Dr Linterman and her lab team compared over 50 different immune variables in individuals before and after vaccination, including the level of neutralizing antibodies raised to the protein the ‘flu virus uses to enter cells (haemagglutinin), cell signaling molecules and B and T cell responses.
They could track the immune cells that responded to the vaccination to be certain that the changes they were seeing were a result of the vaccine.
The number of circulating T follicular helper cells (cTfh) that specifically recognise the influenza protein haemagglutinin were the best indicator for a strong immune response and that these cells differentiate from pre-existing memory cells, but that in older people this differentiation process is reduced.
They investigated the transcriptome to detect differences in the genes expressed in the vaccine-specific cTfh cells from younger and older individuals.
They found that cells from older individuals failed to acquire the full gene signature seen in Tfh cells from younger people. Moreover, they detected the activation of pro-inflammatory signaling pathways in cTfh cells from older people in response to vaccination, which negatively impacts an optimal vaccine response.
Dr Linterman said: “Understanding the molecular events behind our body’s response to vaccination shows us what is happening when the immune response isn’t as strong as it could be.
Our research provides a proof of concept that increased inflammation is a feature of the vaccination response in older people and that this limits the formation of T follicular helper cells, which are essential for good antibody production..
This suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunization of older people.”