Presentation on theme: "Immunizations in the Older Adult WAO 2011 Monroe James King, DO, FAAAAI Division of Allergy and Immunology University of South Florida, USA."— Presentation transcript:
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.
Endocrine Senescence Cytokine Imbalance Autoantibody Paraproteinemia CHRONIC, LOW-LEVEL INFLAMMATION Cytokine Imbalance Autoantibody Immune or Inflammatory Dysregulation Genetic Factors Chronic Ag Exposure Genetic Factors ? Replicative Senescence Thymic Involution Qualitative T Cell Defects Accumulation of Memory Cells, Fewer Naïve Cells MILD TO MODERATE IMMUNEDEFICIENCY Environmental Factors, ROS
Aging Heterogeneity Frailty 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 T- cell 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 5 th 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 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 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 5 th cranial nerve Post herpetic neuralgia may be severe.
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: 59:171- 1716