Die DGHM prämiert Veröffentlichungen, die sich durch eine große Anwendungsrelevanz auszeichnen. Für diese Auszeichnung können Publikationen vorgschlagen werden, an denen ein DGHM-Mitglied als Erst- oder LetztautorIn beteiligt ist und die in den vorangegangenen 3 Monaten hochrangig publiziert wurden.
Aktuelles Highlight der Infektionsprävention und Klin. Mikrobiologie
Role of vaccines in competitive displacement between SARS-CoV-2 viruses as revealed by the modeling of surveillance data
Hani E J Kaba# 1 , Nikita Srivastava#1 , Felix Hartkopf2 , Maike Hohberg3 , Josué A Bucio-Garcia1, Martin Misailovski1 , Franz-Christoph Bange4 , Michael Kleines5 , Tim Friede3 , Tim Eckmanns2 , Simone Scheithauer6
doi: 10.1007/s15010-025-02586-w.
Dr. Hani Kaba
Link zum vollständigen Artikel: https://pubmed.ncbi.nlm.nih.gov/40748451/
Abstract:
Purpose
SARS-CoV-2 Omicron onset resulted in the rapid displacement of Delta and subsequent intra-Omicron displacement-events. Evidence of geographical diversity on the dynamics is present between and within countries. Considering Omicron’s immune-evasive potential compared to earlier variants, we investigated whether vaccines have influenced local dominance patterns in Germany.
Methods
We used weekly-binned genomic surveillance-data representing 48 regional outbreaks with as many displacement-events. Displacement occurred when a given variant constituted ≥ 50% of all isolates. We ran mixed-effect models to quantify vaccine-density effects on the time-to-displacement (ttd) and survival analysis to compare displacement-free time-intervals. Finally, we compared antigenic properties between variants, analyzing receptor-binding domain (RBD) epitope mutations and estimating RBD-residues antigenicity in solved S-protein structures.
Results
Analyzing 895,000 isolates, we calculated ttd-intervals for the Omicron-Delta, BA.2-BA.1 and BA.5-BA.2 displacements. Mixed-effect models suggested the more vaccines have been administered, the sooner a displacement occurred, observing stronger effects for vaccines administered in temporal proximity to displacement-events (2–7% shorter intervals for one vaccination per 10 immunity-events). Survival analysis suggested stronger effects for Omicron-Delta than intra-Omicron displacements. In silico analysis of ca. 500 epitopes and 27,000 residues suggested antigenic change-driven selection as a likely explanation.
Conclusion
This is the first indication of vaccines influencing competitive displacement between SARS-CoV-2 species within a single, socio-demographically homogenous healthcare-system. Since Omicron infections resulted in less adverse outcomes than Delta, our results help understanding the success of vaccines in avoiding severe outcomes at population level. This is particularly important for future pandemics with impacts on timeliness and intensity of vaccination campaigns.
Kommentar:
Unsere interdisziplinäre Arbeit beschäftigt sich mit der Fragestellung, wie Impfstoffe den Verlauf der SARS-CoV-2-Pandemie auf Populationsebene verändert und dazu beigetragen haben, schwere Folgen auf Bevölkerungsebene zu vermeiden. Dabei konnte die immunevasive Omicron-Variante die Delta-Variante parallel zum Fortschreiten der deutschen Impfkampagne verdrängen.
In Deutschland war Delta zum Zeitpunkt des Ausbruchs von Omicron die einzige verbleibende Variante. Die massiven Mutationen im S-Protein von Omicron, insbesondere in der Rezeptorbindungsdomäne (RBD), führten jedoch zum Verlust von Wildtyp-Antigenstrukturen, die in Delta noch konserviert waren. Darüber hinaus führten die Mutationen zu einer allgemeinen Reduktion der immunogenen Eigenschaften, selbst in strukturellen Bereichen die von der Mutation nicht betroffen waren. Dies erklärt die Fähigkeit von Omicron, Immunreaktionen durch Impfstoffe deutlich besser zu umgehen als Delta.
Je mehr Impfstoffe (die auf den ursprünglichen Wildtyp-Stamm abzielten) in der Bevölkerung verabreicht wurden, desto schneller wurde Delta durch Omicron verdrängt. Dies bestätigen unsere mathematischen Modelle (log-linear mixed-effect models). Zu einem späteren Zeitpunkt verschwand Delta komplett aus dem Infektionspool innerhalb der Bevölkerung und Omicron etablierte sich als einzige SARS-CoV-2 Variantenfamilie. Dies bedeutet, dass die Impfstoffe die Konkurrenzverdrängung zwischen den Varianten beeinflussten haben, was eine neue Erkenntnis darstellt.
Da Infektionen mit Omicron generell weniger negative Folgen hatten als Infektionen mit Delta, helfen diese neuen Ergebnisse, den Erfolg von Impfstoffen bei der Vermeidung schwerer Verläufe auf Bevölkerungsebene besser zu verstehen. Dies ist besonders wichtig für zukünftige Pandemien, da sich dies auf den Zeitpunkt und den Umfang von Impfkampagnen auswirkt.
Kontakt:
Universitätsmedizin Göttingen
Institut für Hygiene und Infektiologie (IH&I)
Robert-Koch-Straße 40
37075 Göttingen
Email:
hani_kaba@med.uni-goettingen.de
nikita.srivastava@med.uni-goettingen.de
Autor:inneninformationen:
1 Department of Infection Control and Infectious Diseases (IH&I), University Medical Center Göttingen (UMG), Göttingen, Germany.
2 Robert Koch Institute (RKI), Berlin, Germany.
3 Department of Medical Statistics, University Medical Center Göttingen (UMG), Göttingen, Germany.
4 Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School (MHH), Hannover, Germany.
5 Laboratory Diagnostic Center, University Hospital RWTH Aachen, Aachen, Germany.
6 Department of Infection Control and Infectious Diseases (IH&I), University Medical Center Göttingen (UMG), Göttingen, Germany. krankenhaushygiene.leitung@med.uni-goettingen.de.
Frühere Highlights
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Link zum vollständigen Artikel: https://pubmed.ncbi.nlm.nih.gov/40511474/
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Link zum vollständigen Artikel: https://pubmed.ncbi.nlm.nih.gov/34929232/
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Candidates
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Link zum vollständigen Artikel: https://pubmed.ncbi.nlm.nih.gov/34515783/
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(*are joint first authors)
Clinical Microbiology and Infection 202. Mar;27(3):473.e1-473.e4.
Link zum vollständigen Artikel: pubmed.ncbi.nlm.nih.gov/33285279/
“A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition”
Stefan E. Heiden*, Nils-Olaf Hübner*, Jürgen A. Bohnert, Claus-Dieter Heidecke, Axel Kramer, Veronika Balau, Wolfgang Gierer, Stephan Schaefer, Tim Eckmanns, Sören Gatermann, Elias Eger, Sebastian Guenther, Karsten Becker & Katharina Schaufler#
Genome Medicine, 2020, 12:113
Link zum vollständigen Artikel: pubmed.ncbi.nlm.nih.gov/33298160/