Ayling, Kieran
(2017)
Psycho-behavioural influences on vaccine success: towards a brief, non-pharmacological primary care intervention.
PhD thesis, University of Nottingham.
Abstract
Vaccines against infectious diseases are less effective in older adults than in younger adults. This is of significant clinical importance as older adults are also the most vulnerable to contracting, and suffering the most severe consequences of, infectious diseases. Prior research demonstrates that behavioural and psychological factors can modulate the immune system and, in turn, influence how well vaccines work. However, there is a relative paucity of work focusing on older adults. Further, studies have tended to consider only one behavioural or psychological factor at a time - meaning it is unclear which factor, or combination of factors, should be the target of interventions to enhance vaccine effectiveness. This thesis presents three distinct, yet inter-related, pieces of original research which sought to further our understanding of the behavioural and psychological influences on vaccinations and inform the future development of interventions to enhance vaccine effectiveness.
First, current approaches to measuring the immune response to vaccination (e.g., ELISAs) are limited in that they require large volumes of sera, antigen, and other consumables. This makes them expensive and time consuming, which limits their utility for larger studies. Thus, the first phase of the research involved establishing a novel high-throughput multiplex antigen microarray assay for quantifying influenza-specific IgG levels in sera. This involved adapting an existing microarray assay and validating it in a series of laboratory experiments. The microarray assay demonstrated acceptable intra- and inter-assay reliability and correlated well with ELISA (H1N1: rho=.534, p<.01; H3N2: rho=.802, p<.00001; B: rho=.454, p<.01). Crucially, the protocols developed could be adapted to suit a variety of research purposes in the future.
Second, a prospective longitudinal observational cohort study was conducted to investigate the influence of modifiable psychological and behavioural factors on short and long-term antibody responses to influenza vaccination in older adults (n=138). Diary methods, pedometers, and anthropometric measurements were used to assess nutrition, sleep, physical activity, affect and perceived stress repeatedly over the 2 weeks prior to, and 4 weeks following influenza vaccination. Greater positive affect across the measurement period was found in multivariate regression models to be a significant independent predictor of both short- (β=.189, p=.036) and long-term H1N1 antibody responses following vaccination (β=.296, p=.003): with greater positive affect predicting a more robust antibody response. However, positive affect on the day of vaccination was found be even more salient, explaining greater variance than positive affect over the longer period (H1N1 short term model: R2=.077 vs .058; long term model: R2=.136 vs .125). Greater variability in perceived stress over the measurement period predicted poorer long-term antibody responses to both H1N1 (β=-.268, p<.05) and B strains (β=-.255, p<.05), even after taking overall stress exposure into account.
Third, in view of the observed relationship between positive affect and immune responses to vaccination, and in particular the role of positive affect on the day of vaccination, a systematic scoping review was conducted to examine the effects of brief positive mood interventions on immunity. A moderate-sized (31 studies, 38 interventions), but relatively low quality, literature was identified. Few studies included older adults and none examined the effects on in-vivo immune challenges such as vaccination. While there was considerable heterogeneity in the form of interventions that elicited mood improvements, the clear majority of studies reported enhanced immunological outcomes (87.1%). However, many interventions were unsuitable in their current form for implementation within the current already resource-stretched UK health system.
Together, the work presented in this thesis points to the potential utility of brief, positive affect enhancing interventions as a way of enhancing immune responses to vaccination in older adults. Further methodologically rigorous research is needed to systematically develop and evaluate positive affect interventions that are both acceptable for older adults and feasible for implementation in the NHS.
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