Dr. Simone Hoffmann (Ulm/ DE), Alina Seidel (Ulm/ DE), Prof. Dr. Bernd Jahrsdörfer (Ulm/ DE), Dr. Sixten Körper (Ulm/ DE), Carolin Ludwig (Ulm/ DE), Christine Vieweg (Ulm/ DE), Dan Albers (Ulm/ DE), Pascal von Maltitz (Ulm/ DE), Dr. Rebecca Müller (Mannheim/ DE), Prof. Dr. Ramin Lotfi (Ulm/ DE), Prof. Dr. Patrick Wuchter (Mannheim/ DE), Prof. Dr. Harald Klüter (Mannheim/ DE), Frank Kirchhoff (Ulm/ DE), Prof. Dr. Michael Schmidt (Frankfurt a. M./ DE), Prof. Jan Münch (Ulm/ DE), Prof. Dr. Hubert Schrezenmeier (Ulm/ DE)
Background
COVID-19 convalescent plasma remains a potential therapy of COVID-19, e.g. for new variants resistant to monoclonal antibodies and for patients with impaired immune response. Significant immune evasion by Omicron has raised concerns that antibody-based therapies may no longer be effective. We assessed whether superimmunized individuals, i.e. vaccinated convalescents, have sufficient cross-neutralization capacity against Omicron to be considered as plasma donors for passive immunotherapy.
Methods
We report the in-vitro neutralization capacity against SARS-CoV-2 variant B.1 and the Omicron subvariants BA.1, BA.2 and BA.5 of sera from convalescent individuals with and without boost by vaccination.
The study included 313 serum samples from 155 individuals with a history of SARS-CoV-2 infection, divided into subgroups without (n=25) and with SARS-CoV-2 vaccination (n=130). We measured anti-SARS-CoV-2 antibody concentrations by serological assays (anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S) and neutralizing titers against B.1, BA.1, BA.2 and BA.5 in a pseudovirus neutralization assay.
Results
Sera of unvaccinated convalescents did not effectively neutralize Omicron sublineages BA.1, BA.2 and BA.5. Neutralizing titers against B.1, BA.1, BA.2 and BA.5 were significantly higher in vaccinated compared to unvaccinated convalescents (p<0.0001) with 52.7-, 210.7-, 141.3- and 105.4-fold higher geometric mean of 50% neutralizing titers in vaccinated compared to unvaccinated convalescents. The increase in neutralizing titers was already achieved by one vaccination dose. Neutralizing titers were highest in the first 3 months after the last immunization event. Concentrations of anti-S antibodies in the anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S assays predicted neutralization capacity against B.1 and subvariants.
Conclusion
These findings confirm substantial immune evasion of the Omicron sublineages, which can be overcome by vaccination of convalescents. This informs strategies for choosing of plasma donors in COVID-19 convalescent plasma programs that shall select specifically vaccinated convalescents with very high titers of anti-S antibodies.
Offenlegung Interessenkonflikt:
None
Invited talks abstract/summary