Genomic signature of early T-cell response is associated with lower antibody titer threshold for sterilizing immunity.

Authors:
Eugenia Z Ong
Eugenia Z Ong
8 College Road
Singapore
Limin Wijaya
Limin Wijaya
Singapore General Hospital
Singapore
Xin Mei Ong
Xin Mei Ong
Duke-NUS Graduate Medical School
Yin Bun Cheung
Yin Bun Cheung
London School of Hygiene and Tropical Medicine
United Kingdom

Antiviral Res 2019 Jun 30;166:35-41. Epub 2019 Mar 30.

Viral Research and Experimental Medicine Centre @ SingHealth-Duke NUS, Singapore; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2019.03.013DOI Listing
June 2019
3 Reads

Publication Analysis

Top Keywords

sterilizing immunity
20
t-cell response
8
mmr vaccination
8
serological response
8
early t-cell
8
herd immunity
8
pathogen transmission
8
immunity
7
response
5
sterilizing
5
response non-response
4
non-response measles
4
immunity observed
4
correlates serological
4
infection sterilizing
4
measles mumps
4
vaccination surrogates
4
surrogates infection
4
day post-vaccination
4
molecular correlates
4

Similar Publications