Long-term protection after primary yellow fever vaccination in elderly persons (60 years or older at the time of primary vaccination)

The objective of this project is to assess the persistence of protective yellow
fever virus neutralizing antibodies (YFVNA) titers, ten years after a primary
yellow fever vaccination in travelers of sixty years and older at the time of
vaccination.
In 2008-2009 we performed a controlled cohort clinical trial in 58 travellers
comparing antibody response and viremia after primary vaccination with live
attenuated 17D yellow fever vaccine (YF-17D) in elderly travelers (60-81 years
at vaccination, N = 28) and young volunteers (18-28 years at vaccination, N
=30).

The elderly persons had a delayed antibody response and higher viremia compared
to the control group. In all cases the World Health Organization (WHO) standard
of seroprotection (*80% virus neutralization at 1:10 serum dilution) was
reached after 30 days [1]. This result led us to the hypothesis that with older
age, a weaker initial 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, the vaccine-induced yellow fever.
In 2016, the WHO stipulated that the standard yellow fever vaccination induces
lifelong protection, and that a booster vaccination is no longer needed after
10 years. [2] Whether this also applies to elderly vaccinated persons has never
been investigated, and is a relevant question to be addressed in the light of
waning immunity with age, and an increasing elderly travel population.
Our hypothesis is that vaccine-induced lifelong immunity after one standard
YF-17D vaccination is not necessarily applicable to individuals of 60 years and
older.

The results of this research contribute significantly to the field of Travel
Medicine, especially for elderly travelers who have been vaccinated with YF-17D
at 60 years or older, and who are planning to visit a yellow fever endemic
country in the nearby future. In addition, the results will have important
implications for persons of 60 years and older who are living in yellow fever
endemic areas.

If this follow-up study shows that elderly persons do not confer long-term
protection (defined as 10 years) after standard YF-17D vaccination, measures
should be taken to protect them if they are at risk for new exposure to wild
type yellow fever virus.

This is a follow-up study of the initial study cohort of 2008-2009 [1]. All
participants from the original study population gave permission to be contacted
again in the future. These participants will be invited to provide a serum
sample for serological testing. Travel history, documented flavivirus
infections or vaccinations in the past ten years will be recorded. Participants
will be excluded if they have been revaccinated against yellow fever after the
initial trial. YFVNA will be determined by plaque reduction neutralization test
(PNRT). PRNT will be performed by the Laboratory of Virology of the Leiden
University Medical Center (LUMC).

Samples size calculation is not applicable as we will not be able to include
more participants than those who participated in the initial trial. We have
already contacted most participants and they are all willing to participate.

Negligible risk (only one venous puncture)