The debate on boosters based on current immunological knowledge. The third dose was foreseen, but it cannot be anticipated too much, while with close and unexplained fourth doses there is a risk of paralysis of the immune system. Here are the reasons
One year after the first vaccine doses, the coronavirus is imposing new challenges and difficult choices on the world, even from a scientific point of view. Faced with the extraordinarily contagious variant of Omicron, Israel has begun to offer
fourth doses (Pfizer vaccine) to some high-risk groups and many countries (including Italy) are proceeding with the third dose four months later.
Beyond the feasibility of administering third (or fourth) doses to the majority of the population every few months when so many in the world have not had access to the first doses, scientists are wondering whether this is the right strategy
also from an immunological point of view.
justifiable to think periodic vaccine boosters (we are talking about those with RNA that have been chosen for the third doses) so close together? How long will they be needed? With what effect? Wouldn’t it be better to wait for a specific booster for variante Omicron? And what if SARS-CoV-2 still mutates? These are questions without certain answers, but on which predictions can be made based also on what we know about immunology and the vaccines used so far.
First, the need for third doses.
It is normal that they are given – explains Sergio Abrignani, immunologist at the State University of Milan -, with the exception of vaccines based on live attenuated viruses that require a single dose, the other vaccines that are given to “virgin” individuals (which have never seen the microorganism you want to vaccinate against) they need three doses. The first two serve to trigger a strong immune response (which we call “effector”), which works well in the short term, but which tends to lose its effectiveness in a few months. With so many vaccines that we have been using for decades (including Hepatitis B, Tetanus, Hemophilus, Meningococcus B) the third dose (spaced at least 6 months from the first two doses) triggers a long-term memory, which allows us to make subsequent boosters (“Fourth doses”) after 5-10 years. In an explosive phase of the pandemic due to the Omicron variant, governments have decided to bring the third dose forward from 6 months to 3-5 months to prevent the expected decline in the immune response. It is necessary to know that the more the third dose is anticipated (for example to the third month) the more a prompt “effector” response should be favored, but the triggering of a long-term immunological memory is probably disturbed. There is therefore an immediate advantage in quickly inducing a new “effector” response, which could have as a downside a reduced “long-term” memory.
The reminders, in fact, are useful at this time, increase the levels of antibodies and help (in part) to prevent infections as well. Consequently, they can relieve pressure on the health system by temporarily slowing the spread of the virus.
it is conceivable to anticipate the third dose e
continue with the fourth doses every few months?
We have never vaccinated the entire population while a pandemic of this size was raging, in this case we have already made a choice by anticipating the third dose to 4-5 months, but I think it is not a good idea to shorten too much and vaccinate every three months – he says. Abrignani -. Obviously no one has experience with mRNA vaccines, so we rely on what I know from other vaccines and immunology, but based on what we know, if you vaccinate every two to three months to continuously stimulate the “effector” response, after a while, the opposite effect may occur. The immune system could “anergise” (anergy the inability of an organism to react to infections or to contact with an inoculated substance with antigenic power, ed.). There is a risk of the paradoxical effect of “paralyzing” the immune response.
Israel has decided to proceed with the fourth dose
for healthcare professionals and the over 60s 4 months after the third Pfizer dose.
A fourth dose makes sense in two cases from an immunological point of view: because of a decline in immunological memory (which I would be surprised to happen a few months after the third dose) or because the variant that circulates largely escapes the “old” vaccine and therefore the fourth dose should be based on the new variant Spike. All vaccines in use (except for the flu) don’t need updates every year, Abrignani says.
It would make sense wait for an updated Omicron vaccine?
It would have made sense – argues Abrignani -, but an anti Omicron vaccine will be ready in April. The Omicron peak is expected to be reached in February. Of course, if we had an Omicron vaccine available now, it would have been better than the Wuhan vaccine. This wave must be overcome with the vaccines we have, which we know are not ideal for avoiding infections with this new variant, but which protect us very well from severe disease.
The open debate is not easy to solve: Omicron seems to be less lethal and current vaccines protect against serious diseases, so they could be enough, for the greater infectivity of Omicron (perhaps the most contagious virus ever to appear on the planet) poses significant problems, if not more to the health system, because the small percentage of people who need hospitals becomes a large number when the incidence of the pathogen is so high.
What to do then
a?
Before thinking about the fourth dose – declares Abrignani -: in the meantime we finish the third doses as soon as possible, which is essential because the normal completion of the vaccination cycle, and then we will also have to vaccinate those over 50 who have to take the first dose and who are at risk of severe disease in case of infection. Later, the Israeli data will come with the fourth dose and it will be possible to decide on the basis of solid data obtained on hundreds of thousands of people.
What to bet on
future of the recalls and on the holding of the third dose?
From the data obtained after the first two doses it is likely that with the third dose we will be very effectively protected (more than 80%) from severe disease for a long time. ” an anergy “of the immune system.
January 7, 2022 (change January 7, 2022 | 16:10)
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