Download Immune Responses in the Elderly

Ageing and Immunity: implications
for vaccine responsiveness
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Dr Mansel Haeney
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Consultant Immunologist
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Salford Royal NHS FT
Invasive Pneumococcal Infection
England & Wales
Incidence per 100,000 by age group, 2000
80
60
40
20
0
<1 m
1 - 11 m
1-4y
5-9 y
10 - 14 y 15 - 44 y
45 - 64 y
65 - 74 y
> 75 y
from Dr Robert George, RSIL, HPA
West Nile virus epidemic – USA 2002
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> 4 000 cases
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284 deaths
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Median age deceased = 78yr
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O`Leary et al 2004
Thymic involution
Cellular Immunity in the Elderly
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Altered T cell phenotype
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 naïve T cells;  memory T cells
 Reduced T cell responses
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response to TCR stimulation
T cell proliferation
expression of IL2-R
IL2 production
Ginaldi et al 1999
Immune Risk Phenotype
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Longitudinal immunological study to establish
predictive factors of longevity
OCTA / NONA study ( Wikby et al)
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Immune risk phenotype
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CD4:CD8 ratio < 1.00
 CD8+ CD28- cells
 CD8+ CD28- CD27- in very old
 B cells
Poor in vitro T cell proliferation
CMV seropositivity
Innate immunity
Natural ; non-specific
Responses of the
elderly to
immunisation
Fig. 2. Serum concentrations of anti-KLH IgM (A) and IgG (B) were assessed in young and
older physically active and sedentary men after KLH immunization
Smith, T. P. et al. J Appl Physiol 97: 491-498 2004;
doi:10.1152/japplphysiol.01404.2003
Copyright ©2004 American Physiological Society
Pneumococcal antibody production
1.
Low pre – and post – immunization titres
2.
Reduced frequency of 2 x increase in titre
3.
4.
Reduced frequency of ‘protective’ ab.
titres at 1 month
Rapid decline in ab. titres by 1 year
JCVI/mins-pneumococcal-220108
What can be done
to better protect
the elderly?
Reversal of Thymic Atrophy
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Surgical or chemical castration ( in mice)
alters TREC levels
Chemical castration improves TREC levels
in humans
IL-7 reverses thymic atrophy in older
animals – role of fusion protein CCR9-IL7?
Effect of CMV infection on immune
function in the elderly?
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Viral infection normally cleared by CD8+ virus-specific T
cells
Up to 50% CD8+ T cells in elderly reported to be CMVspecific : may lead to impaired responsiveness to other
viral infections in elderly people
KLRG-1 is a marker of senescence: KLRG-1 + T cells do
not proliferate in vitro
96% CMV+ CD8+ T cells expressed KLRG-1
In elderly, fewer CMV+ CD8+ T cells secreted IFNγ
compared with cells from younger people
Does immunological senescence negate
the benefits of immunisation?
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Prospective cohort study 25,000
independently living people : 50%
reduction in mortality
Repeated immunisation seems
advantageous
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1st immunisation : 9% reduction in mortality
2nd/repeat immunisation: 75% reduction
Does immunological senescence negate
the benefits of immunisation?
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200 hospitalised elderly patients with
proven influenza: 61% had received
influenza vaccine
Influenza epidemics: hospitalisation of
elderly lags 2 weeks behind peak in
community. Are children `the engine that
drives the epidemic?`
Epidemic influenza
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Elderly have greatest risk of mortality
Children responsible for most transmission
Immunisation of children reduces infection rate
in children, adults and elderly
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Predictions suggest vaccination of 30% schoolchildren should
reduce spread from 90% to 65%
Vaccination of 70% children should reduce spread to 4%
Herd immunity may provide cost-effective
protection of elderly
(Reichert, NEJM,2001; Cohen, Science, 2004)
Impact of PCV vaccination
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USA data:
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94% fall in invasive pneumococcal disease
caused by 7 serotypes in children < 5yrs
62% fall in IPD in individuals > 5yrs who had
NOT been immunised
Implies elderly may benefit more from `herd
immunity` effect of childhood PCV
programme than from PPV immunisation
Confounding variables
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Pace of ageing
Spectrum of `youngold (>65y) to
extremely old (>95y)
Survivor bias
Institutionalisation
Physical fitness
Conclusions
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Immunosenescent changes particularly affect T
cell populations and function
Immunosenescence affects the response to
vaccines
Vaccine-induced antibody responses wane
rapidly in the elderly
Better vaccine efficacy in the elderly may require
(i) improved immune responsiveness and (ii)
changes to vaccine formulation
Herd immunity applies to the elderly as well as
to the young
You can live to be a hundred
You can live to be a hundred
if you give up all the things that make
you want to live to be a hundred
Woody Allen