Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations

University of Alabama at Birmingham, Department of Pathology, Birmingham, AL 35294-2170, USA.
Infection and immunity (Impact Factor: 3.73). 11/2010; 79(1):314-20. DOI: 10.1128/IAI.00768-10
Source: PubMed


Since the 23-valent pneumococcal polysaccharide vaccine (PPV23) is less effective for older adults than for young adults, it is important to investigate the immunologic basis for the reduced efficacy of PPV23 among older adults. We determined the effectiveness of PPV23 among young (n = 55) and older (n = 44) adults by measuring the serum IgG, IgM, and IgA concentrations and opsonic capacities against serotypes 14, 18C, and 23F. While young and older adults showed no difference in levels of IgG antibodies against pneumococcal polysaccharide (PPS), older adults had lower IgA and IgM antibody levels than young adults for all three serotypes. In both age groups, anti-PPS IgA or IgM antibody levels were much lower than anti-PPS IgG antibody levels. Young adults showed higher opsonic capacities than older adults for serotypes 14 and 23F. In order to determine the effects of anti-PPS IgA or IgM antibodies on the functional difference between young and older adults, anti-PPS IgA or IgM antibodies were removed from immune sera by affinity chromatography. The difference in opsonic capacity between young and older adults disappeared for serotypes 14 and 23F (but not for serotype 18C) when IgM antibody was removed. However, there was no significant difference between the two age groups when IgA antibody was removed. In conclusion, even though anti-PPS IgG antibody levels are high compared with anti-PPS IgM antibody levels, the low levels of anti-PPS IgM antibody alone can explain the functional difference observed between young and older adults immunized with PPV23 with regard to some pneumococcal serotypes.


Available from: Saeyoung Park, May 03, 2014
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    • "Vaccine-specific antibodies in older people are quantitatively and qualitatively impaired. For example, anti-pneumococcal polysaccharide (PPS) antibodies have lower opsonophagocytic index and affinity in the elderly than in healthy young adults (Kolibab et al., 2005b; Park and Nahm, 2011). Streptococcus pneumoniae infection is a serious complication secondary to influenza, and together these two diseases comprise a substantial infectious burden for children aged under two, the elderly and immunocompromised individuals (McCullers, 2006). "
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    ABSTRACT: Immune protection against pulmonary infections, such as seasonal flu and invasive pneumonia, is severely attenuated with age, and vaccination regimes for the elderly people often fail to elicit effective immune response. We have previously shown that influenza and pneumococcal vaccine responses in the older population are significantly impaired in terms of serum antibody production, and have shown repertoire differences by CDR-H3 spectratype analysis. Here we report a detailed analysis of the B cell repertoire in response to vaccine, including a breakdown of sequences by class and subclass. Clustering analysis of high-throughput sequencing data enables us to visualize the response in terms of expansions of clonotypes, changes in CDR-H3 characteristics, and somatic hypermutation as well as identifying the commonly used IGH genes. We have highlighted a number of significant age-related changes in the B cell repertoire. Interestingly, in light of the fact that IgG is the most prevalent serum antibody and the most widely used as a correlate of protection, the most striking age-related differences are in the IgA response, with defects also seen in the IgM repertoire. In addition there is a skewing toward IgG2 in the IgG sequences of the older samples at all time points. This analysis illustrates the importance of antibody classes other than IgG and has highlighted a number of areas for future consideration in vaccine studies of the elderly.
    Frontiers in Immunology 07/2012; 3:193. DOI:10.3389/fimmu.2012.00193
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    • "A rise in serum IgG, IgA and IgM was seen in all individuals postimmunisation; however, the time course was different by isotype and varied between the two cohorts. IgG serum responses were similar between young and old, peaking at day 28, consistent with data from other groups (Lee et al., 2010; Park & Nahm, 2011). In contrast, in the young individuals, an early peak IgA serum response was detected at day 7, while in the older cohort, the rise in IgA was more gradual, peaking at day 28 (Fig. 4b). "
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    ABSTRACT: It is well known that older people are more susceptible to morbidity and mortality from infectious diseases, particularly from pulmonary diseases such as pneumococcal pneumonia where vaccines do not provide efficient protection as in younger populations. We have previously shown that the B-cell repertoire in the old is reduced and hypothesise that this may contribute to the impaired humoral responses of the elderly. Here, we investigated the repertoire and antibody responses to winter vaccination in two age groups, aged 18–49 and 65–89. We found that the serum IgM and IgA pneumococcal responses were significantly impaired in the older group, with no difference in IgG levels. IGHM spectratype analysis seems to be the most promising in terms of its predictive ability for vaccine responses. Spectratypes showed a clear change in the repertoire at day 7 after vaccination, with a return to the baseline levels at day 28. The changes at day 7 reflected expansion of IGH sequences that have smaller, more hydrophilic, CDR3 regions, and these changes were attenuated in the older group. The older group was more likely to have spectratypes indicative of a reduced diversity at day 0 and day 28. On average, the baseline repertoire in the older group was comprised of larger CDR3 regions than in the younger group. In conclusion, IgA and IgM responses are significantly impaired in the elderly pneumococcal response and are likely key mediators of protection. Hydrophilicity and/or small size of the IGH CDR3 appear to be important in these responses.
    Aging cell 08/2011; 10(6):922 - 930. DOI:10.1111/j.1474-9726.2011.00732.x · 6.34 Impact Factor
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    ABSTRACT: Vaccinations are powerful tools to help prevent/minimize the consequences of infections. Currently available vaccines are protecting only part of the human population because of the age-related decrease in immune functions. Vac-cination against Streptococcus pneumoniae and influenza are strongly recommended in children under 2 years of age and individuals over 65 years of age to protect them from infection. However, although commercially available vaccines against these infectious diseases provide protection and ensure lasting immunological memory in children and adults, they are much less effective in elderly individuals. The mechanisms for the reduced response of the elderly to pneumococcal and influenza vaccines are discussed in this review from the perspective of deficiencies seen in B cell function with age.
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