Clinical trials start for Spanish-made Covid vaccine: What we know so far

A FIRST phase of clinical trials for a Covid vaccine created entirely in Spain has been authorised, and if all goes according to plan, the formula could be in use by between January and March next year.

Scientists are working on the basis that the Spanish vaccine will be an annual booster jab, given that now the immunisation roll-out across Europe is very advanced, they would otherwise have very few volunteers to test it on.

In fact, in Spain, over 90% of the 40-plus age group has now been fully immunised, and more than half of those aged 30 to 39, with 61.1% of the population now inoculated and regional health authorities largely starting on the 20-somethings and teens, with a view to all students aged 12 and over having had at least their first dose by the start of the September term.

But the highly-contagious and much more aggressive nature of newer strains of the SARS-CoV-2 virus mean inoculation carried out to date may not provide sufficient protection – or not in those clinically compromised, at least – and Spanish health authorities firmly believe everyone will need annual booster jabs.

At present, no firm decision has been made on a third dose, but is strongly under consideration for the very elderly.

Phase one

The vaccine, developed for the pharmaceutical company Hipra, will be trialled using a random sample of volunteers, via a blind experiment – where participants do not know what they have been given.

Some will receive the new drug, and others will have an existing, already-authorised formula, but only the testers will know which.

This differs from a 'double-blind' trial, where those administering the drug do not know which they are giving, either; both types aim to avoid bias, such as a participant anticipating certain effects from the trialled medication and reporting symptoms or experiences that are not connected.

The aim of the first phase is to check the vaccine developed is safe and can be tolerated by those it is given to; phase two will study how far it is effective in terms of providing immunity.

Type of vaccine

The vaccines in use in Europe at present are the Janssen and AstraZeneca which, in simple terms, involve a deactivated viral particle introduced via a 'carrier', or vector; and the Pfizer and Moderna, which are RNA-messenger (RNAm) formulae.

Spain's creation is a PHH-1V, along the same lines as the Novavax and the Sanofi/GSK, which are currently being evaluated by the European Medicines Agency (EMA) with a view to being authorised for use in the European Union.

These use one of the proteins in the SARS-CoV-2 virus, the one referred to as the 'S-protein' because of its shape.

The difference between these and the PHH-1V is that the latter will use two 'S-proteins', one from the Alpha and one from the Beta strains – the former originally referred to as the 'British variant', but new mutations are now known by letters from the Greek alphabet so as not to 'stigmatise' the countries where they first appeared – and which 'lock' together when entering the system.

The next step

Now Spain's health authority has signed off the paperwork for the first phase of the trials, researchers will get to work right away – this coming Monday, they will start the volunteer selection process at Girona's Trueta Hospital and Barcelona's Hospital Clínic.

According to the Spanish Medicines and Healthcare Products Agency (AEMPS), the initial trials will be conducted on 'several dozen' volunteers aged 18 to 39 inclusive, who will receive two doses at 21 days apart.

This phase will take around a month and a half, after which phase two will branch out to other hospitals in Spain and also, possibly, in Portugal and Italy.

Volunteers will be split into groups, and the first group will be given the lowest dose of the Hipra vaccine.

They will be closely monitored for side effects or for Covid contagion before a final evaluation by an independent committee concerned with the vaccine's safety.

If no safety issues arise, the doses will very gradually increase, stage by stage and with the same stringent monitoring, as is 'habitual in these types of trials', according to national health authorities.

The dosage increases are aimed at finding the 'ideal' quantity – which produces as much immunity as possible with the fewest and most bearable side effects.

These effects are normally expected with vaccines, and shows the immune system is responding to the formula; Spain's health ministry has confirmed that younger and fitter people are more likely to experiences uncomfortable after-effects than older, less-fit persons, as the former's immune systems are more robust and will 'fight harder'.

Head of human health at Hipra, Dr Toni Maneu, says trials will include people who have not yet been vaccinated, to check safety, efficacy and effectiveness for the formula as a complete immunisation, with a view to its being distributed outside Europe and in countries where the inoculation roll-out is lagging behind.

However, it will largely be trialled on people who have either already had one or both doses of a different vaccine, or who have had Covid-19 within the past six months and are considered to have developed some immunity to it.

Given that only a small percentage of adults in Spain and Europe as a whole have not yet been summoned for their vaccine, the aim of the complete clinical trial is to find out whether the Hipra jab will be suitable for use as reinforcement or as a repeat annual immunisation.

Does it work against the Delta variant?

Initially referred to as the 'India strain', the 'Delta' is the SARS-CoV-2 mutation which is most worrying for international authorities at present, since it appears to be highly-contagious and aggressive.

Moreover, the Delta appears to be the dominant mutation in many countries at present.

It is not clear to what extent the existing EMA-approved vaccines protect against the Delta variant, and whether this level of protection is the same in everyone, or is lower in the elderly and in people with a weaker immune system.

Dr Maneu says the PHH-1V jab has 'been shown to be effective against all variants, including the India or Delta strain'.

This said, Spain's health ministry stresses: “We will need to wait until the full clinical trial is finished to be able to analyse all the data and draw conclusions.”

Hipra expects the new formula to be in use by early 2022 in a 'best-case scenario', or by late June next year 'in a more realistic scenario'.

It is set to mark a 'before and after' for Spain's pharmaceutical industry, which has a wealth of experience in developing and producing prescription drugs for humans and vaccines for animals, but is a relative newcomer on the human immunisation stage.