How to boost immune response to vaccines in older people
Apply immune expertise and some genital wart cream!
March 27, 2020
Science Daily/Babraham Institute
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy aging for an aging population. Immunologists have identified a route for counteracting the age-related loss of two key immune cell types by using genital wart cream to boost immune response to vaccination in aged mice. After this validation in mice, the findings offer an attractive intervention to tailor the make-up of vaccines for older people.
Research just published by the Linterman lab shows that the immune system of older mice can be given a helping hand by applying immunology expertise and some genital wart treatment (don't try this at home just yet)!
Mice and humans show similar age-dependent changes in their immune system so this finding offers hope for easily increasing the robustness of vaccination response in the older population.
As we age, the function of our immune system declines, rendering us more susceptible to infections, and making us less able to generate protective immunity after vaccination. By understanding the cellular and molecular mechanisms that underpin this poor response in older individuals, researchers in the Linterman lab were able to repurpose an existing treatment for genital warts, and demonstrate that this was effective in overcoming the age-related effects on two of the many cell types making up our immune system. The research is published online in the journal eLife.
Dr Michelle Linterman, a group leader in the Institute's Immunology research programme, said: "The current coronavirus pandemic highlights that older members of our families and communities are more susceptible to the morbidity and mortality associated with infectious diseases. Therefore, it is imperative that we understand how the immune system in older people works, and to explore how we might be able to boost their immune responses to vaccines to ensure they work well in this vulnerable part of our society."
Vaccines work by generating antibodies that are able to block the ability of pathogens to infect us. Antibody secreting cells are produced in the germinal centre, immune reaction hubs that forms after infection or vaccination. With age, the magnitude and quality of the germinal centre reaction declines.
Immune cells called T follicular helper cells are essential to the germinal centre response. In this study the team used mice and humans to investigate why T follicular helper cell numbers decline with age, and if there is a way to boost them upon vaccination.
"The germinal centre response is a highly collaborative process that requires multiple cell types to interact at the right place and the right time. Therefore, it made sense to us that defects in one or more of these cell types could explain the poor germinal centre response observed in older individuals after vaccination," explains Dr Linterman.
The researchers found that older mice and humans form fewer T follicular helper cells after vaccination, which is linked with a poor germinal centre response and antibody response. By developing our understanding of the cellular and molecular events occurring in the germinal centre after vaccination, the researchers identified that T follicular helper cells in older mice and people received less stimulatory interactions from their immune system co-workers. By using a cream (imiquimod, currently used to treat genital warts in humans) on the site of immunisation to boost the number of stimulatory cells, they were able to restore the formation of T follicular helper cells in older mice and also rescue the age-dependent defects in another immune cell type (dendritic cells). Encouragingly, this demonstrates that the age-related defects in T follicular helper cell formation in ageing are not irreversible, and can be overcome therapeutically.
The full picture and evaluation of whether this approach will work as an intervention in humans requires more research into why the germinal centre response changes with age, and what can be done to overcome this. Once achieved, it could be that clinical trials are established to incorporate this knowledge into new vaccine formulations for older people.
https://www.sciencedaily.com/releases/2020/03/200327113752.htm
Biological clock influences immune response efficiency
September 24, 2019
Science Daily/McGill University
The biological clock influences immune response efficacy. Indeed, CD8 T cells, which are essential to fight infections and cancers, function very differently according to the time of day.
According to a recent study published in Proceedings of the National Academy of Sciences, the biological clock influences immune response efficacy. Indeed, CD8 T cells, which are essential to fight infections and cancers, function very differently according to the time of day. The study was carried out by a team of researchers led by Nicolas Cermakian, PhD, of the Douglas Research Centre, and Nathalie Labrecque, PhD, of the Maisonneuve-Rosemont Hospital Research Centre.
We know that circadian rhythms are generated by "clock genes," which influence most organs and cells -- including those of the immune system, whose function varies according to the time of day. Accordingly, circadian rhythms are found for various aspects of physiology, including sleep, nutrition, hormonal activity, and body temperature. These daily rhythms help the body adapt to cyclical changes in the environment, such as seasons and the day and night cycle.
In earlier research, the team had demonstrated that T cells react more or less strongly to a foreign body according to the time of day, but the role of the biological clock in this phenomenon remained unknown. "Using a mouse vaccine model, we observed that after vaccination, the strength of the CD8 T cell response varied according to the time of day. Conversely, in mice whose CD8 T cells were deficient for the clock gene, this circadian rhythm was abolished, and response to the vaccine was diminished in the daytime," explains Dr. Cermakian, who is also Professor at the McGill University Department of Psychiatry.
"Our study shows that T cells are more prone to be activated at certain times of the day. Identifying the mechanisms through which the biological clock modulates the T cell response will help us better understand the processes that regulate optimal T cell responses. This knowledge will contribute to improving vaccination strategies and cancer immune therapies," states Nathalie Labrecque, Professor at the Departments of Medicine and Microbiology, Infectious Diseases and Immunology at Université de Montréal.
https://www.sciencedaily.com/releases/2019/09/190924125015.htm