Antibody Response to Omicron…

and Other Virus Variants Effectively Replenished after 3rd and 4th COVID-19 Vaccination

12 / 2022

  • Two vaccinations with Comirnaty do not lead to adequate antibody levels against the SARS-CoV-2 virus variant Omicron.
  • A first booster vaccination (3rd vaccination) does increase the level of Omicron-neutralising antibodies, but this level decreases significantly after five to six months.
  • A second booster vaccination (4th vaccination) significantly increases antibody levels against Omicron.

Quote Professor Hildt

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Researchers from the Paul-Ehrlich-Institut (PEI) and the Main-Kinzig Clinics investigated the antibody response against various SARS-CoV-2 virus variants over time following COVID-19 mRNA (Comirnaty) vaccinations. After double vaccination against COVID-19, antibody levels against the Omicron variant are low. Omicron is currently the dominant variant in Germany. mRNA booster vaccinations significantly increase antibody levels against Omicron. Vaccines reports on the results.

The decreasing immune response against SARS-CoV-2 over time after COVID-19 vaccination and the emergence of SARS-CoV-2 variants leads to reduced infection protection and uncertainties in the prediction of protection against severe disease progression, particularly after infection with the Omicron variant of SARS-CoV-2.

Vaccine Syringe, Omicron lettering in the background (Source: viewimage/

Professor Eberhard Hildt, Head of the Virology Division at the Paul-Ehrlich-Institut, lead a research team comprised of colleagues from the Virology Division and the Safety of Medicinal Products and Medical Devices Division at the Paul-Ehrlich-Institut and from the Main-Kinzig Clinics. The team investigated antibody response following COVID-19 vaccinations. They identified an increase in antibody titres after booster vaccination(s) and a decrease in titres against the SARS-CoV-2 variants over time after vaccination. In addition to the detection of binding and neutralising titres, the change in the affinity, i.e. the stability, of antibody binding to the spike protein of various virus variants over time was also studied.

Booster Vaccinations Increase Protection against Omicron Variant

Two vaccinations with the mRNA vaccine Comirnaty did not lead to the adequate formation of neutralising antibodies against the currently dominant Omicron variant. In contrast, a first booster vaccination increased the levels of IgG and IgA antibodies directed against the receptor binding domain of the Omicron virus variant, as well as their virus-neutralising capacity. Although Omicron spike protein-binding antibodies were still detectable five to six months after the third vaccination, no Omicron-neutralising antibodies were detected in 36 percent of the sera examined. On the other hand, all sera were able to efficiently neutralise the Delta variant, which was widespread in Germany last year.

A second booster vaccination with the mRNA vaccine Comirnaty – which corresponds to a fourth COVID-19 vaccination – once again led to a significant increase in neutralising antibodies against the Omicron, Delta and Wuhan variants.

No Difference between Homologous and Heterologous Vaccination Schedule

When comparing the different vaccination strategies for the primary vaccination course (homologous vaccination with Comirnaty only or the combination of Vaxzevria (AstraZeneca) and Comirnaty), there was no difference in the breadth of the immune response after booster vaccination.

Original Publication

Hein S, Mhedhbi I, Zahn T, Sabino C, Benz NI, Husria Y, Renelt PM, Braun F, Oberle D, Maier TJ, Hildt C, Hildt E (2022): Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS‐CoV‐2 after Third and Fourth Vaccination.
Vaccines 10: 796.