Characterization of humoral and cellular immunity to rubella vaccine in four distinct cohorts

Abstract

Although vaccination campaigns have significantly reduced the global burden of rubella disease, there are still regional outbreaks and cases of congenital rubella syndrome. Rubella vaccination elicits a strong humoral as well as cellular response. The relationship between these two measures in response to rubella vaccine is poorly understood. We have previously reported no correlation between rubella-virus-specific cytokine secretion and IgG antibody levels after rubella vaccination. In the current study, we extend our previous work to report correlations between secreted cytokines and functional neutralizing antibodies after rubella vaccination in four distinct cohorts. There was evidence of significant differences (p < 0.05) in rubella-virus-specific humoral and cellular responses between cohorts. When investigating relationships between rubella-vaccine-specific humoral and cellular immunity, we observed a significant correlation between neutralizing antibodies and IFN-γ (r(s) = 0.21, p = 0.0004). We also observed correlations in subjects with extreme humoral immune phenotypes and IFN-γ levels in two of the four cohorts (r(s) = 0.32, p = 0.01; r(s) = 0.36, p = 0.01, respectively). These findings indicate that there is a high level of heterogeneity in rubella-specific immune responses between study populations. We believe that the novel correlation discovered between IFN-γ and neutralizing antibody titers will give future insight into the functional mechanisms of immunity induced by rubella virus and other live viral vaccines.

Figure 1. Distribution of Humoral and Cellular Immune Responses across Cohorts

Box plots comparing secreted cytokine levels and NT₅₀ across cohorts. Rubella-specific IL-6 (Rochester 1 n = 297, Rochester 2 n = 380, Rochester 3 n = 311, San Diego n = 946) and IFN-γ (Rochester 1, n = 297, Rochester 2, n = 380, Rochester 3 n = 292, San Diego n = 925) levels were measured by ELISA and reported as the difference between rubella virus-stimulated and unstimulated values. NT₅₀ levels (Rochester 1, n = 318; Rochester 2, n = 373; Rochester 3, n = 338; San Diego, n = 985) were calculated using interpolated data from a high-throughput soluble immunochemical assay. There were significant differences in immune measures across cohorts. However, Rochester 2 and Rochester 3 displayed strikingly similar median values of NT₅₀ and IL-6 (ns = not significant; * = p ≤ 0.05; *** = p ≤ 0.001; **** = p ≤ 0.0001).