Genomic signature of early T-cell response is associated with lower antibody titer threshold for sterilizing immunity
Ong, Eugenia Z.; Gan, Esther S.; de Alwis, Ruklanthi; Wijaya, Limin; Ong, Xin Mei; Zhang, Menglan; Wong, Abigail WL; Cheung, Yin Bun; Zellweger, Raphaël M.; Ooi, Eng Eong; Low, Jenny G. (2019-06)
Ong, Eugenia Z.
Gan, Esther S.
de Alwis, Ruklanthi
Wijaya, Limin
Ong, Xin Mei
Zhang, Menglan
Wong, Abigail WL
Cheung, Yin Bun
Zellweger, Raphaël M.
Ooi, Eng Eong
Low, Jenny G.
06 / 2019
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202012148828
https://urn.fi/URN:NBN:fi:tuni-202012148828
Kuvaus
Peer reviewed
Tiivistelmä
Vaccination is an effective approach to reduce disease burden. High vaccination coverage blocks pathogen transmission to ensure herd immunity. However, the concept of herd immunity assumes that vaccinated individuals cannot be infected and mediate silent pathogen transmission. While the correlates of vaccine-mediated protection against disease have been examined, the correlates of sterilizing immunity that prevents infection have not been systematically defined. Here, we used full genome expression profiling to explore the molecular correlates of serological response and non-response to measles, mumps and rubella (MMR) vaccination as surrogates of infection and sterilizing immunity, respectively. We observed that the antibody titers needed to sterilize infection with the vaccine strains were higher than current WHO disease protection thresholds. In subjects with baseline antibodies below such sterilizing immunity thresholds, serological non-response to MMR vaccination was associated with gene expression profile indicative of early T-cell activation and signalling. Specifically, genes that regulate T-cell function and response were induced at day 1 post-vaccination in non-responders but not in responders. These findings suggest that rapid T-cell response prevented MMR vaccine infection to limit antigenic presentation and hence serological response. Collectively, our findings suggest an important role for T-cells in engendering sterilizing immunity.
Kokoelmat
- TUNICRIS-julkaisut [16929]