Through identifying the way skin reacts to pathogens in older patients, a team of researchers from University College London (UCL) have found that blocking inflammation may help improve vaccine efficacy.
vaccination
“We know that the immune system declines with age, and people can be affected by pathogens they were once immune to. We found that when it comes to cutaneous immunity — specific to skin — the immune system was being obstructed by skin cells that were too prone to producing inflammation responses. We’ve now identified a way to block that inflammation in the short term,” explained the study’s senior author, Professor Arne Akbar (UCL Infection & Immunity).
The study, which was published in The Journal of Allergy and Clinical Immunology, investigated immune responses by injecting an antigen into the skin of 172 participants. The specific pathogen used in this study was varicella zoster virus (VZV), which causes chicken pox. Once a person has contracted VZV they become immune and so shouldn’t catch it again but as they age, it is possible to re-activate causing shingles. This re-activation occurs if T-cell immune responses are not strong enough.
Of the participants involved in the study, the older ones were found to exhibit a weaker immune response as a result of less T cell activation. To compare the inflammation response found when the antigen was injected, the team also injected a benign saline solution in the other arm of the patients. On doing this, the researchers realised that even a saline solution brought about an inflammation response in the older patients. In fact, the participants who had the strongest inflammation response to the saline solution were found to have the weakest immune responses to VZV, indicating that excessive inflammation was inhibiting VZV-specific immunity.
“Normally inflammation is a healthy part of the body’s immune response, so we were surprised to find that in this case, too much inflammation was getting in the way of the rest of the body’s defences,” added Akbar.
Skin biopsies of the patients were taken post-injection and analysed to try to discern the cause of the excessive inflammation reaction. It was found that activation of the p38 MAP kinase pathway was associated with the inflammation, as such the team looked at whether Losmapimod — a drug designed to inhibit the enzyme — would help reduce acute inflammatory responses.
When taking Losmapimod for four days prior to injection with the VZV antigen participants exhibited increased immune responses.
“A short-term blockade of the inflammation response opened up a window of opportunity for the immune system to respond effectively,” explained the study’s first author, Dr Milica Vukmanovic-Stejic (UCL Infection & Immunity).
A follow up study is being planned by the researchers to investigate if administration of Losmapimod for a few days prior to vaccination may improve the efficacy of the flu vaccine in elderly patients.
“Vaccine efficacy is known to decline in old age, so we’re hopeful that this novel application of the drug could help make vaccines more effective in older people,” stated co-author Dr Veronique Birault (Francis Crick Institute).
Dr Jonathan Pearce, head of infections and immunity at the Medical Research Council (MRC), said: “This interesting study shows how our immune system changes as we age, with increased inflammatory responses potentially hindering our ability to raise a protective immune response to pathogens. This insight may help us improve vaccine responses in the elderly — a group at particular risk of diseases including influenza — by pre-treatment with anti-inflammatory agents.”