Characterization of immune mechanisms in measles and other infectious diseases

Rationale: In addition to the presence of antibodies, cell mediated immunity (CMI) plays an important role in the protection against viruses and bacterial pathogens. In general, humoral immune responses prevent infection by killing the microorganism, whereas CMI prevents disease. Both responses are required for protection against infectious diseases.
CMI involves multiple T lymphocyte (T-cell) populations of the adaptive immune system, with unique antigen specificities and functions such as CD8+ cytotoxic T-cells and CD4+ helper T-cells, also involved in helping antibody production. Both humoral and CMI mechanisms of the adaptive immune response can be acquired through natural infection or exposure to components of pathogens by vaccination. Not only direct effector mechanisms are then primed but also base levels of memory cells recalling specific antigens. These memory cells are there to rapidly and more effectively respond to renewed encounters with the pathogen, which is the mechanism behind vaccination. However, after an initial sharp rise of these responses post-encounter, a period of gradual waning follows. Studying characteristics of disease specific serological and CMI mechanisms in cases versus healthy controls of various age groups in early and late phase after infection is important to unravel life-spanning hallmarks of protection and waning immunity. In cases with a vaccination history, the type of humoral response may for example allow to distinguish between primary and secondary immune (vaccine) failure. These kinds of studies provide important information for future vaccination strategies and offer the opportunity to asses shared or unique immune responses after natural infection or vaccination, as well as to compare immune responses after infection with different viruses and pathogens.
Objective: The main objective is to assess hallmarks of protective and waning immunity to vaccine preventable and non-preventable viral and bacterial diseases in cases of various age groups and age-matched healthy controls. Secondary objectives are 1) to assess the proportion of cases that are due to primary or to secondary vaccine failure (in the case of measles and mumps), in order to determine if waning immunity is responsible for infection amongst those vaccinated and if additional steps need to be undertaken to prevent the risk of additional cases occurring amongst the vaccinated Dutch population; 2) to identify biomarkers of specific T-cell and B-cell responses for the evaluation of the breadth of the humoral and CMI response immediately, and longitudinally after infection; 3) to compare T-cell and B-cell responses after natural infection with vaccine-induced responses; 4) to relate magnitude, quality and dominance of pathogen specific T-cell responses to the quality of concomitant B-cell responses; 5) to compare T-cell and B-cell responses after natural infection between age-groups; 6) to compare the quality and quantity of humoral responses in serum and saliva; 7) to compare T-cell and B-cell responses after natural infection between different microorganisms; and 8) to assess the level of waning immunity over time, both within-host and cross-sectional.
Study design: Controlled observational, non-therapeutic trial
Study population: Laboratory confirmed infectious disease cases and age-matched controls. Depending on the specific infectious disease of the case, cases and controls can be either vaccinated or unvaccinated. Measles was our first disease of interest, due to the outbreak of Measles in 2013. Vaccine failure results in an elevated number of pertussis infections in the last years, the efforts to assess hallmarks of protective and waning immunity are intensified. Therefore, additional cases will be included (in a separate group) for Bordetella pertussis. In addition, we aim to include cases infected with Neisseria meningitidis serogroup B Streptococcus pneumoniae, Mumps Virus, Influenza A Virus and Respiratory Syncytial Virus for immunological evaluation to investigate more divergent mechanisms of protective and waning immunity, and to identify general as well as pathogen specific mechanisms of protection.

To provide important information for future vaccination strategies and offer the opportunity to asses shared or unique immune responses after natural infection or vaccination, as well as to compare immune responses after infection with different viruses and pathogens.

Within 3 months of diagnosis of disease, around 9/12 months after diagnosis (depending on the group), around 18 months after diagnosis, around 36 months after diagnosis. Control group, only one time point.

Not applicable