Primary vaccination with two mRNA vaccine doses was not sufficient to achieve adequate antibody levels for infection protection against the spike protein of the SARS-CoV-2 Omicron variants. Only the third and fourth COVID-19 vaccinations lead to high antibody levels and increased protection against COVID-19 infections caused by the Omicron virus.
Little was known in the spring of 2022 about the additional benefit of a third and fourth vaccination with the Comirnaty mRNA vaccine (BioNTech/Pfizer) for protection against COVID-19 infections caused by the Omicron variants of the SARS coronavirus 2 (CoV-2) – there were no vaccines adapted to Omicron variants at this time, however the Omicron variants BA.1 and BA.2 were already circulating. The spike protein encoded in the Comirnaty vaccine was that of the original SARS-CoV-2 variant.
Researchers from the Paul-Ehrlich-Institut and the Main-Kinzig Clinics investigated the antibody response achieved over time by Comirnaty vaccinations against various SARS-CoV-2 variants. They identified an increase in antibody titres after booster vaccination(s) and a decrease in titres over time against the SARS-CoV-2 variants after vaccination. In addition to the detection of binding and neutralising antibody 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.
Two vaccinations with the Comirnaty mRNA vaccine did not lead to an adequate formation of neutralising antibodies against the Omicron subvariants BA.1 and BA.2, which have been dominant since January 2022. In contrast, an initial booster vaccination increased the levels of IgG and IgA antibodies directed against the receptor-binding domain of the Omicron virus variants, as well as their virus-neutralising capacity.
Five to six months after the third vaccination, however, no Omicron-neutralising antibodies were detected in 36 percent of the sera examined. All sera were still able to efficiently neutralise the Delta variant, which dominated in 2021.
A second booster vaccination with Comirnaty (fourth vaccination in total) again caused a significant increase in antibodies that neutralised the Omicron, Delta, and Wuhan variants. This increase then fell off again as previously observed.
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.
Our study results indicate the importance of COVID-19 booster vaccinations for high levels of broadly neutralising antibodies against various SARS-CoV-2 variants.
Prof Dr Eberhard Hildt (Head of the Virology Division at the Paul-Ehrlich-Institut)
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 (Basel) 10: 796.