Brief reportPneumococcal vaccination may induce anti-oxidized low-density lipoprotein antibodies that have potentially protective effects against cardiovascular disease
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.
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Cited by (20)
Generation of cardio-protective antibodies after pneumococcal polysaccharide vaccine: Early results from a randomised controlled trial
2022, AtherosclerosisCitation Excerpt :Anti-OxLDL antibodies, such as those to PC that would be boosted by immunisation with PPV appear to reduce atherosclerosis via multiple different mechanisms including: blocking the uptake of OxLDL by macrophages thereby reducing the formation of foam cells, reducing cellular toxicity and apoptosis, and reducing both localised and systemic inflammation due to oxidised phospholipids [15–17]. PPV (Pneumovax, Merck Sharpe and Dohme) administration has been associated with the same anti-OxLDL antibodies in humans [18], but PCV (protein conjugate vaccine, Prevenar, Pfizer) does not seem to elicit the same degree of response [19]. Some international observational studies have provided evidence for an association between PPV and reduced risk of cardiovascular ischemic events [20,21] while other studies have not [22,23].
Pneumococcal polysaccharide vaccine is a cost saving strategy for prevention of acute coronary syndrome
2021, VaccineCitation Excerpt :It is believed that a phospholipid in the bacterial cell wall, phosphorylcholine, exhibits molecular mimicry with oxLDL [6–8]. Indeed, PPV administration has been observed to induce anti-oxLDL antibodies in humans [9]. Some observational studies have demonstrated an association between PPV and reduced risk of ischemic events in cardiovascular disease (CVD) [10,11], while other studies have not [12,13].
Pneumococcal polysaccharide vaccine associated with reduced lengths of stay for cardiovascular events hospital admissions: Experience from the Hunter Community Study
2018, VaccineCitation Excerpt :It is believed that a phospholipid in the bacterial cell wall, phosphorylcholine, exhibits molecular mimicry with oxLDL [5–7]. Indeed, PPV administration has been observed to induce anti-oxLDL antibodies in humans [8]. Some international observational studies have demonstrated an association between PPV and reduced risk of ischemic events in CVD [9,10], while other studies have not [11,12].