Which vaccine to choose after a first dose with AstraZeneca?

In Italy the freedom is left to decide which type of vaccine to receive after a first dose of Vaxzevria (Oxford-AstraZeneca). Here are some points to consider, between pros and cons, in choosing whether to continue with the same formulation or switch to mRna ones like Pfizer and Moderna

(Photo: Mika Baumeister / Unsplash)

We are facing the umpteenth matter of public debate regarding the branded Covid-19 vaccine Oxford-AstraZeneca. Prime Minister Mario Draghi he communicated the possibility, for people under 60 who have already received a first dose of the Anglo-Swedish vaccine Vaxzevria, to make a active choice on which formulation to receive in the second administration. Thus, the question of whether to continue with the same vaccine or to opt for one heterologous strategy a mixed vaccination has become prominent.

In practice, what to choose between the AstraZeneca + AstraZeneca combination and the AstraZeneca + mRna vaccine? Where the latter, in fact, today means opting for the formulation of Pfizer, although in general it could also be that of Modern as well as other vaccines that should arrive shortly on the market.

We immediately anticipate that, of course, there is no single answer. There is not in itself a better or a worse, a quite right is one mistaken, except in regards to the completion of vaccination: also receive the second dose it is essential to achieve a good level of protection against the disease, e any vaccine it’s better than a non-vaccine. Not surprisingly, the very idea of ​​granting this freedom of choice derives from the desire to bring as many people as possible to get vaccinated, convincing even those hesitant people who are perplexed by the idea of ​​changing the vaccine formulation between the first and second dose.

Here are some aspects to take into consideration before choosing, trying to stay away from unmotivated distrust, belly views e false myths.

The solidity of scientific data

In this case, between homologous and heterologous vaccination, at least for the moment, there is no comparison. Since administering a double dose of Vaxzevria is being studied by many months, while the vaccination mixed is an option only explored by a few weeks, the quantity and quality of the scientific evidence we have collected so far is very different. For the double dose of the AstraZeneca formulation we have behind us phase 3 studies which demonstrate the actual level of effectiveness, we have millions of doses administered only in our country (and many more abroad) and therefore a rather advanced solidity in terms of data on efficacy, immune response, adverse effects and any other relevant aspects. This despite the choices made by regulatory agencies and political decision-makers, national and not only, have seemed very much swinging.

For the vaccination heterologous, on the other hand, all that exist at the moment are essentially preliminary evidence: studies just initial and previous to phase 3, a rather small number of people involved in these trials, some preprint and little else. We are talking about studies that still have their own authority, and above all they seem to be all of them rather agree, but they are samples of dozens or at most hundreds of people taken into consideration. In short, nothing to do with the mammoth numbers we have available for the AstraZeneca double dose.

The effectiveness of vaccination

Given that scientific data has a different solidityHowever, it is true that at the moment the evidence seems to indicate that mixed vaccination has a protective effect well above the AstraZeneca double dose. In quantitative terms, there is talk of a difference in the induced immune response that comes to be even by a factor of 4.

Second a study in preprint (therefore not yet published and awaiting peer review) conducted in Germany, for example, three weeks after the administration of the second dose the heterologous strategy results in a greater number of antibodies, in a increased cellular immune response and in a higher quality of the antibodies themselves, which then translates into superior efficacy against both the original Sars-Cov-2 virus both against its variants. In quantitative terms, among the 87 people involved in the study, those who received a mixed vaccination have increased its own antibodies to 11 times thanks to the second dose, while those who have continued with AstraZeneca have only them tripled (a 2.9x increase, to be precise).

There are already two possible explanations on the table as to why mixed vaccination stimulates a stronger immune response. It is a question, at this stage, of simple ones reasonable assumptions, on which, however, the scientific evidence is still all in progress. The first explanation is that using two different vaccine platforms (a viral vector of type adenovirus before and a vaccine a mRna then) stimulate two arms different of the immune response, first that cell-mediated and then that antibody. Given that the overall protection from the Covid-19 depends on the sum of these two responses, the heterologous vaccination could therefore correspond to an immune response more varied and complete, therefore better. The other hypothesis, which is not alternative but complementary to the first, is that the second dose of AstraZeneca has the but tarpate because the immune system would activate one additional immune response against the adenoviral vector at the first dose, and consequently the second administration would come in part opposed by the immune system itself. This effect would instead be averted by mixed vaccination, which would therefore guarantee more effective protection.

Adverse Effects

This point, of course, is one of the most delicate. As is well known, it was the very rare serious adverse effects (le thrombosis) attributable to the formulation of AstraZeneca to induce the suspension of the official administration of the vaccine also for under 60. Therefore, heterologous vaccination was proposed precisely to avoid exposing people to this very small risk thrombosis with the second AstraZeneca dose. A risk – we repeat – in the order of one every 100 thousand, which concerns only the Anglo-Swedish formulation and which therefore could lead to choose the heterologous path for this.

When it comes to adverse effects, however, it also includes that whole range of side symptoms induced by vaccination, most of the time not serious and self-resolving. The cases here are very numerous, but let’s take into consideration as an example the adverse effect of temperature. According to a study conducted in Oxford and published in May by the Com-Cov Study Group starting from a sample of over 400 people, AstraZeneca + Pfizer gave fever after the second dose in 34% of cases, while AstraZeneca + AstraZeneca only the 10% of the time. (For the record, although this is not the choice to make, Pfizer + Pfizer gave a fever 21% of the time, while the reverse heterologous Pfizer + AstraZeneca 41%.) The most interesting aspect, such as they commented scientists, is that the proportions they remained the same even considering other mild adverse effects, such as headaches, body aches, fatigue and chills.

However, the fact that mixed vaccination gives more frequent mild adverse effects is not bad news, on the contrary: it is rather the confirmation of a greater reactogenicity of this heterologous combination compared to the dual administration of AstraZeneca. On the flip side, however, there is the fact that still there is no data with regard to any medium effects e long term mixed vaccination, as it has only recently begun to be studied.

The unknown of duration and the inevitable heterologous

There are many other aspects that can be considered. For example, the question of whether mixed vaccination increases or decreases the time of immune protection. In the abstract there should be no difference, because in any case the end result of vaccination is to train the immune system to recognize the medesima proteina spike of the Sars-Cov-2 virus. In practice, however, to date there are no data to know whether there is a gap of a few months in the duration of the protection, nor on which side the gap itself is.

Finally, but certainly not least, there is the question of what will happen in the long run from the more general point of view of pandemic and of vaccination campaign. If, as deemed likely, further vaccination is required in the months and years to come, it is unlikely that the AstraZeneca formulation will continue to be received, which in fact will be abandoned at least throughout the European Union. In perspective, therefore, those who received the first dose of Vaxzevria vaccine will find themselves anyway sooner or later with great probability in a heterologous condition, and the choice facing us now is essentially if pass immediately to mixed administration, or whether to continue for now on the homologous vaccine route e postpone mixed vaccination with an unspecified future.

Categories:   Science