title: Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination.
abstract: Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Kongsgaard
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Bassi
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: Department of Cancer and Inflammation, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Skjødt
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Thybo
authors.affiliation: Medical Office, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Gabriel
authors.affiliation: Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Morten Bagge
authors.initials: MB
authors.lastname: Hansen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan Pravsgaard
authors.identifier: http://orcid.org/0000-0002-4299-9479
authors.initials: JP
authors.lastname: Christensen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan Randrup
authors.identifier: http://orcid.org/0000-0002-2392-9803
authors.initials: AR
authors.lastname: Thomsen
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. SBuus@sund.ku.dk.
authors.forename: Soren
authors.initials: S
authors.lastname: Buus
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. AStryhn@sund.ku.dk.
authors.forename: Anette
authors.initials: A
authors.lastname: Stryhn
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003718:Denmark; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008875:Middle Aged; D062486:Public Health Surveillance; D014611:Vaccination; D015004:Yellow Fever / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D022341:Yellow Fever Vaccine