Quebec’s public health has obviously won its bet. A 16 week interval between the two doses of the COVID-19 vaccine generates an excellent immune response that is similar to the optimal response expected. This is what reveals a new study carried out in Montreal and on-line these days on a preprints site.
Remember that at the very beginning of the vaccination campaign, faced with the scarcity of vaccine doses, the health authorities of Quebec decided to delay the administration of the second dose in order to be able to offer vaccine protection to a greater number of people. vulnerable. This strategy deviated from the manufacturer’s protocol, according to which the second dose was to be administered three to four weeks after the first. “In principle, we should have kept doses in reserve in the freezer to administer them three weeks after the first dose, but we decided to extend the time between the two doses because there were analyzes carried out in particular by the Dr Gaston De Serres, from the INSPQ, who showed that the efficacy of the vaccine against severe forms was still present 16 weeks after the first dose. These data therefore justified the strategy adopted, which consisted in administering a first dose to as many people as possible and giving the second dose later than foreseen in the manufacturer’s protocol. Then, as the arrival of vaccines improved, the interval between doses was shortened, ”recalls immunopathology researcher Andrés Finzi, from the CHUM Research Center.
The decision to delay the administration of the second dose was then strongly criticized. Many feared that this strategy would reduce the effectiveness of the vaccine. Some claimed that the second dose, which serves as a booster to boost the immune response from the first dose, would not produce the desired effect if administered later than recommended by the manufacturer.
Catching up with the gold standard
Andrés Finzi’s team set out to measure the immune response induced by the two doses of vaccine administered 16 weeks apart, as was the case in Quebec at the start of the vaccination campaign. These researchers therefore analyzed the blood of people who had never contracted SARS-CoV-2 and that of people who had been infected previously, at three different times: three weeks after the first dose, 12 weeks after the first dose in order to follow the immune response over time following a single dose and ultimately three to four weeks after the second dose which was given 16 weeks after the first.
During the 16 weeks after their first dose of vaccine, people who had been previously infected experienced a barely noticeable decrease in IgG antibodies to a spike of the S protein of the virus where the receptor binding domain is located. (RDB), as well as antibodies directed against the whole spike. The content of these antibodies remained very high, whether these people had received one dose or two doses of the vaccine, “which is in line with the recommendation of the Quebec Immunization Committee that only one dose. vaccine may be sufficient for people who have already contracted the virus, ”says Finzi.
Last June, Andrés Finzi and colleagues from California had already shown in the magazine Science that, in people who had been infected with SARS-CoV-2, the immune response induced by a single dose of vaccine was extraordinary. “In terms of the immune response, these people represent the absolute benchmark that we want to reach”, underlines the researcher while insisting that this observation “is above all not an invitation to be infected in the hope of obtaining an optimal immune response! “.
As for people who had never been infected, their antibodies increased rapidly after their first dose of vaccine, then gradually decreased over the next 12 weeks, until the second dose of vaccine, which was then induced a significant rise in antibodies, which reached the absolute reference levels, ie those of people who were infected before their first dose of vaccine.
In terms of the immune response, [les personnes qui avaient été infectées par le SRAS-CoV-2 et vaccinée une fois] represent the absolute benchmark that we want to achieve.
Advantages?
The effectiveness of the vaccine during the 16-week interval between the two doses of vaccine was probably explained by the very good effector response of the antibodies, called antibody-dependent cell cytotoxicity (ADCC) following the first dose, believes Mr. Finzi. This ADCC response allows the antibodies generated by the vaccine to call for help patrolling immune cells in the body, such as NK cells (natural killer) and macrophages, which know how to recognize the signals launched by antibodies attached to infected cells and which come to help them by killing them.
Now, we are investigating whether extending the time between doses may provide certain benefits, particularly in terms of the longevity of immune memory.
All in all, “three weeks after the second dose of vaccine given 16 weeks after the first, the immune response is very good,” says Finzi. The levels of neutralizing antibodies have joined those of previously infected and vaccinated people (the gold standard), and they are able to neutralize the Alpha, Beta and Delta variants, even this other coronavirus what SARS-CoV-1 is. These antibodies also have a very good DCC function. “People who have received their second vaccine after a very long delay can therefore be reassured,” he says.
“Our results show that people who were immunized with doses given within 16 weeks have a very good immune response, but that doesn’t necessarily mean the other approaches weren’t good,” he says. . Now, we are investigating whether the lengthening of the time between doses can give certain advantages, in particular at the level of the longevity of the immune memory and the need or not of a third dose and, to find out, we must do more studies. “
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