Follow-ups and Analyzing Data

Six months after receiving the pneumococcal conjugate vaccine (PCV13), Work Package 2 (WP2) has started the follow-up with the participants. WP2 is the clinical immunology research domain.

The follow-up planning

As of February 15, the team has initiated the six-month follow-up sampling. The follow-up will be done with all 286 patients who received the PCV13 vaccination between July 13 and October 2, 2020. The six-month follow-up visits of the 40 individuals that were vaccinated in March took place in autumn 2020. The 12 month follow-up for the majority of the participants is planned to start in September 2021.

Data analysis and first results

The team obtained the HI data of the 0 and 1 month time points after flu vaccination. Initial analyses indicate low responsiveness to the flu vaccination in older, middle-aged and young adults (10% against H1N1 and 30-40% towards H3N2). The team is in the process of understanding these data before moving on to subsequent analyses.

An extended analysis was done on baseline immune profiles (cell subsets and inflammatory markers) and cell subset kinetics after vaccination. As plasmablast formation and follicular T cell (cTfc) activation are important for mounting a proper antibody response, the changes in these cell subsets seven days after vaccination was studied. The highest increase in plasmablasts were CD19, CD27 and CD38 molecules in the youngest age group. Though less CD4 cTfc was found in older individuals before vaccination, seven days after vaccination the numbers were increased to the same level as in the other age groups. More detailed analyses are being performed at the moment.

So far, 18 markers have been measured of the inflammageing panel in serum and plasma samples before the influenza vaccination. A low-grade inflammation, often associated with the innate immune system coined inflammageing, is often observed in elderly individuals.  The process is thought to interact with an effective response to pathogens, but likely to vaccine response as well. Of the 18 markers measured so far, 14 are positively correlated to age. Most strongly correlated with age was YKL-40, a protein released by macrophages. An additional set of 10 serum markers is scheduled to be measured. The next step will be to link these markers with vaccine response.

Changes in protocols

A protocol amendment was submitted to the METC to change the planned 12 month follow-up visit into a fingerstick blooddraw, which can be obtained by participants themselves at home and send to the laboratory . Using this method it will be easier for individuals to participate in this sampling moment and thus reduce the number of drop-outs. The METC approved this amendment and all participants have been informed. The 40 early vaccinated individuals will receive the invitation for the 12-month follow-up finger stick blood collection in March/April 2021.

The aim of WP2

WP2 aims to obtain a better insight into changes in the immune response with age, to evaluate the impact of (external) factors on vaccine performance in the aging adults and to formulate evidence-based rationale strategies for improving immunity to infections by vaccination in the ageing population such as vaccinating pre-aging adults.