Blocking Inflammation Could Make Vaccines More Effective In the Elderly
“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.
To investigate immune responses, the researchers injected an antigen – a derivative of a pathogen that creates an immune response without inducing illness – into the skin of 175 participants (78 were over 65 years old and the rest were under 40). The pathogen was the varicella zoster virus (VZV), which causes chicken pox.
After a person contracts chicken pox, they become immune to VZV, but it can re-activate in old age and cause shingles if T cell immune responses aren’t strong enough. All study participants had previously had chicken pox, meaning they should be immune.
In the course of the study, older participants exhibited 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. This was met with the scientists realising 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.
On performing skin biopsies on the participants, the team 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).
“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 of the Francis Crick Institute.
Dr Jonathan Pearce, head of infections and immunity at the Medical Research Council 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.”
