VITAL at a glance

WP1: the burden of infectious diseases (and their consequences)

WP2. the waning of the immune responsiveness associated with age and other intervening factors

Improving immunity to infections through vaccination in older adults

Background

Vaccination plays a vital role in combating the morbidity and mortality associated with infectious diseases.
Current vaccination programs do not sufficiently protect older adults, leaving them vulnerable to severe illnesses.
Ageing impacts immune responses to vaccination, the exact extend of this impact, variation between individuals and vaccines and how we can predict this remains elusive.

Main objective

Execute a clinical vaccine study to understand the mechanisms underlying vaccine response in different age groups against three different vaccines.

Key findings (I):

A booster vaccination for influenza induced comparable antibody titers in all age groups, whereas lower antibody concentrations were observed in older adults following primary pneumococcal and COVID-19 vaccination as compared to young adults.
A shorter persistence of these antibody responses towards the 6 months timepoint was observed in older adults for all vaccines.
Similarly, in another cohort, we showed that middle-aged adults who have not been previously primed (either through natural exposure or vaccination) exhibited weaker long-term immunity after MenACWY vaccination compared to previously primed adolescents.

Conclusions (I):

Early priming is important in maintaining long-term immunity.
Although the quantity of vaccine-induced antibodies within an individual in the VITAL cohort appears to be vaccine-type specific, a small group of mostly older male adults exhibited low responses to multiple vaccines, suggesting that this group should be the focus of improved vaccination strategies.

Key findings (II):

For the first time, we have evidence that immune cell subsets can be utilized to stratify individuals based on their response to multiple vaccines.
We have identified immune cell subset clusters, which we called immunotypes, that categorize individuals more effectively than age.
Furthermore, when these immunotypes were evaluated in relation to the antibody response to both influenza vaccination as well as multiple vaccines, we identified both good and bad responder immunotypes.
Finally, based on the measurements of immune cell subsets, we have developed a new metric that identifies immune disruption, which could potentially serve as a groundbreaking diagnostic tool for future risk assessment and monitoring.

Conclusion (II):

These findings will enhance our ability to predict who may have a lower response to vaccines and identify pathways that could be targeted for future novel intervention strategies. Current data suggest specific cell types that may be involved in these responses.

Key findings (III):

The project also provides a deeper understanding of frailty and inflammageing (chronic low level inflammation frequently observed in older adults) which could help identify individuals at higher risk of infections, necessitating alternative vaccination strategies.
several of these inflammatory markers are linked to our identified poor responder immunotypes.

Conclusion (III):

A comprehensive analysis that correlates all immune ageing parameters with various vaccine-specific immune responses (including antibody levels, T cell responses, cellular kinetics, and gene expression profiles) will provide a holistic view of factors affecting vaccine response and its key determinants. This information will be crucial in guiding vaccine development and new vaccination strategies for older adults.

Perspective:

The enhanced understanding of immunosenescence that the project has obtained could be pivotal in improving current and future vaccination programs, especially with the advent of new vaccines. It will also aid in the future selection of new adjuvants and in identifying individuals who would benefit from current vaccine strategies to mitigate the issue of immunosenescence.

Links to Key Publications to Date:

WP3. the value of vaccination in older adults

The Value of Vaccines

Background

Vaccination plays a vital role in combating the morbidity and mortality associated with infectious diseases.
Current vaccination programs do not sufficiently protect older adults, leaving them vulnerable to severe illnesses.
This gap in protection results in significant medical expenses and a greater societal burden due to infectious diseases in our rapidly aging populations and therefore more effective vaccination strategies for older adults are urgently needed.

Objectives

WP3 aims to investigate the full economic impact of current ID management and new preventive interventions.
This includes developing economic models to measure and report these impacts convincingly to decision-makers; the economic models consider factors such as frailty level, type of infection, healthcare exposure, place of living and health condition.
These efforts are crucial for improving public health strategies and ensuring effective ID management in ageing populations across Europe.

Some Key Messages/ Findings from Range of Research Studies

Vaccination plays a fundamental role in ensuring healthy aging and preserving quality of life for older adults and efforts should focus on increasing vaccination rates to maximize its benefits.
Maintaining current vaccine coverage rates among older adults is projected to lead to notable increases in for example, influenza, pertussis, HZ, and pneumococcal disease burden over the next several decades due to population aging.
Switching from standard-dose vaccines to higher-dose vaccines not only reduces pressure on hospital capacity but also leads to significant cost savings.
Higher frailty prevalence is strongly associated with lower GDP per capita, especially in the 65–79 age group.
Heterogeneity in contact behaviour is important within the population(s) by age and health conditions as well as the interplay between participants frailty conditions and their contact behaviour.
Current and innovative modelling approaches help to identify strengths, weaknesses, and evidential requirements for decision-making and implementation of immunization programs of ageing adults as well as demonstrating capabilities in for example, quantifying the fiscal impact of infectious disease outbreaks to inform decision-making.

WP1: the burden of infectious diseases (and their consequences)

WP2. the waning of the immune responsiveness associated with age and other intervening factors

Improving immunity to infections through vaccination in older adults

Background

Main objective

Key findings (I):

Conclusions (I):

Key findings (II):

Conclusion (II):

Key findings (III):

Conclusion (III):

Perspective:

Links to Key Publications to Date:

WP3. the value of vaccination in older adults

The Value of Vaccines

Background

Objectives

Some Key Messages/ Findings from Range of Research Studies

Links to Key Publications to Date

WP4. the education/training of key stakeholders on vaccination of older adults