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Introduction: Tick-borne encephalitis virus (TBEV) is one of the most relevant tick-transmitted neurotropic arboviruses in Europe and Asia and the causative agent of tick-borne encephalitis (TBE). Annually more than 10,000 TBE cases are reported despite having vaccines available. In Europe, the vaccines FSME-IMMUN® and Encepur® based on formaldehyde-inactivated whole viruses are licensed. However, demanding vaccination schedules contribute to sub-optimal vaccination uptake and breakthrough infections have been reported repeatedly. Due to its immunogenic properties as well as its role in viral replication and disease pathogenesis, the non-structural protein 1 (NS1) of flaviviruses has become of interest for non-virion based flavivirus vaccine candidates in recent years., Methods: Therefore, immunogenicity and protective efficacy of TBEV NS1 expressed by neuraminidase (NA)-deficient Influenza A virus (IAV) or Modified Vaccinia virus Ankara (MVA) vectors were investigated in this study., Results: With these recombinant viral vectors TBEV NS1-specific antibody and T cell responses were induced. Upon heterologous prime/boost regimens partial protection against lethal TBEV challenge infection was afforded in mice., Discussion: This supports the inclusion of NS1 as a vaccine component in next generation TBEV vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Beicht, Kubinski, Zdora, Puff, Biermann, Gerlach, Baumgärtner, Sutter, Osterhaus, Prajeeth and Rimmelzwaan.)

Introduction: The emergency use of vaccines has been the most efficient way to control the coronavirus disease 19 (COVID-19) pandemic. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is the main target for virus neutralizing (VN) antibodies., Methods: A SARS-CoV-2 RBD vaccine candidate was produced in the Thermothelomyces heterothallica (formerly, Myceliophthora thermophila) C1 protein expression system and coupled to a nanoparticle. Immunogenicity and efficacy of this vaccine candidate was tested using the Syrian golden hamster (Mesocricetus auratus) infection model., Results: One dose of 10-μg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies neutralized SARS-CoV-2 variants of concern: D614G, Alpha, Beta, Gamma, and Delta., Discussion: Our results support the use of the Thermothelomyces heterothallica C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections to help overcome limitations associated with the use of mammalian expression system., Competing Interests: Author GA was employed by company Viroclinics Xplore. Authors RT and ME work for the company Dyadic International, Inc., and may use the vaccine for commercial use. Authors B-JB and BH filed a patent application on coronavirus nanoparticle vaccines. Authors MS, MW, and MV work for the company VTT Technical Research Centre of Finland, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gonzalez-Hernandez, Kaiser, Steffen, Ciurkiewicz, van Amerongen, Tchelet, Emalfarb, Saloheimo, Wiebe, Vitikainen, Albulescu, Bosch, Baumgärtner, Haagmans and Osterhaus.)

Introduction: Tick-borne encephalitis virus (TBEV) is an important human pathogen that can cause a serious disease involving the central nervous system (tick-borne encephalitis, TBE). Although approved inactivated vaccines are available, the number of TBE cases is rising, and breakthrough infections in fully vaccinated subjects have been reported in recent years., Methods: In the present study, we generated and characterized a recombinant Modified Vaccinia virus Ankara (MVA) for the delivery of the pre-membrane (prM) and envelope (E) proteins of TBEV (MVA-prME)., Results: MVA-prME was tested in mice in comparison with a licensed vaccine FSME-IMMUN® and proved to be highly immunogenic and afforded full protection against challenge infection with TBEV., Discussion: Our data indicate that MVA-prME holds promise as an improved next-generation vaccine for the prevention of TBE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kubinski, Beicht, Zdora, Biermann, Puff, Gerlach, Tscherne, Baumgärtner, Osterhaus, Sutter, Prajeeth and Rimmelzwaan.)

Introduction: Naturally attenuated Langat virus (LGTV) and highly pathogenic tick-borne encephalitis virus (TBEV) share antigenically similar viral proteins and are grouped together in the same flavivirus serocomplex. In the early 1970s, this has encouraged the usage of LGTV as a potential live attenuated vaccine against tick-borne encephalitis (TBE) until cases of encephalitis were reported among vaccinees. Previously, we have shown in a mouse model that immunity induced against LGTV protects mice against lethal TBEV challenge infection. However, the immune correlates of this protection have not been studied., Methods: We used the strategy of adoptive transfer of either serum or T cells from LGTV infected mice into naïve recipient mice and challenged them with lethal dose of TBEV., Results: We show that mouse infection with LGTV induced both cross-reactive antibodies and T cells against TBEV. To identify correlates of protection, Monitoring the disease progression in these mice for 16 days post infection, showed that serum from LGTV infected mice efficiently protected from developing severe disease. On the other hand, adoptive transfer of T cells from LGTV infected mice failed to provide protection. Histopathological investigation of infected brains suggested a possible role of microglia and T cells in inflammatory processes within the brain., Discussion: Our data provide key information regarding the immune correlates of protection induced by LGTV infection of mice which may help design better vaccines against TBEV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kubinski, Beicht, Zdora, Saletti, Kircher, Petry-Gusmag, Steffen, Puff, Jung, Baumgärtner, Rimmelzwaan, Osterhaus and Prajeeth.)

Immunosenescence is a process associated with aging that leads to dysregulation of cells of innate and adaptive immunity, which may become dysfunctional. Consequently, older adults show increased severity of viral and bacterial infections and impaired responses to vaccinations. A better understanding of the process of immunosenescence will aid the development of novel strategies to boost the immune system in older adults. In this review, we focus on major alterations of the immune system triggered by aging, and address the effect of chronic viral infections, effectiveness of vaccination of older adults and strategies to improve immune function in this vulnerable age group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Palacios-Pedrero, Osterhaus, Becker, Elbahesh, Rimmelzwaan and Saletti.)