The CombivacS study, which evaluates a combined vaccination schedule against him SARS-CoV-2 using a second dose of the vaccine of Pfizer / BioNtech (Comirnaty) in people under 60 years of age who have received a first dose of AstraZeneca (Vaxzevria), already has the first results of cellular immunity.
The data, published in an article in ‘preprint’ format in The Lancet, point towards an increased immune response against the virus, which adds to that already observed thanks to the generation of antibodies or humoral immunity.
The immune system reacts to vaccines with two forms of defense. The first is called humoral immunity and consists of the generation of antibodies by immune cells called B lymphocytes, which block the virus before it infects.
The data, published in an article in ‘preprint’ format in The Lancet, point to a greater immune response against the virus, in addition to the one already observed thanks to the generation of antibodies or humoral immunity
The second is cellular immunity, which occurs thanks to the activation of T lymphocytes, another type of immune cells that acquire the ability to destroy already infected cells. The generation of antibodies is the main objective of a vaccine, but also adding cellular immunity is very important to strengthen the immune response and improve protection against the virus.
Thus, the first figures from CombivacS show for the first time that a pattern of heterologous vaccination (based on the combination of different vaccines) induces a potent humoral and cellular response to the covid-19, data that, if confirmed over time, can facilitate the design of future vaccination guidelines based on their combination.
Experts point out that cellular immunity is not only enhanced after the second dose of a messenger RNA vaccine in people who had previously received a adenoviral vaccineInstead, based on data published by other research, it could be higher than that observed in vaccination regimens based on two doses of the same vaccine.
Increased IFN-gamma production
As explained Jordi Cano, a researcher at the National Center for Microbiology (CNM-ISCIII), the results reveal that the production of gamma interferon (IFN-gamma, a protein produced by T lymphocytes that helps trigger the cellular immune response) is significantly higher in the group of people vaccinated with the second dose of Pfizer compared to the control group, who only have the first dose by AstraZeneca.
The data support that, while the cellular response to SARS-CoV-2 does not vary after vaccination with two doses of AstraZeneca, vaccination with one dose of AstraZeneca and a second dose of Pfizer induces a four-fold increase in production. gamma interferon
Furthermore, although comparisons with other studies are complex due to factors such as sample size, study arms, and research time, this increase in cellular immunity after the second dose of a messenger RNA vaccine appears much greater than that observed in previous trials based on two doses of it.
The data from CombivacS conclude that, while the cellular response against SARS-CoV-2 does not vary after homologous vaccination with two doses of AstraZeneca, heterologous vaccination with one dose of AstraZeneca and a second dose of Pfizer induces a four-fold increase. superior in IFN-gamma production.
Three techniques to study antibody levels
The increase in antibody levels has been analyzed in the people participating in CombivacS using three different techniques. In all cases, it was shown that the use of a regimen based on the combination of two different vaccines enhanced the immune response: antibody titers multiplied by 150 times 14 days after the second dose of Pfizer was administered, an effect that it was already evident at 7 days.
Additionally, the efficacy of the antibodies generated by the heterologous vaccination was verified by functional tests, which made it possible to demonstrate that the antibodies produced were effective in protecting against SARS-CoV-2.
Specifically, antibody titers according to the technique that identifies the SARS-CoV-2 receptor binding region increased from a median of 58 to a value of 9,102, which represented a 150-fold increase in antibody titers in the group that received the second dose, compared to people who only received the first dose of AstraZeneca.
The second of the techniques used, which determines antibody levels based on the trimeric protein of the virus, confirmed the greater immune response: the people in the experimental group presented antibody levels before treatment of 82 units, which at 14 days reached a median of 3,430 units.
Finally, the third of the techniques explored the efficacy of the antibodies produced and showed a large increase in the neutralizing antibody titers after the administration of the Pfizer dose, an increase higher than that described with other vaccination regimens based on two doses of the same vaccine.
Alberto M. Borobia et al., On behalf of the CombiVacS study Group. ‘Reactogenicity and Immunogenicity of BNT162b2 in Subjects Having Received a First Dose of ChAdOx1s: Initial Results of a Randomised, Adaptive, Phase 2 Trial (CombiVacS)’. Pre-print The Lancet: https://ssrn.com/abstract=3854768
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