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Improving vaccines for the elderly by blocking inflammation

Taking an anti-inflammatory pill could help make vaccines more effective for elderly people, a new UCL study has found.

The study has shown that an excessive skin inflammation reaction in older people can obstruct the immune system. Researchers have now identified how to block that inflammation short term.

Professor Arne Akbar, who is senior author said: “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.”

To investigate immune responses, the researchers injected 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.

By analysing skin biopsies post-injection, the researchers found that the excessive inflammation was associated with activation of the p38 MAP kinase pathway. To test whether this enzyme was to blame, they conducted a follow-up test with 18 of the over-65 participants, who took Losmapimod, a drug that inhibits the enzyme in order to reduce acute inflammation responses.

Losmapimod treatment successfully increased the immune responses to the VZV antigen.

The researchers found that the older subjects exhibited weaker immune responses, as there was less T cell activation, and less reddening and swelling of the skin. The reduced response was not due to a lack of resident memory T cells present in the skin.

Dr Milica Vukmanovic-Stejic, the study’s first author said: “A short-term blockade of the inflammation response opened up a window of opportunity for the immune system to respond effectively.”

The researchers are currently planning a follow-up study which will test whether a flu vaccine is more effective for the elderly when combined with brief use of Losmapimod.

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