Associations between markers of cellular and humoral immunity to rubella virus following a third dose of measles-mumps-rubella vaccine

Introduction: Rubella virus (RV) was eliminated in the United States in 2004, although a small portion of the population fails to develop long-term immunity against RV even after two doses of the measles-mumps-rubella (MMR) vaccine. We hypothesized that inherent biological differences in cytokine and chemokine signaling likely govern an individual's response to a third dose of the vaccine. Methods: Healthy young women (n = 97) were selected as study participants if they had either low or high extremes of RV-specific antibody titer after two previous doses of MMR vaccine. We measured cytokine and chemokine secretion from RV-stimulated PBMCs before and 28 days after they received a third dose of MMR vaccine and assessed correlations with humoral immune response outcomes. Results: High and low antibody vaccine responders exhibited a strong pro-inflammatory cellular response, with an underlying Th1-associated signature (IL-2, IFN-γ, MIP-1β, IP-10) and suppressed production of most Th2-associated cytokines (IL-4, IL-10, IL-13). IL-10 and IL-4 exhibited significant negative associations with neutralizing antibody titers and memory B cell ELISpot responses among low vaccine responders. Conclusion: IL-4 and IL-10 signaling pathways may be potential targets for understanding and improving the immune response to rubella vaccination or for designing new vaccines that induce more durable immunity.