Assessing the influence of solar ultraviolet radiation exposure on the primary immune response to immunisation with a protein antigen in humans
Creators: name: Swaminathan, Ashwin
Publisher: name: The Australian National University
Year: 2013
Subjects: subject: Radiation immunology
subject: Ultraviolet radiation Physiological effect
subject: Solar radiation Physiological effect Research Australia Canberra (A.C.T.)
subject: Solar radiation Physiological effect Research Australia Townsville (QLD)
subject: Skin Effect of radiation on Australia
subject: Antigens

description: Ultraviolet radiation (UVR) is immunosuppressive, particularly to antigen-specific cell-mediated processes, acting via direct and indirect (e.g. vitamin D-mediated) pathways. This research aimed to examine the influence of acute and cumulative solar UVR exposure, at doses relevant to day-to-day activities, on the primary immune response to immunisation in humans. The Australian Ultraviolet Radiation and Immunity (AusUVI) Study was a prospective, longitudinal, twin-centre immunotoxicological study. Healthy adults were immunised subcutaneously with the T-cell dependent antigen, keyhole limpet haemocyanin (KLH). Acute personal UVR exposure was measured by electronic UVR dosimeter worn on the wrist for ten days centred on the day of immunisation; and by sun diary. Cumulative UVR exposure was quantified by microtopographic analysis of silicone impressions of sun exposed skin. Variables that might confound the association between UVR and vaccine immune response were measured, including serum vitamin D (25(OH)D) level. Participants attended for five study visits over a period of 31 days, with recruitment spread over one year. Immune function outcomes were: anti-KLH IgG1 antibody levels measured by enzyme linked immunoassay; delayed-type hypersensitivity (DTH) response to KLH antigen (reflecting T helper cell-1 (Th1) processes); and quantification of T-helper cell subsets by flow cytometry-based methods. A pilot study trialled many components of the AusUVI Study protocol and immune assays. The AusUVI Study was conducted in the Australian cities of Canberra (35o2'S) and Townsville (19o1'S) from July 2010 to August 2011. Two hundred and twenty two healthy participants were recruited (Canberra: 110; Townsville: 112). Participants' average age was 27.9 years (range: 18 - 40 years) and 63.5% were female. Participants with both parents of northern European ancestry (70.0%) predominated. 25(OH)D levels and personal UVR exposure varied by season and by site of enrolment. Townsville participants had higher 10-day clothing-adjusted UVR exposure compared with Canberra participants (2.5 vs.1.8 standard erythemal dose (SED); p=0.003). Higher cumulative UVR exposure was strongly associated with age, male sex, Townsville residence and northern European ancestry. In multiple linear regression models, anti-KLH IgG1 response at day 21 post-immunisation was associated with age (antibody titre reduced by 1.6% per year of age; p=0.001) and sex (14.6% higher titre in females compared with males (p=0.004)). No association between KLH IgG1 response and acute or cumulative UVR exposure, or serum 25(OH)D levels was demonstrated. Reduced DTH response to KLH recall challenge at day 21 post-immunisation was associated with higher acute UVR exposure on the day prior ('Day 5') to immunisation (p=0.015), and Days 5-8 and 5-9 (p=0.039 and p=0.025, respectively) that spanned the pre- and post-immunisation period. No association with cumulative UVR or serum 25(OH)D levels was demonstrated. Change in T-helper 17 (Th17) cell percentage between pre- and post-vaccination time points differed in direction when comparing the low and high UVR exposure groups (-0.39% vs. 0.31%; p=0.004). In conclusion, acute personal solar UVR exposure, at doses relevant to day-to-day activities, modulated the primary cell-mediated immune responses to KLH immunisation. Cumulative UVR exposure and serum 25(OH)D levels were not associated with immune function outcomes.