Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p=0.03) with higher YF-17D RNA copy numbers in the elderly participants. == Conclusions == We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. the elderly participants. == Conclusions == We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD. == Trial Registration == Trialregitser.nlNTR1040 == Introduction == The live attenuated 17D yellow fever vaccine is regarded as one of the safest and most effective vaccines[1]. However, in immunocompromized individuals yellow fever vaccination can cause fatal adverse events[2],[3]. A hampered immune response could allow the vaccine virus to replicate unrestrictedly, leading to vaccine-associated disease that resembles wild type yellow fever (yellow fever vaccine associated viscerotropic disease, YEL-AVD). YEL-AVD is fatal in 50% of cases[4]. In the last decade, a series of these serious and sometimes fatal adverse events following yellow fever vaccination has been reported[5][11]. The risk of YEL-AVD is increased for those with a history of thymectomy[12], male gender[13]and with increasing age. For vaccinees of 6069 years Tiglyl carnitine this risk is estimated to be 1100.000 doses and for vaccinees of 70 years it is 2.33.2100.000, which is approximately a 4 and 11 fold higher risk than the risk for young adults[13],[14]. The higher risk of YEL-AVD in elderly travelers has resulted in a more restrictive policy towards vaccinating travelers of 60 years and older, also advised by the World Health Organisation and Centers for Disease Control en Prevention[15][18]. In this group the risk of serious adverse events following vaccination is weighed against the risk of infection, using disease surveillance Tiglyl carnitine data of the WHO and reports of yellow fever outbreaks. The biological mechanism for the association between adverse events and older age has not yet been elucidated[4]. Both innate and adaptive immune responses wane with increasing age[19]. This may allow the attenuated vaccine virus more time to replicate and cause adverse events in elderly subjects. In this study we focused on humoral immunity, as this is considered to confer protective immunity against yellow fever. We tested the hypothesis that the adaptive immune response to yellow fever vaccine develops more slowly in elderly than in young subjects. == Methods == The protocol for this trial and supporting checklist are available as supporting information; seeChecklist S1andProtocol S1. == Ethics statement == The protocol and consent forms were approved by the Dutch Central Committee of Human Research (CCMO) and by the Medical Ethical Committee of the Leiden University Medical Center (LUMC) in the Netherlands. The trial was registered under NTR1040 and ISRCTN42180653, (http://irsctn.org). Written informed consent was obtained from each participant prior to inclusion. == Objectives == This study was conducted to determine whether the adaptive immune response to yellow fever vaccine is slower to develop in persons of 60 years or older compared with persons aged 18 to 40 years. Primary outcomes were the humoral response to yellow fever vaccination, measured by Plaque Reduction Neutralization Test (PRNT), and Yellow Fever 17D (YF-17D) viraemia FLJ30619 after vaccination, which was quantified by real time PCR (qRT-PCR). Secondary outcomes were adverse events. == Study design and Participants == In this prospective controlled cohort study, participants were recruited at the Travel Clinic of the Leiden University Medical Center (LUMC), and Municipal Health Centers of Leiden and The Hague, the Netherlands. Healthy volunteers aged between 18 and 40 years and eligible Tiglyl carnitine for inclusion into the control group were invited to participate. Participants in the control group were not necessarily planning.
