For some time, but especially in recent days, the possibility of modifying the immunization schedule of vaccines against COVID-19 has been suggested, so that the 3-4 week interval between the first and second doses is noticeably extended, perhaps up to 12 weeks or more. And thus prioritize vaccinating with the first dose as many people as possible.
There is no doubt that giving the first dose to more people, instead of using the vials available to complete the regimen to people who have already received the first dose, would accelerate the number of people immunized, at least partially, in an environment of vaccine shortage . The question is: does this make sense from an immunological point of view?
Why do we need two doses?
When the cells of the immune system recognize the antigen for the first time, the response is slow, poorly refined, and inefficient. This is what is called the primary response. And it implies that, if the pathogen is very virulent, our immune system is unable to control the infection with just that exposure.
The situation changes completely if we come into contact with the same antigen a second time. In that case, this secondary response is much faster, much more powerful, and ultimately much more effective, so the chances of surviving highly virulent pathogens are very high.
What works such a marvel? Well, memory cells, long-lived cells generated as the terminal element of a specific response, and that store the information on how to respond quickly and powerfully.
When we vaccinate, the ultimate goal is precisely to produce these memory cells, which will be our lifeline in case of infection. The point is that generating a sufficient number of memory cells usually, but not always, requires two or three injections of the vaccine, depending on the immunogenicity of the antigen with which we are going to vaccinate.
Why has the idea of delaying the second dose been suggested?
The clinical trials that have been carried out, and based on which the three vaccines approved in the European Union have obtained their license, require two doses spaced apart within a period of three weeks (Modern) or four weeks. (Pfizer-BioNTech; Astra-Zeneca).
The point is that we do not have reliable data on the effectiveness of these if they are administered differently. And yet the idea of deferring the second dose has been suggested from various circles.
There are two facts that have fueled this controversy. First, the UK regulatory authority’s decision to allow the administration of the second dose of the vaccine for Astra-Zeneca up to a maximum of 12 weeks after the first. Secondly, the data that comes from Israel, the country that is probably the most advanced in its mass vaccination campaign.
Israeli scientists have found that those who suffer an infection 12 days after receiving the first dose of the vaccine Pfizer-BioNTech they have a substantially lower viral load than the unvaccinated infected. This would assume (although they do not study it) that the disease would have a more benign clinical course.
In a second study, perhaps the one that has been used the most to justify this measure, it is shown that the single dose led to a reduction of up to 75% in the number of infected.
Finally, two Canadian epidemiologists suggested in the journal New England Journal of Medicine the administration of a single dose of the vaccine Pfizer-BioNTech until all risk groups are immunized, as their interpretation of the clinical trial data holds that up to 92% immunization would be achieved 12 days after the first dose was administered. Therefore, there would be data to support this possibility.
It is not so simple
But, as always, things are not as simple as they appear. Some key facts have been overlooked in the debate. First of all, and with regard to the data for the Oxford-Astra-Zeneca vaccine, we know that there were inconsistencies and errors during the development of the clinical trials of this vaccine.
For this reason, while in the United Kingdom the vaccine is being administered to the entire population and with a schedule of up to 12 weeks between doses, the European Union has decided to restrict the age range at which the vaccine is administered (in Spain in this time, those under 55 years) and maintain the four-week schedule. Perhaps we can resolve these concerns as vaccination in the UK progresses and we have new, more accurate data.
Second, the Israeli study that suggests a 75% reduction in infections is not carried out in the general population, but rather collects data from vaccinated personnel from the Sheba Medical Centre, a huge hospital with almost 10,000 workers, and therefore belonging to a relatively young age group. Therefore, we cannot extrapolate these results to the general population, and especially to the elderly in whom we know that the immune response is substantially weaker than that observed in the young.
Finally, the letter from the two Canadian epidemiologists supporting the delay in the administration of the first dose is answered, in the same issue of the journal, by three others that do not make the same interpretation of the data and that, therefore, they do not support modifying the guideline.
Then what do we do?
In my opinion, the data that we have so far do not support or justify a change in criteria over that approved by the European Medicines Agency. We must remember, once again, that the severity of the clinical presentation correlates with age, and to date there are no data disaggregated by this variant that are sufficiently robust.
Due to the greater weakness of the immune response of the elderly, already clearly evidenced in clinical trials, it is possible that this group did not achieve a sufficient level of immune protection if vaccination is restricted to one dose or if administration is deferred excessively of the second.
What is worse, this incomplete control of the infection could favor the development of new variants of the virus. A chronic infection could cause the escape of those variants capable of resisting a weak immune response, which might make the virus more virulent and lethal. Just the last thing we need.
In my opinion, the approval within a few days of the Johnson and Johnson vaccines (manufactured by its European subsidiary Janssen) as well as that of the German CureVac it will cause the vaccine supply to increase significantly in the short term. And we must focus on reaching the goal of fully protecting the most susceptible population, the oldest, as soon as possible.
These considerations, together with the absence of solid clinical data to support this, mean that the change in the administration regimen is not considered adequate from the immunological point of view. I believe that, at this point, the risks outweigh the benefits.
Professor of Immunology, Center for Biomedical Research, University of Granada. ” data-voc-vtm-id=”in-text-traffic” target=”_blank”>The Conversation ES.