Just yesterday (15), when around 456 thousand doses of the Oxford/AstraZeneca vaccine landed in São Paulo, the state government announced that, then, this immunizing agent would be applied again as a second dose. It’s just that, two days earlier, the orientation had changed and it was to give Pfizer’s instead to those who needed to complete their vaccinations. It was like that, too, in other parts of the country.
Experts in the field call this a heterologous scheme — the combination of immunizers from different producers or even, as in the case of covid-19 here, from completely different platforms or technologies.
Now, the AstraZeneca vaccine, produced among us by Fiocruz, uses a viral vector, that is, a cold virus that usually infects monkeys, only modified to carry a small piece of Sars-CoV2 and present it to our immune system. It is a kind of Trojan horse, taking a sample of the coronavirus, made a gift from Greek. Pfizer’s vaccine, on the other hand, is based on messenger RNA, a molecule that sends a direct and straight message to our defenses, telling us what the enemy’s genetic identity would be.
The exchange of vaccines to complete the vaccination schedule, in principle, scared many people who went to a health center to receive the AstraZeneca injection, but saw the Pfizer injection in their arms. Would it hurt? Or would it work?
“You can understand the fear”, he says, with empathy, intensive care pediatrician Juarez Cunha, president of SBIm (Brazilian Society of Immunizations). And read the agreement term that people, often surprised, had to sign right there, at the vaccination post, before receiving the bite.
In it, the individual states that he agrees to complete his regimen with the Pfizer vaccine, despite having been started with a dose of AstraZeneca, “having carried out the risk and benefit assessment for the covid-19 vaccination”. Oops, who evaluated what?! Being aware of everything is necessary. And signing the consent form is fair, that is, as long as everyone knew, when they picked up the pen, what risks and what benefits they were talking about.
Rest assured: the heterologous scheme starting with an application of AstraZeneca and closing with another of Pfizer after the appropriate interval between doses does not hurt. And, more than that, it can work very well, as shown by studies presented at the recent XXIII National Immunization Journey, which took place last weekend, promoted by SBIm. In fact, it can even boost the immune response.
“The subject of heterologous schemes could not be missing from the event’s program”, says Juarez Cunha. “From the beginning, we already had the intuition that, sooner or later, they would be needed. After all, in a pandemic, there would always be a risk of shortage of doses of one or another immunizing agent.”
And, yes, it’s good to make it clear: until proven otherwise, mixing different immunizers is only valid when that vaccine that was applied in the first dose is missing. But if the duo AstraZeneca and Pfizer works so well, why not bet on it first, instead of taking two doses of just one of them? It’s a question that might cross your mind.
I went after the answer with Cristiana Toscano, an infectious disease specialist, an epidemiology specialist, who gave the lecture on the subject during the SBIm journey and who is the only Brazilian — in fact, the only South American — in the International Strategic Group of Experts in Vaccines (SAGE) of the WHO (World Health Organization).
waiting for more data
Professor at the Federal University of Goiás, Cristiana explains: “In fact, when someone takes AstraZeneca and then the second dose of a messenger RNA vaccine, such as Pfizer’s, looking at the levels of neutralizing antibodies, we notice that protection achieves 88%. It is, without a doubt, very promising. This scheme induces an equivalent or possibly even greater response than taking two doses of the messenger RNA vaccine.”
So, it appears to be an excellent choice. I mean, I don’t like to write “request” here because the expression refers to the idea of sommeliers of vaccines, who think they can ask for the immunizing agent they think is the most effective.
Here we go: first, no one can choose. Second, all vaccines are effective as long as everyone gets vaccinated—it’s as simple as that—making it harder for the virus to circulate. Third, as teacher Cristiana reminds us, knowledge of the effectiveness of heterologous schemes is still being built.
“We are working in a different situation, that is, without having an exact idea of what the correlate of protection would be,” she says. To understand this correlate, it is worth recapitulating that, in a disease like covid-19, the immune response that actually works to defeat the virus is one in which certain defense lymphocytes target the cells infected by it. Because, like any virus, Sars-CoV 2 spends most of its time inside a cell of the organism it has invaded. It just stays out of it, where it could be reached by the antibodies, the minute it leaves one to enter another.
There is, however, an apparent relationship between the amount of neutralizing antibodies and this cellular immunity, which is not easy to be measured in tests. Let’s say, then, that neutralizing antibody levels are an indirect way for you to deduce that your body is ready and that if it gets infected with Sars-CoV 2, cellular immunity is ready to go. But it remains to know the antibody levels that we need to reach with this heterologous scheme for this to happen.
“On the day we are sure that the effectiveness of this combination is really greater, we will be able to offer it right away in the first doses. But, while we acquire this knowledge, it is only adopted if a vaccine is really lacking,” says Cristiana. “Even because the risk of lack of vaccine may be greater if we do this “.
It has consistency. After all, studies on heterologous systems aim, above all, to make flexibility possible. In other words, in the absence of an immunizing agent, which one can I take? It is the opposite of “must be this and then this” strictly.
Let it be said that heterologous schemes are not an invention of the pandemic. They are recommended in other diseases — for example, when there is an outbreak of an infection and the same vaccine that was previously given in the population does not exist in that place.
better other than none
With more than 20 covid-19 vaccines available around the world—not counting the hundreds being tested—scientists are investigating every possible combination to address supply gaps. “That’s because it’s better for a person to take another vaccine than none at all. The worst of all worlds is when someone is too late or misses the second dose,” he warns.
Of course, the doctor is not referring to the Janssen vaccine, with a single dose, but to all the others. Well, not completing the primary vaccination schedule is giving a chance to bad luck. The virus that happens to infect this half-immunized individual will have the opportunity to train dribbles with the vaccine, generating variants that escape it.
“Besides, the person has the illusion of security and fails to take all precautions”, adds Cristiana Toscano. Before the delta variant, you don’t even need to take it easy. It passes easily and finds no obstacles in those who took just one dose of any vaccine.
what is known
Of all the possible combinations, AstraZeneca’s with Pfizer’s is by far the best known to date. Scientists ended up testing the pair under unusual conditions. That’s when, in the first half of this year, the suspicion arose that the AstraZeneca vaccine would cause a specific and very rare type of thrombosis — a tiny threat, but one that some countries have made a fuss about.
Then, when they recommended that this immunizing agent no longer be used by certain groups of the population, they had no choice but to apply the second dose of another vaccine to those who had already received AstraZeneca — and the one they had available was precisely that of messenger RNA. “It ended up being a natural experiment”, comments Cristiana Toscano. France, Dianamarca, Germany and Canada are examples of countries that adopted the heterologous scheme because of this.
With data that protection seems to increase with the second dose of Pfizer, some studies risked the opposite: starting with this vaccine and giving AstraZeneca later. “But the order seems to make a difference, because then the result was not so good”, says Cristiana Toscano.
Scientists now scour all the possibilities of heterologous regimens for the famous booster, the additional dose, months after someone has completed the primary regimen. “It may be necessary for anyone over 70 years old, especially if they took an inactivated virus vaccine in the past,” notes the doctor.
In this case, according to her, everything indicates that the combination of different vaccines works even more. And as the majority of the population here vaccinated for more than six months took CoronaVac, let’s await the studies, already in progress, which will show which is the perfect match.