Two months to know the future of the Catalan covid vaccine

BarcelonaIn October, at the latest in November, it will be known whether the Catalan vaccine against covid-19, promoted by the company Hipra, is safe and immunogenic, i.e. it does not cause serious side effects and stimulates the immune response. This week, the first doses of the PHH-1V vaccine (the name under which the Girona-based company has presented its prototype to the Ministry of Health) have begun to be inoculated and, so far, six people have already received it, three at the Josep Trueta Hospital in Girona and three at the Hospital Clínic in Barcelona. A fortnight ago, the Spanish Agency for Medicines and Health Products authorised Hipra to begin clinical trials in humans, and the researchers have decided to start with a sample of 30 people. Only if the promising pre-clinical results are confirmed on a small scale will it be possible to extend the study to hundreds of people, and even then it will be a year before the final conclusions of this first clinical step can be drawn. In practice, however, the results will be almost immediate: within two to three months there will be enough evidence for scientists and authorities to consider whether to continue or discontinue the study.

The main actor in this trial, as in any other that gets the authorisation to test its drug in humans, are volunteers. And, in this case, researchers have thanked this Friday the "great social response" of the population, since the pool of volunteers is higher than expected: more than 400 people have applied to participate, although only a few dozen have been selected at random. "It has not been difficult to recruit them", celebrates the specialist of the Infectious Diseases Service of the Hospital Clínic and principal investigator, Lorna Leal. "This interest indicates that the population wants to contribute to science to fight the pandemic", agrees Rafael Ramos, a researcher at the University Institute of Primary Care Research (IDIAP) Jordi Gol and the Institute of Biomedical Research of Girona Dr. Josep Trueta (IDIBGI).

However, as this is a phase 1 clinical trial, the researchers will initially only test the vaccine in a small group, specifically in 30 people, and the whole process will be thoroughly evaluated by an independent pharmacological surveillance committee. All volunteers must be healthy people between 18 and 39 years old with a naive immune system to covid, since they have not passed the virus and have not been vaccinated. "And if everything goes well, in the next phases we will be including hundreds of people and we will also progressively expand the criteria for participation, for example with vaccinated people who may need a booster [a third dose] or who have already had covid", says Leal.

The volunteers chosen to receive the first doses of Hipra have been informed of the study and their participation "in detail", the researchers stress. "We called them for a first visit and checked that they met the exclusion criteria. For example, some had passed the virus asymptomatically and did not know it, so they could not participate", explains Ramos. Once selected, 25 will be administered the first dose of the research vaccine and the remaining 5 will be inoculated with the control vaccine, which in this case is Pfizer because it has an identical regime (two doses 21 days apart). In addition, not all participants with the vaccine designed by Hipra will receive the same dose. "We start the trial with the lowest dose and, from this point on, three different doses that increase are proposed. Knowing which is the right dose is also part of this trial", explains Leal. Neither the volunteer nor the research team will know which vaccine has been administered in each case, a method known as a double-blind trial.

The PHH-1V vaccine has a different technology from the vaccines that have been used in Catalonia. While Pfizer's and Moderna's are messenger RNA and AstraZeneca's and Janssen's use a viral vector, Hipra's is a recombinant protein vaccine. It contains two proteins, one corresponding to the alpha variant and the other to the beta variant, which are joined together and form a unique structure called a dimer, which is accompanied by an oil-in-water emulsion (an adjuvant) like the one that has been used for more than 20 years in vaccines against influenza or human papillomavirus (HPV). "We are using a technology that we know and have experience with, and this also gives us confidence. This factor and the fact that it is kept in refrigerators at between 2 and 8 degrees are the main advantage of this vaccine", says Leal. And Ramos adds: "The recombinant protein makes it easier to adapt to possible new variants".

No marketing calendar

The head of the Infectious Diseases Service at Hospital Clínic, Àlex Soriano, has stressed that, given the predominance of the delta variant and the threat that other mutations may proliferate in the near future, it is necessary that the vaccination coverage reaches maximum levels, "above 90%". "That is why it is important to develop this vaccine, which is being done entirely in Catalan territory", he explained. The expert also stressed that having different vaccines available makes it possible to face other present or future challenges, such as revaccinations for immunocompromised people or those with a weak immune system, such as the elderly, or the immunisation of children under 12 years of age, which is not authorised at the moment.

However, there are still several unknowns surrounding this vaccine, which has just started the trial and the viability of which is not guaranteed, and that will only be solved with clinical trials. One of the unknowns now is whether more than two doses will be required to effectively protect against covid or whether it could be used as a booster for the Pfizer and Moderna vaccines. "The heterologous approach is not uncommon with these types of protein vaccines, but we don't know yet", Leal admits. Regarding the efficacy of the vaccines, the researchers say that the health authorities state all vaccines must have an efficacy of more than 50%.

The researchers also do not dare to estimate a commercialisation date. "The most important thing is to overcome each of the phases. Now we are starting the first phase and the goal is to continue to scale up", Soriano said. And even if the vaccine is shown to be safe and effective, the last word will be given by the health authorities, specifically the European Medicines Agency (EMA), which is the body that is authorising the use of vaccines against covid in Europe.

"It is a vaccine that will be produced in a private laboratory and that we are now testing so that it can be marketed and included in the range of vaccines available against covid", concluded the director of the IDIBGI, Marga Nadal. And on the possible price of marketing the biologist has recalled that this is not a variable that "is evaluated in clinical trials" and that, if everything evolves favorably and the relevant authorisations are received, this decision will be the manifacturer's responsibility, the Hipra Girona company.