• Are we prepared for emerging flaviviruses in Europe? Challenges for vaccination.

      Kaaijk, Patricia; Luytjes, Willem (2018-02-01)
      Tick-borne encephalitis and West Nile fever are endemic flavivirus diseases in Europe. Climate change, virus evolution, and social factors may increase the risk of these flavivirus infections and may lead to the emergence of other flaviviruses in Europe that are endemic in (sub)tropical regions of the world. Control of the spread of flaviviruses is very difficult considering the cycling of flaviviruses between arthropod vectors and animal reservoir hosts. The increasing threat of flavivirus infections emphasizes the necessity of a sustainable vector surveillance system, an active animal health surveillance system and an adequate human surveillance system for early detection of flavivirus infections. Vaccination is the most important approach to prevent flavivirus infections. Effective inactivated whole virus vaccines against tick-borne encephalitis (TBE) infection are available. Implementation of TBE vaccination based on favorable cost-effectiveness estimates per region and per target group can reduce the disease burden of TBE infection. At present, several West Nile virus (WNV) vaccine candidates are in various stages of clinical development. A major challenge for WNV vaccine candidates is to demonstrate efficacy, because of the sporadic nature of unpredictable WNV outbreaks. Universal WNV vaccination is unlikely to be cost-effective, vaccination of high-risk groups will be most appropriate to protect against WNV infections.
    • Children and Adults With Mild COVID-19: Dynamics of the Memory T Cell Response up to 10 Months.

      Kaaijk, Patricia; Pimentel, Verónica Olivo; Emmelot, Maarten E; Poelen, Martien; Cevirgel, Alper; Schepp, Rutger M; den Hartog, Gerco; Reukers, Daphne F M; Beckers, Lisa; van Beek, Josine; et al. (2022-02-07)
      Upon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-γ T cell responses in infected children (83%) and adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially in those with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-γ T cell response correlated with S1-SARS-CoV-2-specific serum antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens. Frequencies of SARS-CoV-2-specific T cells were significantly reduced at 10 months after symptom onset, while S1-SARS-CoV-2-specific IgG concentrations were still detectable in 90% of all children and adults.
    • Dynamics of the Antibody Response After a Third Dose of Measles-Mumps-Rubella Vaccine Indicate a Slower Decline Compared With a Second Dose.

      Kaaijk, Patricia; Nicolaie, M Alina; van Rooijen, Debbie; van Houten, Marianne A; van der Klis, Fiona R; Buisman, Anne-Marie; van Binnendijk, Rob S (2020-10-20)
    • Genetic Analysis Reveals Differences in CD8 T Cell Epitope Regions That May Impact Cross-Reactivity of Vaccine-Induced T Cells against Wild-Type Mumps Viruses.

      Kaaijk, Patricia; Emmelot, Maarten E; Kerkhof, Jeroen; van Els, Cécile A C M; Meiring, Hugo D; de Wit, Jelle; Bodewes, Rogier (2021-06-25)
      Nowadays, mumps is re-emerging in highly vaccinated populations. Waning of vaccine-induced immunity plays a role, but antigenic differences between vaccine and mumps outbreak strains could also contribute to reduced vaccine effectiveness. CD8+ T cells play a critical role in immunity to viruses. However, limited data are available about sequence variability in CD8+ T cell epitope regions of mumps virus (MuV) proteins. Recently, the first set of naturally presented human leukocyte antigen Class I (HLA-I) epitopes of MuV was identified by us. In the present study, sequences of 40 CD8+ T cell epitope candidates, including previously and newly identified, obtained from Jeryl-Lynn mumps vaccine strains were compared with genomes from 462 circulating MuV strains. In 31 epitope candidates (78%) amino acid differences were detected, and in 17 (43%) of the epitope candidates the corresponding sequences in wild-type strains had reduced predicted HLA-I-binding compared to the vaccine strains. These findings suggest that vaccinated persons may have reduced T cell immunity to circulating mumps viruses due to antigenic differences.
    • The human CD4 T cell response against mumps virus targets a broadly recognized nucleoprotein epitope.

      de Wit, Jelle; Emmelot, Maarten E; Poelen, Martien C M; Lanfermeijer, Josien; Han, Wanda G H; van Els, Cécile A C M; Kaaijk, Patricia (2019-01-09)
      Mumps outbreaks among vaccinated young adults stress the need for a better understanding of the mumps virus (MuV)-induced immunity. Antibody responses to MuV are well-characterized, but studies on T cell responses are limited. We recently isolated a MuV-specific CD4
    • Identification of naturally processed mumps virus epitopes by mass spectrometry: Confirmation of multiple CD8+ T cell responses in mumps patients.

      de Wit, Jelle; Emmelot, Maarten E; Meiring, Hugo; van Gaans-van den Brink, Jacqueline A M; van Els, Cécile A C M; Kaaijk, Patricia (2019-09-27)
    • Longitudinal Characterization of the Mumps-Specific HLA-A2 Restricted T-Cell Response after Mumps Virus Infection.

      Lanfermeijer, Josien; Nühn, Marieke M; Emmelot, Maarten E; Poelen, Martien C M; van Els, Cécile A C M; Borghans, José A M; van Baarle, Debbie; Kaaijk, Patricia; de Wit, Jelle (2021-12-03)
      Waning of the mumps virus (MuV)-specific humoral response after vaccination has been suggested as a cause for recent mumps outbreaks in vaccinated young adults, although it cannot explain all cases. Moreover, CD8+ T cells may play an important role in the response against MuV; however, little is known about the characteristics and dynamics of the MuV-specific CD8+ T-cell response after MuV infection. Here, we had the opportunity to follow the CD8+ T-cell response to three recently identified HLA-A2*02:01-restricted MuV-specific epitopes from 1.5 to 36 months post-MuV infection in five previously vaccinated and three unvaccinated individuals. The infection-induced CD8+ T-cell response was dominated by T cells specific for the ALDQTDIRV and LLDSSTTRV epitopes, while the response to the GLMEGQIVSV epitope was subdominant. MuV-specific CD8+ T-cell frequencies in the blood declined between 1.5 and 9 months after infection. This decline was not explained by changes in the expression of inhibitory receptors or homing markers. Despite the ongoing changes in the frequencies and phenotype of MuV-specific CD8+ T cells, TCRβ analyses revealed a stable MuV-specific T-cell repertoire over time. These insights in the maintenance of the cellular response against mumps may provide hallmarks for optimizing vaccination strategies towards a long-term cellular memory response.
    • Mumps infection but not childhood vaccination induces persistent polyfunctional CD8+ T-cell memory.

      de Wit, Jelle; Emmelot, Maarten E; Poelen, Martien C M; van Binnendijk, Rob S; van der Lee, Saskia; van Baarle, Debbie; Han, Wanda G H; van Els, Cécile A C M; Kaaijk, Patricia (2018-01-12)
    • Nationwide seroprevalence of SARS-CoV-2 and identification of risk factors in the general population of the Netherlands during the first epidemic wave.

      Vos, Eric R A; den Hartog, Gerco; Schepp, Rutger M; Kaaijk, Patricia; van Vliet, Jeffrey; Helm, Kina; Smits, Gaby; Wijmenga-Monsuur, Alienke; Verberk, Janneke D M; van Boven, Michiel; et al. (2020-11-28)
    • Novel mumps virus epitopes reveal robust cytotoxic T cell responses after natural infection but not after vaccination.

      Kaaijk, Patricia; Emmelot, Maarten E; Meiring, Hugo D; van Els, Cécile A C M; de Wit, Jelle (2021-07-01)
      Mumps is nowadays re-emerging despite vaccination. The contribution of T cell immunity to protection against mumps has not been clearly defined. Previously, we described a set of 41 peptides that were eluted from human leukocyte antigen (HLA) class I molecules of mumps virus (MuV)-infected cells. Here, we confirmed immunogenicity of five novel HLA-B*07:02- and HLA-A*01:01-restricted MuV T cell epitopes from this set of peptides. High frequencies of T cells against these five MuV epitopes could be detected ex vivo in all tested mumps patients. Moreover, these epitope-specific T cells derived from mumps patients displayed strong cytotoxic activity. In contrast, only marginal T cell responses against these novel MuV epitopes could be detected in recently vaccinated persons, corroborating earlier findings. Identifying which MuV epitopes are dominantly targeted in the mumps-specific CD8+ T- response is an important step towards better understanding in the discrepancies between natural infection or vaccination-induced cell-mediated immune protection.
    • A Third Dose of Measles-Mumps-Rubella Vaccine to Improve Immunity Against Mumps in Young Adults.

      Kaaijk, Patricia; Wijmenga-Monsuur, Alienke J; van Houten, Marlies A; Veldhuijzen, Irene K; Ten Hulscher, Hinke I; Kerkhof, Jeroen; van der Klis, Fiona R; van Binnendijk, Rob S (2019-04-23)