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Combining vaccines. The Astrazeneca soap opera


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The Conversation

Ignacio López-Goñi

Full Professor of Microbiology of the University of Navarra

Today I start with the conclusion: if you are scheduled in a few weeks for the second dose of the vaccine, do not hesitate, and get the one you are told to get.. It is better to be vaccinated with a second dose of whatever it is than to be alone with the first dose. You have to be more afraid of the virus than of the vaccines.

That said, we begin. The general rule is that vaccines are not interchangeable and that this is only done in very exceptional cases. Some reasons for combining different vaccines may be that no more doses of the first vaccine are available or that the drug that was given first is unknown. They have to be vaccines that are licensed with the same dose for the same population and with the same antigen. The latter is not true in the case of the Oxford/AstraZeneca (now Vaxzevria) vaccine, which is based on adenovirus vectors, and the Pfizer/BioNTech (also called Comirnaty) messenger RNA vaccine, although both induce a response against the same S protein of the virus. For this reason, it is advisable in this case to carry out some clinical trials beforehand to check the effect of combining both formulations. It cannot be ruled out that the combination may provide a higher level of immunity and that it may be more durable.


In the UK they started a clinical essay (called Com-COV) a few months ago to test the effect of combining the two vaccines. The reason for this work was not the few cases of thrombosis that have been associated with the AstraZeneca vaccine (see Vaccine-induced immune thrombotic thrombocytopenia ) but to be prepared for a possible shortage of vaccine supply, which could be made up for by combining vaccines with different formulations.

Recently, The Lancet has published a preliminary result of this study. The definitive data is expected in June.

A total of 830 volunteers over 50 years of age participated. Four different groups were made according to the combination of the two doses: AstraZeneca+AstraZeneca, AstraZeneca+Pfizer, Pfizer+Pfizer, Pfizer+AstraZeneca. The effect of giving the second dose at 28 or 84 days after the first dose has also been tested. What has now been published are the results of reactogenicity, the mild adverse reactions that occur in the first 24-48 hours after vaccination. According to this publication, cases of fever, muscle or joint pain and generalized fatigue tripled among those who received a combination of Pfizer and AstraZeneca, compared to those who were vaccinated with the same formula both times. These side effects were not severe, were of short duration and were relieved with paracetamol. None required hospitalization. The essay continues to test the effect of the combination on antibody generation (called immunogenicity). A limitation of this study, which the authors themselves comment on, is that it has been carried out in people over 50 years of age and that the most serious side effects tend to occur in people under that age. Other studies have also begun, programs of study , in which the Moderna and Novavax vaccines are also being combined.


It is the Spanish essay , coordinated by the high school de Salud Carlos III. It is a very basic phase II study to test, as in Com-COV, reactogenicity (mild adverse reactions occurring in the first 24-48 hours after vaccination) and immunogenicity (generation of specific antibodies against the virus). It involved a total of 663 volunteers who had already received the first dose from AstraZeneca: 442 were given a second dose from Pfizer and the other 221 were given no second dose. The age range was between 18 and 59 years. The study is scheduled to last twelve months. They have now presented the preliminary results obtained two weeks after inoculation with the second dose. The only results of this study are that mild symptoms at 24-48 hours after the second dose are to be expected and that there is an increase in IgG antibodies against the neutralizing protein S of the virus. Both results were to be expected (there is always an increase in immune response after a second dose of any vaccine). Nothing more can be concluded from this essay. It is surprising that other control groups were not included, comparing for example AstraZeneca+AstraZeneca, AstraZeneca+Pfizer, Pfizer+Pfizer, Pfizer+AstraZeneca, as the essay Com-COV has done, and even with a single dose of both vaccines. This essay, therefore, does not endorse the second dose of Pfizer in those vaccinated with AstraZeneca.

If you really want to conclude something, EVERY experimental essay must ALWAYS have its own controls and it is not worth "using" the controls or results of other experiments.

In conclusion, both programs of study, Com-COV and CombiVacs, have so far only evaluated the mild side effects that appear 24-48 hours after vaccination and the production of neutralizing antibodies. They are not useful to evaluate those possible serious side effects that occur very leave frequently. For this, it would be best to look at the data provided by the United Kingdom, where they have already vaccinated about 6 million people with the second dose of AstraZeneca and have observed 6 cases of serious adverse effects, less than 1 per million vaccinated. Or simply follow the recommendation of the experts, the European Medicines Agency (EMA), the WHO or the report of seventeen scientific societies that continue to recommend giving the second dose of AstraZeneca.

AstraZeneca is still an effective and safe vaccine. The lousy management (also from business) and communication have generated a problem where there was none. Now, probably, we will donate in an altruistic and humanitarian way to other less developed countries the doses we have left over (irony).