The office of Luis Enjuanes, one of the greatest experts on coronavirus in the world, does not have more than five square meters. On the second floor of the CSIC’s National Center for Biotechnology (CNB), in Tres Cantos (Madrid), he has a team of 16 people working in the laboratory on the other side of his door that has been searching for almost two years for a sterilizing vaccine against the coronavirus that prevents people from infecting and from getting infected.
If scientists don’t like something, it’s answering a question journalists love to ask: “When could it be finished (in this case, the vaccine)?” There are so many factors that influence the success of an investigation that predicting it often leads to errors. At first, his team thought he might have the medicine by this time. But the obstacles in the investigation have been delaying it. Now, “if everything goes well”, Enjuanes is given another year. “Fortunately, vaccines are no longer as urgent as at the beginning of the pandemic,” he says.
For yours to have value, Enjuanes assumes that it has to contribute some characteristic that existing ones lack. And the most valuable thing may be something that none of the current ones has achieved: sterilization, that those who receive it do not become infected or infect others. To achieve this they work with a nasal application. “If you prick it intramuscularly, whether in the arm, the thigh or the butt, it provides a systemic, internal immunity that lasts for 20, 40, 60 years and is very good with a single dose. However, it is not what we need now. Now we need an immunity that protects the mucous membranes ”, he reasons.
The problem with intranasal vaccines is that their approval is much more complicated. Regulatory entities subject them to strong security measures, as they fear that some component of the drug will cross the blood-brain barrier, which protects the brain from harmful substances, and cause unwanted side effects.
Rinses ensures that this possibility is minimal and that there are other medications that are applied through the nose without this result. But since it is not “the preferred method by health authorities”, they work on two versions of the vaccine with both types of application each: intranasal and muscular. “I am convinced that if they could administer the same Pfizer or Moderna vaccine intranasally, they would not need two doses. And the people who received it would not get the virus. And if it entered, they would not replicate it or transmit it to other people ”, he assures.
In the race to launch the first effective vaccines, these brands and a few others, such as AstraZeneca, won. Janssen, who arrived a little later, had to add a value that others did not have: it did not require extreme cold for its conservation and, in addition, it required (a priori) a single dose. Vaccines against covid will continue to evolve and adapt, providing improvements, but no longer with the urgency of stopping a pandemic in full explosion with the population without immunization.
There are more than 300 vaccines against the coronavirus under study. Of these, 135 have reached the clinical trial (with humans). Among the half dozen that are being investigated in Spain, only one has reached this stage: the one developed by the pharmaceutical company Hipra faces phase II-B of the clinical trial with the recruitment of a thousand volunteers to verify the safety and efficacy of the serum as a dose Of memory.
Enjuanes and his team aspire to test them in people early next year. “The first and the second [fases clínicas] they are economically very feasible even for our economies, our laboratory and our institution, the CSIC, because you can cover that with four or five million euros. But phase 3, which involves up to 60,000 people, is many millions. And you can only do that if you have the collaboration of an important company. We are in talks with one of those companies with a lot of scientific experience and great potential ”, underlines the researcher, who would be retired if it were not for the pandemic.
Three levels of security
The team uses the CNB facilities, which allows them to work in laboratories with three levels of security. The level 1 is distinguished by its yellow door. With little space of separation between the researchers who work constructing mutants of the coronavirus in which they eliminate genes that attenuate its virulence to thus construct future vaccines. On a plate, Enjuanes shows how the cells infected by the virus disappear and those that remain remain visible, a sign that there is an immune response.
The medium security lab has orange doors. In it, researchers work with microorganisms that would not have the capacity to infect humans even if they escaped. Despite this, to enter you have to go through a lock and put on a robe that does not leave the room.
And the jewel in the crown is the 3+ safety laboratory (there is only one more level in international standards, 4). The door is red, and looks more like that of a submarine. Before entering, a camera watches to monitor all movements: who enters and who leaves. Inside, dangerous pathogens are handled and the measures to prevent them from escaping are extreme.
First of all, the pressure is negative: when the door is opened the air enters, but does not come out. Everyone who accesses must wear airtight clothing through which they breathe through a filter: this is what differentiates them from level 4, which has an oxygen supply through a cylinder. Inside the laboratory, the air, in turn, is filtered. But there is one more security measure: inside the enclosure, which can only be accessed with express authorization, each researcher uses a cubicle isolated from the others.
“Here, for example, we do the evaluation of mice when we have subjected them to a lethal dose of the virus. If, for example, the mice that were vaccinated survive compared to the unvaccinated ones ”, explains Enjuanes at the gates of the enclosure.
At the moment, their preparation can only be used with animals. If the safety sample in the macaques is good, they will try to make the jump to the clinical phase. But they will have an arduous journey ahead of them: more than 85% of the drugs that reach phase 1 remain by the wayside. The good news is that vaccines against infectious diseases have a better prognosis: a third of those that get to experiments with humans end up being approved. The bad news is that most don’t.
George Holan is chief editor at Plainsmen Post and has articles published in many notable publications in the last decade.