A diagnostic strategy for adjusting Covid-19 vaccination to individual immune state

Purpose: We describe a diagnostic procedure suitable for scheduling (re-)vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) according to individual state of humoral immunization. Methods: To clarify the relation between antibody measurements and immune protection, we monitored 124 individuals before, during and six months after vaccination with Spikevax (Moderna). Antibodies against SARS-CoV-2 spike (S1) protein receptor binding domain (S1-AB) and against nucleocapsid antigen were measured by chemiluminescent immunoassay (Roche). Virus-neutralizing activities were determined by surrogate assays (NeutraLISA, Euroimmune; cPass, GenScript). Neutralization of SARS-CoV-2 in cell culture (full virus NT) served as ex-vivo correlate for humoral immunity. Results: Vaccination responses varied considerably. Six months after 2nd vaccination, participants still positive for full virus NT were safely discriminated by S1-AB levels ≥1000 U/ml. The full virus NT-positive fraction of participants with S1-AB levels <1000 U/ml was discriminated by virus-neutralizing activities >70 % as determined by surrogate assays (NeutraLISA or cPas). Participants that were full virus NT-negative and therefore presumably insufficiently immune protected could be identified by the above procedure with a sensitivity of >83 % and a specificity of >95 %. Conclusion: In summary, the described diagnostic tool strategy enables individualized (re-)vaccination schedules based on simple and rapid measurement of serum-based SARS-CoV-2 antibody levels. Our data apply only to WUHAN-type SARS-CoV-2 virus and the current version of mRNA vaccine from Moderna. Adaptation to other vaccines and more recent SARS-CoV-2 strains will require modification of cut-offs and re-evaluation of sensitivity/specificity.Study numbers: 2021-1455 and 2020-1259_1, Ethics Committee Med. Fac. HHU.