The results of the CombivacS study indicate “a four-fold increase in cellular immune response” after inoculating Pfizer in a second dose
In studies with the AstraZeneca vaccine, it was found that the second dose did not potentiate the cellular response induced by the first.
In the case of cellular response, those responsible for CombivacS assure that the studies are comparable: “The technique is similar”
Four times stronger cellular response
In the preliminary study just published in The Lancet, those responsible for the trial explain that “while the cellular response to SARS-CoV-2 does not vary after homologous vaccination with two doses of AstraZeneca, heterologous vaccination with one dose of AstraZeneca and a second of Pfizer induces a four-fold increase in IFN-gamma production ”. What does this mean?
“When we have an infection, our immune system makes a coordinated, antibody and cellular response. Antibodies tell us that our system has reacted. The production of interferon (IFN) tells us that the cellular response works ”, he explains. José Alcamí, virologist at the ISCIII and one of those responsible for the Combivacs study. “Interferon it is a marker that the cellular immune system is responding, the one that indicates that the T lymphocytes have been activated against the virus ”.
And how do you know that the cellular response is “four times greater” in the group of people vaccinated with the second dose of Pfizer than in the group that has not received a second dose? “This We see it by measuring the production of that interferon-gamma. The T lymphocyte response is highly activated. It is going from 0 to 4. It is not just a quantitative change, but a qualitative one ”.
When he talks about “going from 0 to 4”, Alcamí refers to the increase in cellular response after a hypothetical second dose of AstraZeneca, which would be 0, and compares it with the one caused by Pfizer, which would be 4. Because When it comes to cellular response, the study authors do dare to compare this study with others. And they compare it with response seen in AstraZeneca’s own studies on your vaccine.
Comparable to AstraZeneca studies
“In vaccinations with AstraZeneca, with the second dose the T lymphocytes do not increase anything. They do not see that the second dose induces a cellular response, we do see it and it is also very consistent, a four-fold increase is important. And here the comparison is more admissible. Because We went from seeing nothing, no response, to doing something. It is an added value “, warns Alcamí.
When communicating the cellular results of the study, however, they themselves acknowledge that making the comparison is difficult. “Comparisons with other studies are complex due to factors such as sample size, study arms and research time ”. Y is the most critical criticism of this test, in fact, the lack of an AstraZeneca-AstraZeneca arm with which to compare the results of the AstraZeneca-Pfizer regimen.
Because the data provided by CombivacS on the combination of AstraZeneca and Pfizer is only compared with that of not putting anything. Namely, a second dose of Pfizer is compared with not giving a second dose, instead of comparing it with a second dose of the same vaccine.
“They are not telling you that you are more protected by combining vaccines than by giving the second dose of AstraZeneca. It has not been shown that putting the second dose of Pfizer is better ”, warned microbiologist Ignacio López Goñi, when talking about whether the immune response of the AstraZeneca-Pfizer combination was better or worse than the double dose of AstraZeneca. “Without a doubt it is an interesting question and it would be an important answer, but we do not have it,” Alcamí acknowledged at the time. “You cannot conclude that, because they are two different studies, the technique is not the same … Our results are not comparable ”, acknowledged the virologist.
Alcamí, however, now assures that in the case of cellular immunity, comparing Combivacs results with AstraZeneca studies is possible “because the techniques are not identical, but they are very comparable, in both cases it is about stimulating T lymphocytes and measuring interferon production. The strict comparison must always be done with great caution, but here the technique is very similar ”.
And when we look at those AstraZeneca studies that measured the immune response of that vaccine with the full schedule, we read: “A booster dose of the vaccine induced stronger antibody responses than a half dose booster dose, although the magnitude of T-cell responses did not increase with any of the booster doses ”. In other words, after the two doses of AstraZeneca, “the cellular response is maintained over time, regardless of the vaccination interval, age and gender ”, stand out from Combivacs.
Pending British study to confirm results
With all these data on the table, those responsible for Combivacs conclude: “Our study confirms robust humoral and cellular immune response after second dose of BNT162b2 (Pfizer) in individuals previously primed with ChAdOx1-S (AstraZeneca) between 8 and 12 weeks before ”.
Although they are also cautious and refer to other studies on combination of vaccines. Specifically, the one that is underway in the UK. “The Future studies comparing homologous versus heterologous vaccination schedules will help to better confirm and understand the humoral and cellular immune responses observed in this clinical trial ”.
The study of The UK does include an AstraZeneca-AstraZeneca branch, unlike Combivacs. Alcamí explains it, and alludes to “Ethical reasons” to justify not having tried that option. “Their study was raised in February, when the cases of thrombi with this vaccine had not yet been reported. Here, our study was authorized when we were in full stop of the vaccination with AstraZeneca ” while investigating what happened.