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3 COVID-19 Exposures Provide Immunity Against Omicron

Triple COVID-19 vaccination or infection-plus-vaccination hybrid immunity induces high-quality antibodies, capable of neutralizing even the Omicron variant.

SARS-CoV-2, the virus that causes coronavirus, has continued to evolve and mutate throughout the pandemic. The most recent variant of concern, Omicron (B.1.1.529), has demonstrated an unprecedented ability to cause infections even in fully vaccinated individuals.

A team of researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich, Helmholtz Munich, and the Technical University of Munich has been looking for the best way to teach the immune system to battle Omicron.

They found that a total of 3 exposures to the viral spike protein allows the body to produce a high quality and high quantity of virus neutralizing antibodies that vigorously bind to the spike protein, even neutralizing Omicron. These high-quality antibodies were found in triple-vaccinated people, people who recovered from COVID-19 and then received 2 vaccine doses, and double-vaccinated people who had a breakthrough infection.

The investigators identified voluntary participants who had contracted COVID-19 during the spring 2020 wave, comparing them to a second group of people who had not been infected. The study cohort included 98 people who recovered from COVID-19 and 73 people without prior infection. Both groups were later offered the Pfizer-BioNTech mRNA vaccine and then monitored for nearly 2 years.

The investigators used live-virus neutralizations assays in their analysis of the participants’ blood. They looked for several factors to gauge immunity, including the antibody concentration to the viral spike protein, the binding strength of these antibodies, and their ability to neutralize infection with COVID-19 variants.

The investigators found that the immune system’s ability to neutralize the virus was only slightly linked to the antibody titer. Instead, the most critical measure was how effectively the antibodies bind to the virus and debilitate the infection.

Predictably, Omicron was the most resistant to the neutralizing antibodies. However, Ulrike Protzer, the study’s lead author and a professor at the Institute of Virology at the Technical University of Munich and Helmholtz Munich, noted, “A new finding of our study is that people require three separate exposures to the spike protein to build up high-level neutralizing activity against all viral variants, including Omicron.”

Triple-vaccinated people with no prior COVID-19 infection had nearly the same titer and quality of neutralizing antibodies against Omicron as people who had a breakthrough infection caused by the Delta or Omicron variant.

Protzer added, “The immunity built up or strengthened by means of vaccination is key to effective protection against future variants of the virus. A recent breakthrough infection–as irritating and undesirable as it is–has in fact the same effect as an additional vaccination on this important arm of the immune system.”