year ago with associated risks because that meant delaying the trials for a few months, although over time we have seen that it was correct and marked the destiny of our product for the better,” says the head of R&D at Hipra Human Health.

Adaptation to variants

In fact, one of the great strengths of the Spanish vaccine is its rapid ability to adapt to possible new variants. Added to this is its safety (it uses known technology), and good storage conditions (between 2 and 8 degrees Celsius), which allows the immunogen to be stored in conventional refrigerators without having to resort to a freezing process at 70 degrees below zero. as is the case with other vaccines on the market.

The great production capacity of the company – backed by half a century of experience and highly competitive facilities – are another point in favor of the success of the ‘made in Spain’ whey. “We expect to produce about 50 million doses per month, about 600 million a year. That during 2022, because the idea is to increase that rate of production in the coming years, ”announces the directive. “Unlike other vaccines that are being used, our immunogen has a high cross-protection capacity. In four months it could adapt to new variants that appear », he specifies.

Another great advantage is that it uses known technology. Hipra’s is also different from that of messenger RNA-based vaccines (Pfizer or Moderna), since it directly injects a part of the virus’s S protein (the one it uses to penetrate the body’s cells) to which is added an adjuvant that has been used for more than twenty years for influenza vaccines. Human trials have shown that the Catalan vaccine is more than adequate in terms of immune response and is also safe and versatile.

However, in the bowels of Hipra, among test tubes, microscopes, balances and test tubes the countdown to the long-awaited premiere of the vaccine lives with apparent serenity. They know that the cava will soon be uncorked, but they prefer not to celebrate their victory too soon. “There are reasons to be optimistic,” admit company officials. They recognize that it has not been an easy path but that a guardian angel has guided them through the most difficult moments. The countdown has been activated. They are eager to plate their most precious stew.

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