BCG vaccination is associated with longitudinal changes in systemic eicosanoid levels in elderly individuals: A secondary outcome analysis

Abstract

We investigated how BCG vaccination affects the levels of certain eicosanoids, namely Leukotriene B4, 15-epimer of LXA4, prostaglandin F2, Lipoxin A4, Prostaglandin E2 and Resolvin D1 in the plasma of healthy elderly individuals (aged 60-80) before vaccination, one month post-vaccination (M1), and six months post-vaccination (M6). This study is part of the clinical trial "BCG Vaccine Study: Reducing COVID-19 Impact on the Elderly in Indian Hotspots," registered in the clinical trial registry (NCT04475302). While some primary outcomes have been previously reported, this analysis delves into the immunological outcomes. Our findings indicate that BCG vaccination leads to reduced plasma levels of 15-epi-LXA4, LXA4, PGE2, and Resolvin D1 at both M1 and M6. In contrast, there is a notable increase in circulating levels of LTB4 at these time points following BCG vaccination. This underscores the immunomodulatory effects of BCG vaccination and hints at its potential to modulate immune responses by dampening inflammatory reactions.

Keywords: BCG; Eicosanoids; Inflammation; Leukotrienes; Lipoxins; Prostaglandins; Vaccines.

Fig. 1

BCG vaccination leads to decreased levels of eicosanoids compared to baseline. The circulating levels of eicosanoids in BCG pre-vaccinated [M0] (n = 44), month 1 post vaccinated [M1] and month 6 post vaccinated [M6] (n = 44) individuals are shown. The data are depicted through line diagrams, with each line representing an individual participant. To analyze M0, M1, and M6, p-values were computed using Wilcoxon matched-pair tests, with Holm's correction applied for multiple comparisons.

Fig. 2

Eicosanoid pathways are engaged in BCG vaccinated elderly individuals during baseline and post-vaccination. Canonical correlation analysis (CCA) was utilized to evaluate whether a combination of eicosanoids can differentiate between baseline (M0) and Month 1 (M1) compared to Month six (M6), as well as unvaccinated control (UVC). The data are presented in dot plots, where each dot symbolizes an individual participant.

Fig. 3

Relationship between eicosanoids. Multiparametric matrix correlation plot of eicosanoids in all individuals at baseline (M0), Month six (M1) and Month six (M6) post BCG vaccination. Spearman's correlation coefficients are displayed with differing color intensities, while P values and Spearman r values are arranged using hierarchical clustering. In the correlation plot, box sizes reflect correlation values ranging from −1 to +1; larger boxes denote stronger correlations. Blue color signifies positive correlations, whereas red color indicates negative correlations. p-value is statistically significant * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Relationship between eicosanoids and inflammatory cytokines. Multiparametric matrix correlation plot of eicosanoids and inflammatory cytokines in all individuals of baseline (M0), Month six (M1) and Month six (M6) post BCG vaccination. Spearman's correlation coefficients are depicted using varying color intensities. P values and Spearman r values are organized through hierarchical clustering. Within the correlation plot, the size of each box corresponds to the correlation value, ranging from −1 to +1; larger boxes indicate stronger correlations. Blue color signifies positive correlations, while red color indicates negative correlations. Significant p-values are denoted.* represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)