Does a serological test before and after the vaccine make sense to see the presence of antibodies against Covid-19?

Does a serological test before and after the vaccine make sense to see the presence of antibodies against Covid-19?

Premier Draghi said he will do heterolysis because he developed low levels of antibodies after the first dose. Does such a choice make sense? And how reliable are serological tests to verify the effectiveness of vaccination?

(photo: chinaphotographer via Getty Images) It seems to be done on purpose: when it comes to anti-Covid-19 vaccinations, chaos is rampant. Always. After the mess (communicative and not only) that accompanied vaccinations under 60 with the AstraZeneca vaccine, in recent days it was Prime Minister Mario Draghi who threw himself into the fray, with words that mix two of the hot topics of recent weeks: heterologous vaccinations and analysis of the antibody titer. "The heterologous works - explained the premier at the press conference - I booked myself to be a heterologous, the first AstraZeneca I did gave a low antibody response and so I recommend that I do the heterologous. So how it works for me works for those under 60 ”. Unfortunately there are even more doubts about the efficacy of the heterologous and the reliability of the antibodies to evaluate the effect of vaccination, and the indications of the experts are rather ambivalent (in addition to the fact that at the moment the option mentioned by Draghi is not is available in all regions for the rest of the Italians over 60). However, let's see what the available research says.

The Draghi affair

In the case of the Italian premier, the question is not so much linked to the safety of the second dose with a vaccine different from that of the first, as it was for many Italians under 60 to who was forced to change vaccine during the race in response to the possible dangers of thrombosis associated with the AstraZeneca preparation. On the contrary: for Mario Draghi the use of a mix of different drugs would be preferable to maximize the immunity offered by vaccination. After carrying out the first dose, the analyzes must have indicated a lower than expected presence of antibodies. And this must have prompted the prime minister's doctor to recommend a booster with a different vaccine. In this sense, the strategy has a rather solid, albeit still limited, scientific basis. First of all, viral vector vaccines, such as those of AstraZeneca and Johnson & Johnson, have a tendency to be less effective if repeated several times: our immune system does not react only to the Sars-Cov-2 antigen carried by the vaccine, but also to the adenovirus acting as a vector, and when a booster is performed there is a good chance that the immune response will eliminate a considerable part of these adenoviruses before they reach the cells and do their job, limiting the effectiveness of the injection.

For some decades, moreover, it has been increasingly evident to the scientific community that carrying out first and second doses with different vaccines (which obviously carry the same antigen) tends to give better results than a homologous vaccination. Why is not yet fully understood, and probably the effect also depends on the technologies used, and the order in which the vaccines are administered. According to experts' hypothesis, different vaccine technologies activate different components of our immune system, and under the right conditions this can actually enhance the overall effect of vaccination

At the same time, different vaccines use slightly different versions of the vaccine. viral antigen and therefore mixing more vaccines can produce a more complete response, with more antibodies being activated against the pathogen, and therefore also greater resilience towards the appearance of new variants of the virus. As we said, the order of the addends is also important in heterologous vaccinations. In the case of Covid vaccines there is a lack of reliable data on which is the best combination (obviously, since the vaccines have been on the market for just 6 months), but some clues suggest that it is precisely the first dose with an adenovirus vaccine (such as AstraZeneca) and mRna boost (Pfizer or Moderna) to ensure maximum efficacy.

The dosage of antibodies

Moving on to the use of serological tests to verify the efficacy of vaccination, a today there are no official indications, and the decision is left to doctors and citizens, on which obviously also the possible costs (it must be said, content) of the examination fall. However, the expert opinion seems rather compact: a useless test, which offers no guarantees on the effectiveness of vaccination. It is the same opinion expressed, in America, by the FDA, which advises the population against the use of the dosage of antibodies, on the basis of a lack of reliable data with which to interpret a possible positive or negative result.

It is known that a small percentage of vaccinated people, regardless of the vaccine they receive, will not develop the desired immunity to the disease. But it is not certain that a lower than expected level of antibodies identifies patients at risk: immunity to Sars-Cov-2 does not seem to be linked solely to the presence of high levels of antibodies, and not all serological tests available on the market are equally effective in identifying the antibodies produced in response to the vaccine.

Even at the level of basic research, there are still few certainties regarding the indicators that can help predict the level of immunization against Covid-19 delivered by a vaccine (or a previous infection) to a single patient. The levels of antibodies present in the blood are clearly one of the main candidates for this role, but they do not always prove effective, because immunity against a pathogen can take different paths.

The so-called adaptive immunity, that that we develop following contact with a virus or pathogen, is composed of two main elements: humoral immunity, linked to the activity of antibodies, and cellular immunity, in which T lymphocytes play the lion's share. In the first case, the viruses circulating in the body are identified by antibodies and then neutralized. In the second, that of cellular immunity, the process takes place inside the infected cells, through the expression of the viral antigen on their membrane and the activation of T lymphocytes, white blood cells that bind to the antigen and destroy the cell , to break the cycle of replication of the virus, but which can also perform other functions, for example by activating B lymphocytes to stimulate the production of antibodies following the encounter with the pathogen.

Humoral o cellular?

Both of these mechanisms go into action to fight infections, but which will be more important depends on many factors, not least the behavior of the virus itself. In the case of Sars-Cov-2 it is not yet clear which is more important to ensure immunity: some research seems to indicate that the level of neutralizing antibodies is an excellent proxy for the level of protection developed by a patient; others point in the direction of an important role for T lymphocytes, both in eliminating infected cells and as mediators that stimulate the production of new antibodies after detecting the virus. To further complicate the situation, then, there is the fact that preventing infection is not the only goal of vaccination: if a person can contract the virus but will never develop severe forms of the disease (because the immune system is ready to take action quickly to keep the situation under control), in terms of individual risks one can probably declare oneself satisfied. And this could be exactly what happens in vaccinated people who have low levels of circulating antibodies, if there are reservoirs of B lymphocytes ready to take action at the next encounter with the virus.

The situation, in short, it is complex, and it is too early to be certain about the immunological mechanisms that protect against Covid-19. Does it make sense to do a serological test after the vaccine to make sure it was successful? Difficult to say. Except that the best thing is to rely on the indications of your doctor, what can be said is that currently knowing the results of the test would not change the indications for patients in a particular way, given that all vaccinated persons are still advised to continue to follow the prevention measures that we have learned about in the last year of the pandemic, and that in almost all Italian regions at the moment it is not possible to choose a heterologous vaccination to improve the effects of the vaccine.

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