Elsevier

Vaccine

Volume 27, Issue 10, 4 March 2009, Pages 1628-1636
Vaccine

Immunological responses to pneumococcal vaccine in frail older people

https://doi.org/10.1016/j.vaccine.2008.11.098Get rights and content

Abstract

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.

Aim

To evaluate the immunogenicity of the 7-valent conjugated pneumococcal vaccine (PCV7) versus 23-valent polysaccharide vaccine (23vPPV) and compare the immune response to four serotypes (4, 6B, 18C and 19F), with respect to age or frailty in an elderly population of previously unvaccinated hospitalized patients.

Method

241 patients aged 60 years and over, recruited between 16 May 2005 and 20 February 2006, were randomised to 23PPV or PCV7 vaccine. We measured Frailty Index (FI), Barthel index and the MiniMental State. Serotype-specific IgG was measured by ELISA at base line and 6 months after vaccination. Antibody responses were defined by the ratio of post-vaccination to pre-vaccination IgG antibody concentration (poor < 2-fold increase, acceptable  2.0 to 3.99-fold and strong  4.0-fold increase).

Results

Pre-immunization IgG was generally low and did not differ significantly by age or frailty. Post-immunization, IgG increased to all four serotypes; acceptable or strong response ranged between 29% for (6B) and 57% for (18C). There was no significant difference between the two vaccine types (23PPV versus PCV7). At 6 months post-vaccination, the highest geometric mean IgG concentrations (GMCs) were seen for serotype 19F and the lowest for serotype 4. Although there was some variation by serotype, responses after vaccination were lowest in the most frail or aged subjects.

Conclusions

Pneumococcal vaccines are perceived to offer low protection in the frail elderly, but our study showed that the proportion of this vulnerable population with acceptable responses is encouraging. Frailty, as measured by the Frailty Index, appears to be a better predictor of immune response to pneumococcal vaccines than age alone.

Introduction

The average life expectancy of individuals in developed countries is steadily increasing and this trend is expected to continue increasing with continuing improvements in health care, nutrition and disease prevention. Presently, approximately 13% of the Australian population is aged 65 years and over, projected to increase to over one-quarter by 2051 [1]. Globally, the proportion of the population over 65 years is estimated to reach 21% by 2050 [1]. This shift in population age structure will require an increasing focus on health problems experienced disproportionately by older adults, including certain infectious diseases. Among the most important of these is pneumonia and invasive disease resulting from Streptococcus pneumoniae infection. In developed countries, the annual incidence of invasive pneumococcal disease (IPD) has been estimated at greater than 50 per 100,000 for adults aged 65 years and older [2], [3], who represent a high-risk group, with high morbidity and case mortality which may exceed 50% [4].

Ageing has been associated with a wide range of defects in both innate and adaptive immune system including diminished clonal expansions of B- and T-cells that limit immunological repertoire and are associated with diminished specific antibody responses [5]. Although the decreased capacity of the elderly immune system to respond to new pathogens is likely to reduce the efficacy of most or all vaccines in this population, the evidence for protection of older persons by pneumococcal vaccines is conflicting. Three recent studies illustrate this. One study in a large retrospective cohort study of adults >65 confirmed the efficacy of 23vPPV in preventing bacteremia, but no effect on inpatient or outpatient pneumonia [6]. In contrast, two cohort studies, retrospective and prospective, found decreased rates pneumonia, whether or not associated with bacteremia [7], attributable to 23vPPVvaccination [8]. Because young children do not respond effectively to pneumococcal polysaccharide antigens [9], a 7-valent polysaccharide-protein conjugate vaccine (PCV7) has been recommended for children under 2 years of age [10], [11] that, unlike 23vPPV, induces T-cells to stimulate B-cell development into antibody-producing or memory cells [4]. Because PCV7 prevents pneumonia in young children [11], there is interest in ascertaining whether PCV7 might offer an advantage over 23vPPV in adults. In one study of elderly people who had been previously vaccinated with 23vPPV, a booster dose of PCV7 appeared to be better than a booster does of 23vPPV [12]. Further, the conjugate vaccine has been shown to be effective against invasive disease in children [13] but more clinical research is needed for primary vaccine immunogenicity of conjugate vaccines in adults [14].

Chronological age may not be the best measure of overall vulnerability to disease in the elderly. Though there is considerable disagreement on operational definitions [15], [16], [17], [18], the concept of frailty has evolved to signify “a multidimensional syndrome of loss of reserves (energy, physical ability, cognition, health) that gives rise to vulnerability” [19]. Used in this way, frailty has been shown in various conceptualizations to correlate with a wide range of morbid conditions, including psychiatric illness, obesity and cataract as well as all-cause hospitalization, disability and mortality [20], [21], [22], [23]. The deficit-based Frailty Index (FI) developed by Rockwood et al. has gained support as a measurement tool, and has been validated in various contexts [24]. The essence of this approach is that frailty can be defined as an accumulation of age-related adverse changes, or deficits, in a range of functional systems [25].

We hypothesised that age may not be the only predictor of decline of immune function, but that frailty may also provide such a measure. We evaluated this in the specific context of response to pneumococcal vaccines.

Section snippets

Aim

To evaluate the immunogenicity of the PCV7 versus 23-valent polysaccharide vaccine (23vPPV) and compare the immune response to four serotypes (4, 6B, 18C and 19F), with respect to age or frailty in an elderly population of previously unvaccinated hospitalized patients.

Methods

We conducted a randomized, controlled clinical trial (RCT) specifically targeting frail older people aged ≥60 years who received follow-up care in the Geriatric, cardiology, rheumatology and orthopaedic Departments of a large 800-bed tertiary referral hospital in Sydney, Australia. The hospital is located in the west of Sydney, serves as a tertiary referral base for the western metropolitan area and also acts as the district hospital for the immediately surrounding community. The population

Measurement of pneumococcal antibodies

The prevalence of antibody to PPS were studied using ELISA designed according to the consensus protocol [29], [30] with minor modifications. Serotypes 4, 6B, 18C and 19F were tested as they are in both vaccines (PCV7 and 23PPV).

All serum samples (both pre and post vaccination) were pre-absorbed with purified pneumococcal cell wall polysaccharide (C-PS) (Serum Statens Institute) and a capsular preparation from 22F [29], [30] and antibody concentrations were determined for each sample using three

Interpretation of antibody response

Currently there are no guidelines for the interpretation of the results generated with the serotype-specific assay. No international standard is available; hence antibody responses have been reported in a variety of ways (antibody fold increase, antibody concentration (geometric mean concentration GMC), threshold antibody level or antibody function). These differences have added to the complexity of comparing and interpreting studies [32]. A threshold value (0.35 μg/ml) has been derived from

Analyses

Differences in log-transformed concentrations of capsule specific IgG antibodies between pre and post vaccination sera of both groups were calculated. The differences between groups in IgG increases and fold increases were determined by two-tailed Fisher exact and Pearson Chi-squared tests. The p-values were two-tailed and the level of significance was set at p  0.05. We used of the Statistical Software SPSS V15 (SPSS, Inc. Chicago, IL). The immunogenicity data for 23PPV and PCV7 are summarized

Results

We recruited 241 patients admitted to the hospital between 16 May 2005 and 20 February 2006 to a pneumococcal vaccine trial [34]. Of whom 119 received 23PPV and 122 PCV7. Patient characteristics were evenly distributed between the arms as shown in (Table 1), except the proportion scoring poorly on MiniMental state. The Frailty Index (FI) results (Table 1) showed that all subjects achieved at least one item, with a wide spread of scores from 1 to 24.

The total pre and post vaccination IgG

Discussion

Pneumococcal disease presents a serious risk of morbidity and mortality in the elderly due to the declining immune response with increasing age [35], [36]. This limits the efficacy of vaccines. Reports of the diminished vaccine efficacy in the elderly may reflect either poor functionality of vaccine induced anti-PPS specific antibodies (or inconsistent antibody measurements). Subsequently, there are doubts amongst physicians about the efficacy of pneumococcal vaccine in the elderly [37], [38].

References (43)

  • R.D. Kovaiou et al.

    Age-related changes in immunity: implications for vaccination in the elderly

    Expert Rev Mol Med

    (2007)
  • L.A. Jackson et al.

    Effectiveness of pneumococcal polysaccharide vaccine in older adults

    N Engl J Med

    (2003)
  • A. Vila-Corcoles et al.

    Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study

    Clin Infect Dis

    (2006)
  • F. Ansaldi et al.

    Effectiveness of a 23-valent polysaccharide vaccine in preventing pneumonia and non-invasive pneumococcal infection in elderly people: a large-scale retrospective cohort study

    J Int Med Res

    (2005)
  • R.M. Douglas et al.

    Vaccination against streptococcus pneumoniae in childhood: lack of demonstrable benefit in young Australian children

    J Infect Dis

    (1984)
  • P. Karma et al.

    Efficacy of pneumococcal vaccination against recurrent otitis media. Preliminary results of a field trial in Finland

    Ann Otol Rhinol Laryngol

    (1980)
  • S. Black et al.

    Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children

    Pediatr Infect Dis J

    (2000)
  • A. Ortqvist et al.

    Streptococcus pneumoniae: epidemiology, risk factors, and clinical features

    Semin Resp Crit Care Med

    (2005)
  • A.S. Artz et al.

    Pneumococcal vaccination and revaccination of older adults

    Clin Microbiol Rev

    (2003)
  • W.M. Bortz

    A conceptual framework of frailty: a review

    J Gerontol A: Biol Sci Med Sci

    (2002)
  • L.P. Fried et al.

    Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care

    J Gerontol A: Biol Sci Med Sci

    (2004)
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