Top Jabs - Improving vaccination responses in older adults

Older adults are more likely to get infections than young people, which is why the NHS vaccinates against the ?flu and pneumonia because of immune system ageing. Unfortunately, as people age, their body?s immune system works less well, meaning that responses to vaccination are less able to protect against illness. It is important to better understand why older people have poorer vaccine responses and to improve these. We plan to research this in older animals and humans. We will look at the processes involved in making high quality antibodies in mice, and test three ways of improving the vaccination response in mice and humans ? adding to vaccine components; improving people?s sensitivity to insulin; or simply changing the time of day when vaccines are given.

Older adults are more susceptible to bacterial and viral infections than young people and the national vaccination programmes against influenza and Streptococcus pneumonia are the primary preventive measure aimed at reducing incidence of these infections. However, the decline in immune function in old age reduces the ability of older individuals to mount successful vaccination responses, with less than half of over 65 year olds producing a protective response to influenza. With age both the quantity and quality of antibody produced is reduced, which will reduce the efficacy of vaccination in older adults. Many older adults are therefore not benefitting from the protection provided by vaccination. There is an urgent need to understand why the vaccination response is compromised in old age and to develop interventions to improve vaccination responses in elders.
We plan to address several aspects of the immune response to vaccination in older animals and humans to determine why there is a failure to develop good humoral immune responses in older adults. T cell memory and B cell differentiation are directed by adult lymphoid tissue inducer (LTi) cells. We will test if and how their reduced function impacts on reduced antibody responses in old age. In addition, immune complexes have been used as adjuvants in old mice, and we will study how antigen-masking changes selection and affinity maturation of B lymphocytes in lymphoid tissues in older animals. Crucially, we will test whether antigen-masking can be used as an efficient and novel vaccine adjuvant in older animals.
Age related hormonal and metabolic changes also contribute to reduced immune responses. The study will test whether insulin sensitivity is related to vaccination responses, and will test in a small pilot study in animals whether a pharmacological intervention (metformin treatment) can improve vaccine response. Finally, a simple behavioural intervention will be used to modulate efficiency of vaccination responses: Our preliminary data show that diurnal variations in older adults lead to changes in the quality of humoral vaccine responses. We will repeat this in a larger randomised trial and test whether diurnal changes in responsiveness are due to variations in stress hormones or cytokines. If proved effective, this observation will lead to a simple intervention by manipulating the timing of immunization to improve the response to vaccination in older adults.