Anti-protein immunoglobulin M responses to pneumococcus are not associated with aging

Abstract

Background: The incidence of community-acquired pneumonia and lower respiratory tract infection rises considerably in later life. Immunoglobulin M (IgM) antibody levels to pneumococcal capsular polysaccharide are known to decrease with age; however, whether levels of IgM antibody to pneumococcal proteins are subject to the same decline has not yet been investigated.

Methods: This study measured serum levels and binding capacity of IgM antibody specific to the pneumococcal surface protein A (PspA) and an unencapsulated pneumococcal strain in serum isolated from hospital patients aged < 60 and ≥ 60, with and without lower respiratory tract infection. A group of young healthy volunteers was used as a comparator to represent adults at very low risk of pneumococcal pneumonia. IgM serum antibody levels were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry was performed to assess IgM binding capacity. Linear regression and one-way analysis of variance (ANOVA) tests were used to analyse the results.

Results: Levels and binding capacity of IgM antibody to PspA and the unencapsulated pneumococcal strain were unchanged with age.

Conclusions: These findings suggest that protein-based pneumococcal vaccines may provide protective immunity in the elderly.

Trial registration: The LRTI trial (LRTI and control groups) was approved by the National Health Service Research Ethics Committee in October 2013 (12/NW/0713). Recruitment opened in January 2013 and was completed in July 2013. Healthy volunteer samples were taken from the EHPC dose-ranging and reproducibility trial, approved by the same Research Ethics Committee in October 2011 (11/NW/0592). Recruitment for this study ran from October 2011 until December 2012. LRTI trial: (NCT01861184), EHPC dose-ranging and reproducibility trial: (ISRCTN85403723).

Keywords: IgM antibodies; Immune senescence; Pneumococcus; Proteins; Vaccines.

Conflict of interest statement

The samples used for these experiments were taken from volunteers participating in studies approved by the North West-Liverpool East Research Ethics Committee (12/NW/0713 for LRTI and Control groups; 11/NW/0592 for the Healthy group). All studies were conducted in compliance with the Declaration of Helsinki and informed consent was gained prior to all samples being obtained.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Levels of IgM in relation to age. Levels of (a) total IgM, (b) IgM to the unencapsulated D39-ΔD pneumococcus and to the (c) Pneumococcal Surface Protein A (PspA4) were plotted against volunteer age. Correlations were analysed using linear regression analysis

Fig. 2

Levels of IgM in relation to LRTI. The level of total IgM was examined for patients with LRTI, hospital Controls and a young cohort of Healthy volunteers. Levels of (a) total IgM, (b) IgM to the unencapsulated D39-ΔD pneumococcus and to the (c) Pneumococcal Surface Protein A (PspA4) are shown. Mean values ± SD are shown. * p < 0.05 using ANOVA with Bonferroni’s correction

Fig. 3

Flow cytometric assessment of IgM binding to pneumococcus surface. Pooled sera from different volunteer groups were added to bacteria. Two experiments using different dilutions (1:2 and 1:20) of sera were performed. a Histogram of surface binding of IgM to intact pneumococcus D39-D∆. b Surface binding of IgM from pooled serum samples expressed as the percentage of the bacterial population positive for IgM deposition multiplied by the geometric mean fluorescence of the bacterial population positive for IgM