Elsevier

Vaccine

Volume 30, Issue 27, 8 June 2012, Pages 3983-3985
Vaccine

Brief report
Pneumococcal vaccination may induce anti-oxidized low-density lipoprotein antibodies that have potentially protective effects against cardiovascular disease

https://doi.org/10.1016/j.vaccine.2012.03.084Get rights and content

Abstract

Many animal and human studies have found an inverse association between anti-oxidized low-density lipoprotein (oxLDL) antibodies (anti-oxLDL) and atherosclerotic burden. Furthermore, anti-oxLDL antibodies have been shown to cause regression of atherosclerotic plaque in mice. Animal studies indicate that the 23-valent pneumococcal vaccine may induce the production of these potentially protective anti-oxLDL antibodies, and human epidemiological studies support their potentially beneficial effect in reducing cardiovascular events. Here we describe the association between self-reported pneumococcal vaccination, vaccination verified by linkage to health records, and anti-pneumococcal antibody titers, and anti-ox-LDL titers in a group of 116 older people. We found a bimodal distribution of anti-oxLDL antibodies, and a significant association between pneumococcal IgG and anti-oxLDL antibody titers that remained after multivariate adjustment for potential confounders (p = 0.04). There was no significant association between self-reported vaccination or vaccination verified by health record linkage and ox-LDL titers, which may be due to reporting error or variability in response to the vaccine. These results support a mechanistic link between pneumococcal vaccination and a potential protective effect on cardiovascular disease, and indicate that self-reported or verified vaccine status may not be sufficient to detect this association.

Introduction

Atherosclerosis remains a leading cause of morbidity and mortality in the Western world manifesting as peripheral vascular disease, coronary heart disease and stroke. A major risk factor for developing atherosclerosis is high cholesterol. OxLDL is one of the main cholesterol fractions that accumulates in atherosclerotic plaques, and serum concentrations may correlate with the severity of coronary vascular disease [1], [2].

Antibodies against oxLDL have also been shown to be present in both mice and humans. An inverse association between these anti-oxLDL antibodies and atherosclerotic burden has consistently been shown in mouse models (see review [3]), as well as in humans [4], [5], [6] although results in humans have been more variable [7], [8], [9]. The conflicting data may be due to the release of ox-LDL after plaque rupture and the formation of anti-oxLDL antibodies as an epiphenomenon after acute coronary syndrome (ACS). These antibodies however have been shown to block the uptake of LDL by macrophages and may hinder the development of foam cells [10]; indeed they have been shown to cause the regression of atherosclerotic plaque in mice [10].

Given the potential protective effect of anti-oxLDL antibodies, there has been much interest in harnessing them for immunoprotection against atherosclerosis [11]. Anti-oxLDL antibodies have been shown to be induced by pneumococcal vaccination [10]. This is thought to be secondary to pneumococcal vaccination-induced anti-phosphorylcholine antibodies that cross-react with oxLDL [10].

There are limited data on the association of anti-oxLDL antibodies and pneumococcal vaccination in the clinical setting. A case–control study by Lamontagne et al. [12] showed that cases with myocardial infarction were half as likely as controls to have had pneumococcal vaccination. Unfortunately this study was based on record linkage and was not able to adjust for confounders such as smoking, obesity or socioeconomic status. A prospective study by Tseng et al. [13] showed no association between cardiovascular disease and pneumococcal vaccination in young people with low cardiovascular risk, but did find a trend toward reduced risk of myocardial infarction and stroke in older people (HR = 0.89 (0.80–1.01) and HR = 0.85 (0.70–1.03)), respectively.

We hypothesized that pneumococcal vaccination or high levels of anti-pneumococcal antibodies are associated with high levels of anti-oxLDL antibodies independently of other factors. To our knowledge, no study to date has correlated the response to pneumococcal vaccine, as measured by anti-pneumococcal antibodies, with titers of anti-oxLDL antibodies. The objective of this study was to assess the association between pneumococcal vaccination status, anti-pneumococcal antibody levels and oxLDL antibody level in a population with no history of cardiovascular disease.

Section snippets

Design

Participants were selected randomly from the Hunter Community Study, a population-based cohort of community dwelling Australians between the ages of 55 and 85, drawn from the federal electoral roll [14]. They were excluded from the current study if they reported any past history of cerebrovascular disease or ischemic heart disease.

Methods

A random sample of those with (n = 60) and without (n = 60) previous self-reported pneumococcal vaccination (23-valent vaccine, Pneumovax, Merck) were chosen and the report of vaccination was cross checked using Medicare Pharmaceutical Benefits Scheme (PBS) data. Serum stored at baseline was analyzed for total anti-pneumococcal antibody IgG titer and anti-oxLDL antibody titer by ELISA assay. Pneumococcal antibodies were assayed using the 23-valent vaccine as the capture antigen at the IMVS clinical

Analysis

The outcome of interest was anti-oxLDL antibody titers; given the non-normal distribution of this variable, it was dichotomized. Continuous variables were assessed using a Mann–Whitney test or Fisher's exact test and dichotomous variables were assessed using a Chi2 test. Univariate logistic regression was performed initially; variables with p < 0.2 were considered for inclusion in the multivariate logistic regression. Data analysis was performed using Stata Statistical Software: Release 10

Results

The histogram of the anti-ox-LDL titers in all 116 participants shows a roughly bimodal distribution with a nadir at 35,000 units. This was taken as a cut point for analysis, creating low and high anti-oxLDL titer groups (Fig. 1). Fig. 2 shows the histogram distribution of IgG antibodies against pneumococcus. The spike at the upper end of the spectrum (at 270) reflects the limit of detection for the assay; readings above this level were assigned a value of 271 for the analysis.

No significant

Discussion

This preliminary study provides further evidence in support of the protective chain between pneumococcal vaccine and a potential cardioprotective effect, and is the first study to our knowledge that measures and correlates anti-pneumococcal antibodies and anti-oxLDL antibodies in the same participants.

The lack of association between self-reported pneumococcal vaccination and anti-oxLDL antibodies suggests some degree of error in reporting. However, this cannot entirely explain the lack of

Acknowledgements

This study was funded by a cardiovascular lipid research grant from Pfizer Australia, and the Australian Research Council.

References (15)

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