Stephen N Crooke1, Inna G Ovsyannikova1, Richard B Kennedy1, Nathaniel D Warner2, Gregory A Poland3. 1. Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA. 2. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA. 3. Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA. Electronic address: poland.gregory@mayo.edu.
Abstract
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.
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.
Authors: Inna G Ovsyannikova; Hannah M Salk; Beth R Larrabee; V Shane Pankratz; Gregory A Poland Journal: Immunogenetics Date: 2014-08-21 Impact factor: 2.846
Authors: Iana H Haralambieva; Inna G Ovsyannikova; Richard B Kennedy; Krista M Goergen; Diane E Grill; Min-Hsin Chen; Lijuan Hao; Joseph Icenogle; Gregory A Poland Journal: Vaccine Date: 2019-11-12 Impact factor: 3.641
Authors: Richard B Kennedy; Inna G Ovsyannikova; Iana H Haralambieva; Nathaniel D Lambert; V Shane Pankratz; Gregory A Poland Journal: Hum Genet Date: 2014-08-07 Impact factor: 4.132
Authors: Marguerite M Riggenbach; Iana H Haralambieva; Inna G Ovsyannikova; Daniel J Schaid; Gregory A Poland; Richard B Kennedy Journal: Clin Immunol Date: 2021-12-28 Impact factor: 3.969