how long is the protection of single-dose vaccines

In a context of global coronavirus vaccine shortageWith an increasing number of infections and no foreseeable horizon for the arrival of all doses, the government decided a week ago to change its vaccination strategy. The Federal Health Council has recommended postponing the second dose for all Covid vaccines for at least 12 weeks with the intention of prioritizing the application of the first component in the operational implementation. Immunize more people with the first and adjust the second.

One of the questions that still does not have a satisfactory answer is how long antibody production will persist and, therefore, the ability to defend against infection with this novel coronavirus. Another problem is the permanence of efficacy if the second dose is not administered within the recommended time frame.

Based on studies in infected patients, it is believed that immune memory conferred by these vaccines will last at least one year. The question then arises as to whether the fact of delaying the application of the second dose for three or four months could affect the effectiveness of the vaccines and / or the durability of the memory that they induce.

Of the three vaccines applied in Argentina (Sputnik V, Sinopharm and AstraZeneca / Covishield), the only one with scientific evidence to delay the second dose for at least 12 weeks, AstraZeneca (renamed Vaxzevria). However, Guillermo Docena, biochemist, immunologist and principal investigator at Conicet, suggests that with one dose of the Sputnik vaccine, immunity should be long-lasting as with that of AstraZeneca.

“By having the two adenoviral vector vaccines, the same that was observed in one should happen with the other“said the scientist, who is participating in a study on the immune response of the Sputnik V vaccine in vaccinated people in the province including the Leloir Institute, the Institute for Biomedical Research on Retroviruses and AIDS (INBIRS) and the Institute of Immunology and Physiopathological Studies (IIFP) of La Plata.

In the same vein, Jorge Geffner, senior researcher at Conicet, adds: “Studies carried out in the United Kingdom have shown that the efficacy of the Oxford / AstraZeneca vaccine would not be compromised, nor the extension over time of immune memory which induces. It is logical to assume that what is observed in the UK can be extrapolated to other vaccines also based on adenoviral vectors, such as Sputnik V. In fact, research conducted in our country has shown that the application of ‘A single dose of Sputnik -V generates significant levels of antibodies in 90% of vaccinated individuals’.

Geffner specifies that “it remains to analyze in a particular way the response induced by Sinopharm, prepared from whole inactivated viruses, in order to establish the convenience or not of delaying the application of the second dose, in order to reach a larger segment of the population in a shorter period of time, in the first place to instead, those over 60 ”.

Efficacy and antibodies

How effective are these vaccines? Martín Stryjewski, head of hospitalization at CEMIC and master of health sciences at Duke University, details that AstraZeneca is up to 76% effective (ability to prevent infection) at three months with a single dose, “but this does not reduce asymptomatic cases with this pattern: it only has an effect on clinical disease, preventing three out of four infections ”.

Sputnik V is 73% effective until day 21 and Moderna (which is not used here) is 62% at 28 days, both before the second dose, says Stryjewski. Carlos Regazzoni, physician and former head of PAMI, adds: “Overall, these vaccines are effective at two doses, ranging from 70% to 90%, in preventing serious illness and death, but is reduced by 30% with a single dose and probably lasts less (how much is unknown) too. “

Does the first dose still generate antibodies? Or could it not happen? “It’s not normal, but occurs in 10-20% of people vaccinated for Covid. We saw it with Sputnik and it is published in the books that evaluate AstraZeneca. With Sinopharm, it’s similar, even if nothing has been published from phase 3 ”, explains Docena.

The amount of antibody that can be acquired with the first dose is very variable and depends on the genetics of each organism. “All do not produce the same amount with the vaccine, some do not even generate them with the first dose and only acquire them with the second, that is to say when 100% of the vaccinated produce antibodies and in quantity . There, individual heterogeneity is diluted “, expand. And he specifies that the other cellular mechanisms induced with the vaccine must also be taken into account.

Along the same lines, Regazzoni emphasizes: “The amount of potency of the antibodies generated by the vaccine depends on design factors and who receives it. For this reason, in some people the vaccination will have been effective in preventing infection, in others it may only prevent severe forms and in a different group it does not work and the body is likely to be infected with the virus because if it had not been vaccinated “.

Since no one knows how long vaccine immunity lasts, it’s important to see what happens to natural immunity. Stryjewski points out that the majority, 90% acquire antibodies (humoral immunity) with the ability to neutralize the virus, but about a quarter no longer have them within six months. “Losing antibodies doesn’t necessarily mean losing immunity, because on re-exposure they could produce them again quickly and / or be defended by trained T cells (cellular immunity) which are not measured in practice. For this reason, the markers used today to quickly understand whether or not there is immunity are antibodies, ”he explains.

With a single dose, this is the percentage loss of these antibodies in a significant percentage of patients within six months, with which the protection of the vaccine could be lost or diminished more quickly than if the two-dose regimen were given. “In other words, one dose would reduce clinical disease in the short to medium term, although it would not be the best long-term strategy to stop the transmission of the virus», Warns the CEMIC hospital manager.

Cellular memory

The specialists consulted understand that each vaccine induces cellular (generated by T lymphocytes, responsible for cell-mediated immune mechanisms) and humoral (B lymphocytes, responsible for the generation of antibody-mediated immune mechanisms) memory. This memory is responsible for maintaining the immune response over time.

In this sense, Daniela Hozbor, vaccine expert and researcher at Conicet, notes that “the first dose is not safe. Reduces viral load and produces a cellular response. The antibody level doesn’t mean anything in terms of how protected I am. It is necessary to observe the correlate of protection which would imply the neutralizing antibodies and also a cellular response ”.

Infectologist Pablo Bonvehi refers to the fact that studies of different vaccines show that antibodies start to rise 10 to 14 days after the first dose, but that due to their own dynamics, it is not expected that ‘they decrease sharply, but rather slowly over time. Over the weeks: “Even if the antibodies decrease, the person already has immunological memory, which generates a very rapid response after encountering the virus and this will surely provide protection.”

For her part, Docena points out that “with other vaccines, the memory can last for years and in fact it is inoculated only once in a lifetime for many of them, but when we talk about Covid it is not clear how long the acquired immunity lasts for sure“.

However, Geefner states that “in 80% of infected patients, a B-cell-mediated memory response is observed, which results in the production of antibodies and lasts for at least nine months. The memory response mediated by T cells appears to persist for longer periods. “

AS