It takes 3 exposures to COVID to generate broad immunity

A study by the Technical University of Munich indicates that it is necessary to have been exposed three times to the spike protein of the coronavirus in order to generate high-quality antibodies that provide a broad immune response.

It takes 3 exposures to COVID to generate broad immunity

The immune system develops a high-quality antibody response after three encounters with the coronavirus spike protein. The antibodies generated in this triple exposure are also able to efficiently neutralize the omicron variant. This applies to people who received the triple vaccine, those who recovered and then received two doses of vaccines, and people with two doses of vaccine who subsequently experienced an infection. These are the results of a study that tracked the antibodies of vaccinated and recovered individuals for two years.

Since the start of the COVID-19 pandemic, SARS-CoV-2 has continued to evolve, with new variants of concern spreading rapidly. Highly contagious and partially capable of evading the immune response, omicron has become the dominant variant in most countries, and has pushed governments to speed up the administration of third doses in order to strengthen the immunity of their population. .

A team led by Professor Ulrike Protzer, Director of the Institute of Virology at the Technical University of Munich (TUM) and Helmholtz Munich, Percy Knolle, Professor of Molecular Immunology at TUM, and Prof. Oliver T. Keppler (Max von Pettenkofer Institute and Gene Center Munich at LMU). As they report in Nature Medicine, a total of three viral spike protein exposures leads to the production of virus-neutralizing antibodies not only in high quantity, but also in high quality. These high-quality antibodies bind to the viral spike protein more strongly and are also capable of effectively combating the omicron variant. This applies to people vaccinated three times, people who have recovered from COVID-19 and then received two vaccines, and people vaccinated twice who later had an advanced infection.

The study followed the patients for two years

Since the beginning of the pandemic, volunteer participants from the staff of TUM’s Klinikum rechts der Isar university hospital at risk of infection participated in the study and underwent regular tests. The researchers identified people who had contracted SARS-CoV-2 during the first wave of the pandemic in the spring of 2020 and compared them to a second group of people who had not been infected. Subsequently, both groups were offered vaccination with the BioNTech/Pfizer mRNA-based COVID-19 vaccine and were followed for nearly two years. The cohort consisted of 98 recovered people and 73 people without previous infection.

“This longitudinal study is particularly exciting, because we can follow how the immune response against the virus evolves and after vaccination,” says Professor Knolle, pointing to a study by the team, which has just appeared in Nature Communications. In the new study, the team now defined several parameters in the study participants’ blood: the concentration of antibodies against the viral spike protein, the binding strength of these antibodies, and their ability to neutralize the infection of SARS-variants. CoV-2 in cell culture. To estimate the extent of protective immunity, the last two parameters are particularly important. The study revealed that the immune system’s ability to neutralize the virus correlates only weakly with antibody titer. Rather, the efficiency with which these antibodies bind to the virus and thus inactivate the infection was critical.

As predicted from its many mutations, omicron exhibited the most pronounced evasion of neutralizing antibodies compared to all other viral variants tested. “For omicron, much more and better antibodies are needed to prevent infections,” says Prof. Keppler. The researchers developed a new virus neutralization test, which allowed them to test many serum samples for antibodies and different virus variants at high throughput rates. Prof. Protzer adds: “A new finding from our study is that people require three separate exposures to the spike protein to develop high-level neutralizing activity against all viral variants, including omicron.”

As the scientists report, several constellations are possible for these three peak encounters. Triple-vaccinated individuals without prior SARS-CoV-2 infection had nearly the same titer and quality of neutralizing antibodies against omicron as convalescent vaccinated individuals or individuals who had advanced delta or omicron infection. According to Professor Keppler: “In all cases, the neutralizing activity reached equally high levels and this was paralleled by a higher binding strength of the antibodies.” Professors Protzer and Knolle agree: “Immunity built up or strengthened through vaccination is key to effective protection against future variants of the virus. A recent breakthrough in infection actually has the same effect as an additional vaccine on this important arm of the immune system.”



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