WP2 aims to obtain a better insight in the immune response with age, to evaluate the impact of (external) factors on vaccine performance in the ageing adults and to formulate evidence-based rationale strategies for improving immunity to infections by vaccination in the ageing population such as vaccinating pr-ageing adults.
Follow-up vaccination study
The 6M follow-up after pneumococcal vaccination sampling has been finalized and finger stick sets for small blood draws for the 12M follow-up sampling, which will take place in September 2021, have been prepared.
Immunological analyses
HI antibody data
Interpretation of HI antibody data after influenza vaccination are ongoing.
Cell Subset Analyses
Analyses of baseline immune cell profiles has identified substantial heterogeneity between individuals, which is only in part explained by age. Therefore the team performed clustering methods based on >200 immune cell parameters. In the immune clusters it was initially identified (see the picture for a clustering method resulting in 9 clusters) and observed there were some young adults exhibiting immune cell signatures resembling older individuals and vice versa. The team aims to use these immune cell profiles to classify individuals (irrespective of age) and correlate to specific clinical phenotypes (comorbidities and frailty associated parameters) and vaccination response.
Serum Biomarkers
Furthermore, the team has measured a panel of markers in serum (28 markers in total, 19 at University Medical Center Groningen and 9 at INSERM Paris) to assess baseline inflammatory state (as a measure of inflammageing). A low-grade inflammation, often associated with the innate immune system, so-called inflammageing, is often observed in elderly individuals. Inflammaging is thought to influence the response to pathogens, but likely also to vaccines. Four different patterns are observed for the markers measured:
- A gradual increase with age (pattern in figure A)
- Middle aged and older adults are different form younger adults (figure B)
- Older adults are different from middle aged and younger adults (figure C)
- No relation to age groups (figure D)
The next step is to relate these inflammation profiles to clinical frailty and vaccination response.
Preparation for Additional Analyses
Furthermore, the team is preparing serum and saliva sample shipments from the National Institute for Public Health and Environment (RIVM), the Netherlands, to Innovative Medicines Initiative (IMI) partners for the analyses of mucosal influenza antibody responses, functional pneumococcal antibody analysis by OPA as well as PBMC shipments for T cell assays.