Correlation of neutralizing tick-borne encephalitis antibodies with the immune response to yellow fever vaccination

Luppa, Fabian Peter (2024): Correlation of neutralizing tick-borne encephalitis antibodies with the immune response to yellow fever vaccination. Dissertation, LMU München: Medizinische Fakultät

Abstract

Due to global warming and advancing globalization, it is to be feared that flaviviruses will continue to spread. In the near future, this will result in intensified virological and infectiological research into the immune reactions to these viruses. A better understanding of the effects of pre-existing immunity on immune responses following vaccination is of great importance for translational infection research in order to develop more effective immunisation strategies. The Plaque Reduction Neutralization Test (PRNT) remains the methodological tool of choice to measure neutralizing antibody titres against Tick-Borne Encephalitis Virus (TBEV). In the present study, the neutralizing antibody titres against TBEV (NT-TBEV) before and 28 days after vaccination with the Live Attenuated Yellow Fever 17D Vaccine (YF17D) against the Yellow Fever Virus (YFV) were analyzed in comparison to the neutralizing antibody titres against YFV (NT-YFV), measured with the Fluorescence Reduction Neutralization Test (FluoRNT). In addition, the Indirect Immunofluorescence Test (IIFT) was used to test whether cross-reacting antibodies against other flaviviruses were present due to the previous TBE vaccination and how these behaved in comparison to TBE-naïve persons after the yellow fever vaccination. It was shown that the administered yellow fever vaccine YF17D had no influence on pre-existing neutralizing antibody titres against TBE. Similarly, the yellow fever vaccination induced equally strong neutralizing antibody titres against yellow fever in TBE-immunised and TBE-naïve individuals. In addition, increased panflaviviral cross-reactivity in TBE-immunised individuals and the absence of cross-reactivity in TBE-naïve individuals following yellow fever vaccination was demonstrated. This resulted in the need to investigate further specific neutralizing and/or cross-reactive epitopes of flaviviruses. The presented work is an independent part of an article submitted for publication (1), which shows that vaccination against TBE and subsequently against yellow fever do not interfere with each other's robust immune response, but can intensify immunogenicity through antibody-dependent enhancement. The data suggest that yellow fever vaccination induces non-cross-reactive antibodies in flavivirus-naïve individuals, while enhanced cross-reactivities are present in TBE vaccinated individuals due to pre-immunity.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Neutralizing Antibodies, Viral Antibodies, Tick-Borne Encephalitis Virus, Epitopes, Humans, Immunoglobulin G, Yellow Fever Vaccine
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 6. Juni 2024
• 1. Bericht­erstatter:in: Pritsch, Michael