Vaccine immunogenicity in Dutch frail versus non-frail older individuals

With ageing there is a decline in the functioning of the immune system, making
older people more vulnerable for infections and resulting in a smaller boost of
the immune system in response to vaccination. Since there is great
heterogeneity in the rate at which immune function declines, it is important to
identify elderly at risk for low vaccination responses and thus at higher risk
for infection. We hypothesize that frailty in older individuals might underly
low responses to the 23-valent polysaccharide pneumococcal vaccination (PPV23)
that will be implemented in the National immunization program in autumn this
year for elderly 73-79 years of age and to the SARS-CoV-2 vaccines that will be
offered during 2021.
To study this hypothesis, we will capitalize on the infrastructure and data
provided by the ongoing longitudinal Doetinchem Cohort Study (DCS)
(NL63779.041.17), which includes available frailty data of all participants, to
assess the immune response to PPV23 and the yearly Influenza vaccine in
relation to frailty. In the DCS, persons originally 20-59 years of age at study
start, have been followed for over 30 years (N>3700). Various frailty
parameters have been assessed in these participants. Based on these, a frailty
score (index) has been determined by using the most recent information on 36
frailty-related *health deficits*, i.e. specific (co)morbidities, tests of
physical (dys)functioning and cognition. Because of these data the DCS provides
a unique opportunity to get insight into factors contributing to vaccine
immunogenicity in older persons. Recent data from a sub-cohort of the DCS aged
60-80 years revealed that lingering inflammation is associated with frailty.
Therefore frailty may be linked to reduced immune function and vaccination
responses.

The primary objective is to compare antibody responses against the pneumococcal
vaccine strains and Influenza virus vaccine types in blood and saliva of older
individuals with respect to frailty, taking sex differences into account. The
overall aim is to address which specific pre-vaccination frailty
characteristics and immunological parameters are associated with low or high
vaccination responses. Using state of the art statistical analyses, we aim to
identify frailty-associated biomarker profiles predicting increased risk of
diminished vaccine responses. Altogether, early recognition of frailty or
unfavorable 'biological ageing' based on immune markers may be useful in
conceiving individualized approaches for improved vaccination strategies or
alternative interventions earlier in life to prevent immune frailty at older
age. This will contribute to healthy ageing and long-term participation of
older individuals in society.

Longitudinal observational study

The burden associated with participation involves collection of blood samples
by venipuncture (pre vaccination 16-45 ml and 3 times post vaccination 16 ml
per visit), and saliva samples (3 times). In addition, the subject will be
asked to fill in a small questionnaire (2 times). In case of an additional
SARS-CoV-2 booster dose, participation also involves up to a maximum of 2
additional venipuncture blood samples, 2 additional finger prick blood sample,
2 additional nose (or saliva) fluids samples and 4 additional questionnaires
per vaccination. Depending on the time between vaccinations, one or more time
points may expire or are pushed forward.

Participants will be asked to visit the GGD location or, if needed, will be
visited at home. The potential risks are considered minimal. The results of the
study may contribute to a better control of respiratory diseases in older frail
persons.