Do mixed COVID-19 vaccines provide immunity?

The initial results of the CombivacS trial found that the antibody levels in individuals increased by 150 times when the Pfizer messenger ribonucleic acid (mRNA) vaccine was given after a first dose of the AstraZeneca severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, with only mild common side effects.


The AstraZeneca coronavirus disease 2019 (COVID-19) vaccine was suspended by several countries in the European Union following reports of blood clots leading to deaths in some people who had previously received the vaccine. The halt in AstraZeneca vaccinations has led many to question how they will complete vaccinations for people who have already received the first dose of this vaccine.

The Carlos III Health Institute, a research body under the Spanish government, conducted a clinical trial called CombivacS to evaluate the safety and efficacy of giving a second dose of an mRNA vaccine after the first dose of the AstraZeneca vaccine.

The trial was launched to support decisions for completing the vaccinations for those who have already received a first dose of the AstraZeneca vaccine. The study aimed to understand if enough antibodies were generated with a single dose or if a second booster dose is required.

The use of an mRNA vaccine combined with the AstraZeneca vaccine, the latter of which uses a chimpanzee adenovirus, may be beneficial because of the different technologies that are employed by these vaccines. To this end, both the AstraZeneca and mRNA vaccines have different mechanisms for eliciting the generation of antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus responsible for causing COVID-19. Moreover, the researchers were also interested in understanding whether a combination of these two vaccines could be highly potent in neutralizing the virus.

Preliminary results positive

The CombivacS trial is a Phase 2 clinical trial and was conducted in five hospitals across Spain starting in April of 2021. The study included a little over 600 participants below the age of 60 who had received one dose of the AstraZeneca vaccine at least eight weeks before the start of the trial.

The participants were randomly divided into two groups. One group of 441 people received the Pfizer mRNA vaccine, whereas the control group of 232 people did not receive a second vaccination. The antibody levels in the groups were evaluated after 14 days and follow-up will be continued for a year.

Recently, the trial's preliminary results were presented and demonstrated that a combination of the different vaccines, which is called a heterologous regimen, is highly effective in eliciting an immune response. In addition, there were no reports of adverse reactions upon using the combination. A heterologous vaccination strategy has been used for other vaccinations, such as for the Ebola virus.

An analysis of the antibodies in 663 people 14 days after a second dose of the Pfizer mRNA vaccine showed an increase of about 150 times in the antibody levels. The effect was already evident after a week, with the antibody increase being more than 100 times at this point. More specifically, the antibody titers increased from a median value of 58 to about 9,000. There was no change in the antibody levels of participants in the control group.

Flexibility in vaccinations

The trial also assessed the efficacy of the produced antibodies in neutralizing SARS-CoV-2. The researchers used a neutralization assay utilizing pseudoviruses with the SARS-CoV-2 spike protein. To this end, pseudovirus was incubated with the participants’ sera to evaluate the ability of the antibodies to inhibit infection by the virus.

These experiments demonstrated that the neutralizing antibody titers increased by more than seven times after patients received the second dose with the mRNA vaccine. Importantly, these antibody levels are higher as compared to those reported using two doses of the same vaccine.

There were also no serious side effects reported. Some mild side effects were reported, including headache, chills, mild nausea, cough, and fever, all of which were similar to those seen in other COVID-19 vaccinations.

These preliminary results indicate the possibility of mixing and matching different vaccines to combat COVID-19. Different countries in Europe like Germany, France, and Sweden are already recommending a combination of vaccines for people under the age of 60 who have previously received a dose of the AstraZeneca vaccine.

Another trial called Com-COV using vaccine combinations is underway in the United Kingdom. Preliminary results suggest a slight increase in the rates of common side effects of vaccination as compared to the side effects that are seen after individuals receive two doses of the same vaccine.

Given the short supply of vaccines faced by many countries, the limit of manufacturing capabilities, as well as the speed of production by certain manufacturers, using a combination of vaccines with different mechanisms and from different manufacturers will allow more flexibility in vaccination strategies for different countries.

Journal reference:
Lakshmi Supriya

Written by

Lakshmi Supriya

Lakshmi Supriya got her BSc in Industrial Chemistry from IIT Kharagpur (India) and a Ph.D. in Polymer Science and Engineering from Virginia Tech (USA).


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