New truths and discoveries about vaccines against Covid-19: between efficacy and adverse effects

A new Australian study has demonstrated important differences in how AstraZeneca and Pfizer vaccines against Sars-Cov-2 affect the immune system. The researchers followed the immune responses of 102 adults of different ages, all living in South Australia, where there was no community transmission of Sars-Cov-2 at the time of the research. Participants had blood drawn immediately after each dose of the Oxford/AstraZeneca or Pfizer/BioNTech Covid-19 vaccines. They were also tested 28 days after each immunization to assess B- and T-lymphocyte activity.

We recall that while the Pfizer vaccine uses mRna technology to induce host cells to produce the Sars-cov-2 spike protein, the AstraZeneca vaccine uses a harmless virus (a chimpanzee adenovirus) to express the spike protein. In all cases, the immune responses induced immediately after vaccination were also observed to predict subsequent B- and T-cell responses to the vaccine measured 28 days later. After the first dose, it turned out that the Oxford/AstraZeneca vaccine elicits an unexpected memory response, as if it were not unknown to the immune system; it is a response that, in particular, is targeted against the adenoviral vector of the vaccine, not against the spike protein of Sars-Cov-2.

This is unexpected, because the vector is a chimpanzee virus, to which humans clearly cannot have been exposed before; but, despite the data previously obtained from the different groups that have developed this type of viral vectors, evidently the difference is not sufficient for the memory response established to face the common human adenoviruses, those responsible for forms of common cold in the population, to not be evoked . If this new study is confirmed in this aspect, it is an important limitation, precisely the one on the basis of which companies such as Reithera or Astra Zeneca had chosen to use vectors other than human ones (contrary to companies such as J&J or various Chinese or the Russians ): evidently, it was not enough to get away from human pathogens, and our immune system is still able to recognize some antigens.

It will therefore be important in general, and not just for this specific case, to know how solid the Australian data will be; certainly, this is a point to be thoroughly investigated. Furthermore, it has also been observed that the intensity of this sort of immune memory response against the Oxford/AstraZeneca product is related to the expression of proteins that act as a precursor of thrombosis or blood clotting; this means that the same mechanism identified could underlie the very rare effects of immune thrombotic thrombocytopenia induced by the Oxford/AstraZeneca vaccine and that of J&J. Confirming earlier data, the new Australian study also found that those who received just two doses of the Oxford/AstraZeneca vaccine generally produced lower amounts of antibodies and fewer of a specialized type of T cell that helps with antibody production, compared to those who had received two doses of the Pfizer/BioNTech vaccine; both effects were particularly evident in older people.

Very interestingly, both effects were corrected after a third booster dose of an mRna vaccine, illustrating how evidently the difference in efficacy of the different vaccines against Sars-cov-2 is also somehow linked to the nature of the technological platform used to induce the recognition of the antigen by our body. A further surprise for the researchers was the discovery that discomfort after a dose of the vaccine can actually be linked to its effectivenessa fact that agrees with the intuitive feeling of many people, but which up to now had not yet found such a clear confirmation as in this study.

In particular, people who showed symptoms of fatigue and fever soon after the third dose were more likely to have a better T lymphocyte-mediated response. Overall, this new study demonstrates that adenoviral vector-based technology has some limiting elements important, on which it will be necessary to work in the future, at least as regards the vaccines available today and certainly as regards the possible immunological memory against their vectors; at the same time, it is also very clear that also a single dose of an RNA vaccine, following different vaccines, allows for recovery of efficacypaving the way for the recovery of heterologous vaccinations useful and of equal efficacy to vaccinations based on RNA alone.

The more studies of this type we have available, the better prepared we will be to improve existing products; and it is for this reason that, even in a relatively calm phase from a pandemic point of view, we concentrate on extracting the maximum amount of information possible from samples already collected and in new types of studies. Provided, of course, that we don’t want to set aside vaccines and viruses, pretending that it no longer concerns us.