gms | German Medical Science

29th Annual Meeting of the German Drug Utilisation Research Group (GAA)

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie

24.11. - 25.11.2022, Münster

A prospective study on the immunogenicity of different vaccines-schemes against SARS-CoV-2 in hospital staff – Insights from the Helios Hildesheim COVID-19 Vaccination Study (HelCO-Vac)

Eine prospektive Studie über die Immunogenität verschiedener Impfstoffschemata gegen SARS-CoV-2 bei Krankenhauspersonal – Einblicke in die Helios Hildesheim COVID-19-Vaccination Study (HelCO-Vac)

Meeting Abstract

  • corresponding author presenting/speaker Simon Dedroogh - Georg-August-University, Göttingen, Germany
  • Katharina Graf - Center for Clinical Trials, Witten, Germany
  • Sven Schmiedl - Center for Clinical Trials, Witten, Germany
  • Petra Thürmann - Philipp Klee-Institute for Clinical Pharmacology, Wuppertal, Germany
  • Sebastian Appelbaum - Research Methodology and Statistics in Psychology, Witten, Germany
  • Thomas Ostermann - Research Methodology and Statistics in Psychology, Witten, Germany
  • Reinhard Koß - Helios Klinikum Hildesheim, Hildesheim, Germany
  • Christian Theis - Helios Klinikum Hildesheim, Hildesheim, Germany
  • Zewarudin Zia - Helios Klinikum Hildesheim, Hildesheim, Germany
  • Jürgen Tebbenjohanns - Helios Klinikum Hildesheim, Hildesheim, Germany
  • Serge Thal - Department of Anesthesia I, Witten, Germany
  • Michael Dedroogh - Helios Klinikum Hildesheim, Hildesheim, Germany

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie e.V. (GAA). 29. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie. Münster, 24.-25.11.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. Doc22gaa10

doi: 10.3205/22gaa10, urn:nbn:de:0183-22gaa107

Published: November 21, 2022

© 2022 Dedroogh et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Background and objectives: The COVID-19 pandemic declared by the World Health Organization (WHO) in March 2020 continues, not least due to the now dominant, highly infectious omicron variants. A ray of hope in the fight against the pandemic are the m-RNA and vector-based COVID-19 vaccines, which have also been successively approved in the EU since the end of 2020, and which are highly effective in protecting against severe forms of SARS-CoV-2 infection. How do SARS-CoV-2 specific antibodies develop after basic immunization and after boost vaccination? Are there differences between the various vaccination regimens in terms of antibody development?

Methods: In the period from January to June 2021, a total of 1338 employees at the Helios Klinikum Hildesheim were vaccinated in a total of four cohorts in accordance with the applicable prioritization groups. Of these, 1206 subjects were included in the study, which corresponds to a study inclusion rate of 90%. Over time, the selection of vaccines followed the applicable recommendations of the national vaccination commission (Ständige Impfkommision, STIKO). This resulted in four different vaccine groups after the second vaccination with a corresponding number of subjects: mRNA vaccine BNT162b2 (BioNTech/Pfizer) with a vaccination interval of 3 weeks (homologous BNT-3, n=248) and 6 weeks (homologous BNT-6, n=262) as well as two groups with vector-based ChAdOx1 prime vaccination (AstraZeneca) and second ChAdOx1 vaccination after 12 weeks (homologous AZ-12, n=265) or as a heterologous vaccination regimen with a BNT162b2 vaccination after 12 weeks (heterologous AZ-BNT-12, n=343). As a study intervention, blood samples were taken serially from each study subject at prospectively defined study visits four weeks, three and six months after basic immunization and immediately before and four weeks and three months after boost vaccination to determine SARS-CoV-2 antibodies. On the one hand, anti-nucleocapsid antibodies were measured qualitatively, which indicate a natural infection with the virus. Furthermore, the anti-spike antibody (anti-S) was measured quantitatively up to an upper limit of quantification (ULoQ), and thus the vaccine-mediated immunogenicity was analyzed. The statistical analysis of categorical data is performed using frequencies, percentages and corresponding tests (Chi²- or Fisher's exact test and Mann-Whitney-Test). In addition, a Spearman Correlation was performed.

Results: After the basic vaccination, decreasing anti-S levels can be observed in all vaccination cohorts in the intra-group comparison over time until immediately before the boost vaccination (Figure 1 [Fig. 1]). Considering the vaccination groups in an inter-group comparison at the pre-specified time points, significant differences in the anti-S antibody concentrations can be identified (Figure 2 [Fig. 2]): After homologous basic immunization with ChAdOx-1 (cohort AA-12), the lowest antibody levels are found compared to all other vaccination cohorts and over the entire period up to boost vaccination (p<0.001 in each group). The groups BB-6 and AB-12 have the highest anti-S levels, with no significant difference between them. Although immunized with the same vaccine combination, the study cohort BB-6, with a three weeks longer vaccination interval between primary and secondary vaccination compared to group BB-3, has statistically higher anti-S levels over the period until the boost vaccination (BB-3 vs BB-6: 3 months after primary vaccination p<0.001; 6 months after primary vaccination: p=0.02). After the BNT boost, anti-S levels increase significantly in all vaccination groups compared to those analyzed immediately before booster (each p<0.001). The antibody levels exceed those after basic immunization in each case. In the inter-group comparison, the anti-S levels of the vaccination groups are almost the same. Only the BB-3 group shows significantly higher anti-S levels in the inter-group comparison four weeks and three months after boost. This group has the longest time interval between the completion of the basic immunization and the boost vaccination. In a post-hoc analysis, the effect of the vaccination interval between the second and boost vaccination on the kinetics of the antibody rise after the boost was then analyzed (Figure 3 [Fig. 3]). For this purpose, a factor was determined for each subject, which set the anti-S concentrations four weeks after boost in relation to the measured value immediately before the booster vaccination. A longer vaccination interval between the second and third vaccination was found to be predictive for higher anti-S antibody levels (Spearman Correlation r=0.51, 95%-CI 0.41 - 0.6, p<0.001).

Summary: In summary, after basic immunization, it is relevant with which vaccine, which vaccine combination and which vaccination interval a vaccination took place. Vaccination groups with a heterologous vaccination schedule (AB-12) and a prolonged vaccination interval between the first and second vaccination (BB-6) show more favorable developments with regard to anti-S levels. As there is a significant decrease in anti-S levels over time in all vaccination groups after the basic vaccination, a boost vaccination is very useful. This increases the antibody levels in all vaccination groups. Especially group AA-12, which initially had the lowest anti-S RBD levels, benefits. There is no longer any significant difference between the groups. Only BB-3 shows slightly higher antibody levels, which may be related to the longest vaccination interval between completion of the basic immunization and boost vaccination. This vaccination interval correlated well with the antibody kinetics after boost vaccination. In this respect, a longer vaccination interval seems to be particularly immunogenic.


References

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