Measurement of yellow fever vaccine efficacy; is 10 years the right point in time for revaccination?

The yellow fever vaccine (17D strain) has been in use since 1937 when it was
used in a mass
vaccination campaign in Brazil [1]. In travel medicine, it is administered to
travelers visiting
endemic countries or countries where vaccine is required [2] namely South
American and
African countries.
According to international health regulations, vaccines need to be
re-administered every 10
years [3]. The regulation is conservative, since vaccine immunity appears to
last several
decades if not for life. Previous studies have already provided a base of this
evidence by
showing that neutralizing antibodies persist in vaccinated persons for many
more years [4, 5].
Neutralizing antibodies have long been thought to be the primary protection
against the
Yellow fever virus [6]. Recent findings have indicated that the innate as well
as the CD8 T
cell response might also be important aspects in the immunologic protection. It
has been
shown that highly polyfunctional memory CD8+ T cells are elicited and
maintained, for years
after vaccination [7]. Probably, the responses of these cells are also
important in the long-term
immunologic protection against yellow fever virus.
With this study we aim to add to the knowledge about the long term humoral and
cellular
immunity against yellow fever vaccination, in order to provide a broader
scientific basis on
which guidelines can be improved for vaccination campaigns in endemic areas as
well as for
travelers seeking preventive healthcare advice.
In the AMC, around 1300 travelers receive a yellow fever vaccine annually. In
around 1 in
every 18 yellow fever vaccine recipients, the yellow fever vaccine is a booster
for a
previously administered vaccine.
In order to assess the duration of the immunologic response, we will measure
neutralizing
antibodies as well as T cell memory in travelers who attend our pre travel
clinic more than 10
years after a primary yellow fever vaccination.
Hypothesis: The duration of yellow fever vaccination protection lasts for over
10 years after
vaccination.

Reference list
1. Smith HH, Penna HA, Paoliello A. Yellow Fever vaccination with cultured
virus (17D)
without immune serum. Am J Publ Hlth 18:437, 1938.
2. Manso C, de S. Mass vaccination against yellow fever in Brazil 1937-54. In:
Smithburn
KC, et al, eds. Yellow Fever Vaccination. Geneva: WHO, 123-140, 1956.
3. WHO. Revision of the International Health Regulations. 58th World Health
Assembly.
WHA 58.3, 2005.
4. Poland JD, Persistance of neutralizing antibody 30-35 years after
immunization with 17D
yellow fever vaccine. Bull World Health Organ 59: 895-900, 1981.
5. Bodilis CG, Benebdelmoumen G, Gergely A, et al. [Long term persistence of
yellow fever
neutralising antibodies in elderly persons]. Bull Soc Pathol Exot 104:260-265,
2011.
6. Mason RA, Tauraso NM, Spretzel RO, et al. Yellow fever vaccine: direct
challenge of
monkeys given graded doses of 17D vaccine. Appl Microbiol 25:539, 1973.
7. Akondy RS, Monson ND, Miller JD, et al. The Yellow Fever virus vaccine
induces a broad
and polyfunctional human memory CD8+ T cell response. J Immunol., 183:
7919-7930, 2009.

Objectives:
1) By measuring neutralising antibodies as well as immune memory in travelers
vaccinated
previously (> 10 years ago) with yellow fever vaccine, an assessment of the
duration of
vaccine induced immunity can be made.
2) To provide the basis for considering a longer time period before
revaccination is
considered necessary with the current vaccine.

Trans sectional study including all travelers at the pre-travel clinic who have
been administered a
yellow fever vaccination > 10 years ago. All volunteers shall be asked to give
their informed
consent. Blood samples shall be drawn before new vaccinations are administered,
to
measure neutralizing antibodies and to measure T cell memory.
Of the group with no neutralizing antibodies, all volunteers shall be assessed
for the presence
of T cell memory. In the group with neutralizing antibodies, a random sample
(~32/105, 31%)
shall be analysed for the presence of T cell memory.

n.a.