title: Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study.
abstract: BACKGROUND
  Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects.
  
  
  METHODS
  We vaccinated young volunteers (18-28 yrs, N = 30) and elderly travelers (60-81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination.
  
  
  RESULTS
  Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8-4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1-2.9, p = 0.02, using a mixed linear model. 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. 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.
  
  
  BACKGROUND
  Trialregitser.nl NTR1040.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. a.h.e.roukens@lumc.nl
authors.forename: Anna H
authors.initials: AH
authors.lastname: Roukens
authors.forename: Darius
authors.initials: D
authors.lastname: Soonawala
authors.forename: Simone A
authors.initials: SA
authors.lastname: Joosten
authors.forename: Adriëtte W
authors.initials: AW
authors.lastname: de Visser
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
authors.forename: Kees
authors.initials: K
authors.lastname: Dirksen
authors.forename: Marjolein
authors.initials: M
authors.lastname: de Gruijter
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bredenbeek
authors.forename: Leo G
authors.initials: LG
authors.lastname: Visser
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000737:chemistry; D015331:Cohort Studies; D006801:Humans; D009500:Neutralization Tests; D012306:Risk; D012307:Risk Factors; D013997:Time Factors; D014611:Vaccination; D014766:Viremia / Q000097:blood; D015004:Yellow Fever / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000009:adverse effects*; D015005:Yellow fever virus / Q000378:metabolism*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D022341:Yellow Fever Vaccine