Monday, January 24

Year and a half of pandemic without understanding immunity against covid | Science


A Palestinian receives the Sputnik vaccine against the coronavirus in the Khan Younis refugee camp in the southern Gaza Strip.
A Palestinian receives the Sputnik vaccine against the coronavirus in the Khan Younis refugee camp in the southern Gaza Strip.MOHAMMED SABER / EFE

The advancement of the delta variant and its hypothetical ability to outwit the immune system has become the perfect alibi for RNA vaccine manufacturers, who have been pushing for days for a third booster dose to be approved.

It is a possibility that has been considered since almost the beginning of the pandemic and that would mean enormous extra income for companies like Pfizer, the main champion of the third injection. The problem is that their arguments are based on confusing, secret and premature data, as highlighted by the main US medical authorities, who have declined the third dose until there is more data. The World Health Organization has also questioned the need for this new dose and has criticized that it is debated nowWhen in much of the developing world there are millions of people who have not even received the first injection.

Carmen Cámara, immunologist at Hospital La Paz in Madrid and member of the Spanish Society of Immunology (SEI) affirms that “Pfizer was the first in the vaccine race and achieved an advantageous position that now it does not want to lose. It is a 100% commercial movement ”. “This does not mean that in the end you have to end up putting a third dose, but now there is no data and it is not the time to decide,” the expert decides. “Now what matters is to finish all the second doses in developed countries and extend vaccination to the rest of the world with the most appropriate vaccines for their circumstances, which will be from Janssen, Astra Zeneca, Novavax or others more suitable for their conservation needs. cold and its price. That is the priority and it is not what is going to give money to Pfizer ”, he adds.

The main scientific argument of Pfizer and BioNTech is that they have seen a drop in antibodies against the coronavirus between 6 and 12 months after full vaccination. A third dose would multiply between 5 and 10 times the blood levels of these proteins capable of neutralizing the virus.

The problem with basing immunity decisions on the amount of antibodies is that it is not yet known what levels are necessary to prevent infection and disease.

The data comes from a clinical trial organized by the company. They are partial results that have not yet been reviewed by independent experts or published in a scientific journal. The company also cites the real experience of Israel, a country very advanced in vaccination thanks to its agreements with this company and which has ensured that the efficacy of the vaccine drops at six months and allows reinfection with the delta variant. The country has made the controversial decision to start giving a third dose to especially vulnerable people, such as those with a transplanted organ. But data from the country also shows that protection against hospitalization and severe covid by the delta variant of the two doses of the vaccine is virtually the same as with other variants.

César Hernández, head of the Department of Medicines for Human Use of the Spanish Medicines Agency, admits: “We are all waiting to see how conclusive the data on possible vaccine failures are.” Health authorities must strike a difficult balance. “If we wait for a lot of real data on cases in which vaccines fail, there will be more people exposed to the contagion, and if we make the decision too soon based on an indirect variable such as the level of antibodies, we may end up giving another dose to people who it doesn’t need it ”, he details.

The problem with basing immunity decisions on the amount of antibodies or even the amount of lymphocytes, recalls Antonio Bertoletti, from Duke University (USA), is that it is not yet known what levels are necessary to avoid infection and disease . This immunologist published one of the studies showing that after an infection – and probably also after vaccination – a person generates dozens of different lymphocytes. Each one attacks a very specific part of the virus, which prevents it from escaping whatever variant it is.

Another argument in favor of the third dose comes from a study published a few days ago that exemplifies a problem that the world has been facing since the beginning of the pandemic. The work showed that antibodies from people who have only received one dose of the vaccine do not completely neutralize the delta variant, while two doses do. These data come from laboratory experiments – and not from real cases – in which the virus is grown in a container and blood from those vaccinated or cured of COVID is added to measure the neutralization capacity.

Since the beginning of the pandemic, the vast majority of studies on immunity have focused on these proteins of the immune system, which is an enormous limitation, since they leave out the activity of the cells of the immune system, especially the lymphocytes that make up a sort of an elite army. Months, even years after the antibodies have disappeared from the blood, memory lymphocytes can reactivate when the virus appears again and orchestrate a new defense, including the production of new antibodies. The most interesting thing is that up to now these immune cells have proven to be invulnerable to the mutations that the virus accumulates in its different variants. Several studies have shown that the antibodies of vaccinated people or those who have passed the COVID neutralize all known variants so far. For now there is no data on the delta, but logic indicates that it will also be able to handle it, say the experts consulted.

The president of the SEI, Marcos López-Hoyos, adds that in Spain, at the moment, there is no consolidated data on how many reinfected there are and with what variant, although they would be “exceptional” cases. At the Marqués de Valdecilla de Santader Hospital, where he is the chief of immunology, only 2% of the total infections had the complete vaccination schedule, he explains. “People who have been fully vaccinated are protected,” he says.

A year and a half after the start of the pandemic, it is still not known how long the natural immunity or that of the vaccine lasts

The immunologist Jordi Cano Ochando is studying the level of cellular immunity of the general vaccinated population and also of immunosuppressed people in Spain, where he works at the Carlos III Health Institute, and in the United States, where he is affiliated with the Monte Sinai Hospital in New York . “For now we are seeing a good immune response to the new variants,” he says.

Most of the experts consulted think that there is still no data to give a third dose to the general population and that it will probably never be necessary with a single exception: some immunosuppressed patients, such as those who have just received transplants. The job now would be to measure their levels of antibodies and lymphocytes, which is not always easy.

A year and a half after the start of the pandemic, it is still not known how long the natural immunity or that of the vaccine lasts. It is completely logical. The best way to find out is to let time pass. “For now we know that cellular immunity lasts a little over a year”, highlights Carmen Cámara. This protection may be much longer. Bartoletti highlights that “in the case of SARS [otro coronavirus que emergió en 2002 y mató a unas 800 personas] memory immune cells were still active 17 years later ”. “These memory lymphocytes are at very low levels in the blood, but some of them are quartered in the bone marrow or lymph nodes and are always ready to return to action when needed,” he says.

At this point, Spain faces a human resources challenge, says Cámara. “In general, in hospitals there are fewer immunologists studying cellular protection than microbiologists studying humoral protection. [anticuerpos] and this partly explains why we do not yet have enough data to establish protection correlates [saber qué niveles de linfocitos protegen de la infección y la enfermedad]”, Explain. “The commercial cell determination costs about 50 euros per patient, hence it cannot be extended to everyone, but in selected cases it is perfectly acceptable. The bottleneck is that it has to be an immunologist who selects the cases and makes the interpretation ”, he adds and ventures that the problem could be solved by creating a National Center for Immunology, just as there is already one for Microbiology. “Perhaps that way they would pay more attention to us,” adds Cámara.

Manel Juan, head of immunology at the Hospital Clínico de Barcelona, ​​has a fatalistic approach to the third dose. “It is not justified now and it will not be in the future if the relationship between cost and benefit is taken into account,” he says. “But it will inevitably be approved because of fear of this wave in which infections continue to grow, although they do not have a great impact on hospitalizations or deaths, and also because it will not hurt to receive it. What will happen is that many people will not take the third dose and then we will know the real effect. So when the drug companies try to sell a fourth dose they may not succeed. In the end, who is interested in studying cellular immunity? To those who do not have economic interests ”, he adds.

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