Transcript Immunizations in Older Adults_Dec2011

Immunizations in the Older Adult
WAO 2011
Monroe James King, DO, FAAAAI
Division of Allergy and Immunology
University of South Florida, USA
• Our current understanding is that there are genetic,
epigenetic and environmental factors that result in aging.
• Proinflammatory cytokines, particularly IL-6 consistently
found to be elevated in frail elderly.
• These create picture of chronic inflammatory disease
(cachexia, sarcopenia, osteoporosis, etc.).
• Dysregulation of NFkB may be the upstream lesion and the
target for future intervention.
? Replicative
Senescence
Genetic Factors
Environmental
Factors, ROS
Thymic Involution
Endocrine
Senescence
Immune or Inflammatory
Dysregulation
Qualitative
T Cell Defects
Accumulation of
Memory Cells,
Fewer Naïve Cells
Chronic Ag
Exposure
Genetic Factors
Cytokine
Imbalance
MILD TO MODERATE
IMMUNEDEFICIENCY
Autoantibody
Paraproteinemia
CHRONIC, LOW-LEVEL
INFLAMMATION
Aging Heterogeneity
Frailty
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Occurs:
• 7% at age 65
• 40% at age 80
Risk increased with
comorbidities
Impacts physical &
cognitive function
Reduced functional reserve
Susceptibility to stress and
diseases
Predicts negative health
outcomes, including nursing
home placement
Clinical Impact of Immune
Senescence Upon Elderly
Diminished protective response to vaccination
(influenza, pneumococcus)
Increased susceptibility to viral and bacterial infection
Altered response to CMV
Reflects modified CD4+ and CD8+ T-cell repertoire
Chronic heightened pro-inflammatory state
Increase risk auto-immune disease, malignancy,
atherosclerosis
Healthiest elderly forestall immune senescence
Pawelec G. Immunity and ageing in man. Experimental Gerontology 2006; 41: 1239–42
Adaptive Immunity And Aging
T-cells
Progressive involution of thymus does not alter Tcell number, but decreases the T cells ability to
proliferate in response to antigen*
CD4+/CD8+ ratio (BAL) increases with age
Reflects primed T-cells from repeated antigenic
stimulation**
Reduced naïve, increased memory T-cells***
*Sharma G, Goodwin J. Clinical Interventions in Aging 2006; 1(3): 253-60
**Meyer KC et al. Am J Respir Crit Care Med 1996; 153:1072-9.
***Katial R. Clin Chest Med 2007; 28:663-72.
Adaptive Immunity and Aging - 2
B-cells
Decline in total lymphocyte number and response to
phytohemaglutinin*
Antibody production less efficient
Reduced affinity for specific antigens
Decline in somatic hypermutation*
Immunoglobulins in the lung BAL fluid**
Total IgA, IgM, & IgG increase with age.
Increased IL-6 also identified
*Liu J et al. Mech Ageing Dev 2007; 94:177-82.
**Katial R. Clin Chest Med 2007; 28:663-72.
Summary of Age-related Changes in
Adaptive Immunity
• Dendritic cells _ Phagocytosis, pinocytosis, TLR
expression and function, IL6 and TNFα
• T cells - response and proliferation, CD28
expression, TCR diversity, accumulation of
CD8+CD28+ T cells
• B cells – produce low affinity antibodies,
oligoclonal expansion, MHCclass II molecule
expression
Busse&Mathur, JACI 2010
Hypothesized Mechanisms Underlying
Immune Senescence*
• Oligoclonal expansion of inhibitory CD8+ cells
• Age-associated accumulation of inhibitory
proteins on the cell surfaces
• Reduction in telomere length in human
lymphocytes
High _ Workshop on Immunizations in
Older Adults
Vaccines for Older Adults
Influenza
Pneumococcal
Zoster
Influenza
• 5th leading cause of death in people over 50
• Vaccine efficacy in those age 65 or older -23%
Compared to Children 2 or older – 38% *
• Cochrane database review of 31 studies in
adults showed 50-80% efficacy in preventing
influenza illness in healthy adults –no data for
elderly or those with comorbidity.**
* Jefferson T et al,** Jefferson T CDB
Influenza Vaccine
Experimental Efficacy ex vivo
In response to vaccine adults ≥64 adults
compared to age 20-50
• PBMC produce less IFNγ
• Decreased CD8+ cell response
• Frail had even poorer response
Deng et al
Influenza Vaccine Problems
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New strains
Viral drift
Age specific responses
Difficult to measure effectiveness in
populations, age groups and frailty
Possible fixes for Influenza vaccines
• Adjuvants-DNA that encodes a key viral-surface
protein called hemagglutinin (HA) as booster
• Age specific flu vaccine for older patients
High dose Fluzone® has 4 times the dose of
regular Fluzone®
– Produces higher antibody levels
– CDC has not made dosage recommendation
– Also available for intradermal admin.
Pneumococcal Vaccine
• 23 valent polysacharide vaccine
• Recommend once after age 65 (if more than 5 years
since original vaccine)
• CDC does not recommend repeat boosters as may
even increase susceptibility in older adults
• Does antibody response predict protection?
– No difference in patients hospitalized for CAP *
(Spain)
– Some evidence for protection but not age specific
*Manzur et al
Herpes Zoster
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Reactivation of chicken pox virus (Varicella)
A DNA virus, persists in sensory nerve ganglia
1 of 3 persons will develop shingles during lifetime (CDC)
Cell mediated immunity is major determinant of incidence
and severity
• Immunocompromised persons may get disseminated
disease with skin, CNS, pulmonary and hepatic involvement
• Usually unilateral on trunk or 5th cranial nerve
• Post herpetic neuralgia may be severe
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Zoster outbreak
Herpes Zoster Opthalmica
Herpes Zoster
• Associated with:
– Aging
– Immunosuppression
– Intrauterine exposure
– Varicella at younger than 18 months of age
Herpes Zoster Vaccine
• Zoster vaccine changes host-virus relationship
rather than preventing primary infection
• Live virus vaccine boosts cell mediated
immunity
• Reduces frequency and severity of shingles
and burden of illness (pain) in older adults
• Expensive ($161 in US) not covered by
Medicare
• http://www.cdc.gov/shingles/vaccination.html
Herpes Zoster Vaccine Administration
• Age 50 or older
• Less effective within 4 weeks of Pneumovax
Zoster Vaccine
Contraindications and Precautions
• Contraindications:
– Severe allergic reaction to vaccine components
• Gelatin, neomycin,
– Pregnancy
– Immunosuppression and immunodeficiency
– Tuberculosis –active untreated
• Precautions:
– Moderate or severe acute illness
– Current treatment with antiviral drug
– Immune modulators and recombinant human
mediators
Bibliography
• Deng Y et al. Age-related type1 T cell responses to
influenza: reduced activation ex vivo, decreased
expansion in CTI, culture in vitro and blunted
response to influenza vaccine in the elderly. J
Immunol 2004:172:3437-3446Gruver AL, Hudson LL,
Sempowski GD: Immunosenescence of Aging, J of
Pathology 2007:211:144-156
• Hanania NA, King MJ et al: Report of a Workshop on
Asthma in the Elderly, JACI 2011: Supp 3. Sep S4=S22
Bibliography (2)
• Jefferson T et al: Assessment of the efficacy and
effectiveness of influenza vaccines in elderly people a
systematic review. Lancet 2005:336:1165-1174.
• Jefferson T et al. Vaccines for preventing influenza in
health adults. Cochrane database Syst Review. 2007 Apr
18;CD001269
• Manzur A et al: Influence of prior pneumococcal vaccine
on outcomes of older adults with community acquired
pneumonia. J American Geriatric Society 2011: 59:1711716