title: Low antibody titers 5 years after vaccination with the CYD-TDV dengue vaccine in both pre-immune and naïve vaccinees.
abstract: Globally, dengue virus (DENV) is one of the most widespread vector-borne viruses. Dengue disease affects populations in endemic areas and, increasingly, tourists who travel to these countries, but there is currently no approved vaccine for dengue. A phase 3 efficacy trial with Sanofi-Pasteur's recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) conducted in South East Asia showed an overall efficacy of 56% against virologically confirmed dengue infections of any severity and any of the 4 serotypes, but the long-term protection of the vaccine has yet to be demonstrated. To address longevity of antibody titers and B cell memory, we recalled study participants from an earlier CYD immunogenicity study (Phase 2) conducted in Singapore that enrolled healthy volunteers in the year 2009. Depending on the age group, 57-84% of the participants initially generated a neutralizing antibody titer ≥ 10 to all 4 DENV serotypes 28 d after the third and final dose. We observed very low antibody titers in blood samples collected from 23 vaccinees 5 y after the first dose, particularly titers of antibodies binding to virus particles compared with those binding to recombinant E protein. The in vivo efficacy of plasma antibodies against DENV-2 challenge was also tested in a mouse model, which found that only 2 out of 23 samples were able to reduce viremia. Although the sample size is too small for general conclusions, dengue immune memory after vaccination with CYD-TDV appears relatively low.
authors.affiliation: a Singapore Immunology Network, Agency for Science, Technology (A*STAR) , Singapore , Singapore.
authors.forename: Sumathy
authors.initials: S
authors.lastname: Velumani
authors.affiliation: a Singapore Immunology Network, Agency for Science, Technology (A*STAR) , Singapore , Singapore.
authors.forename: Ying Xiu
authors.initials: YX
authors.lastname: Toh
authors.affiliation: b Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore , Singapore.
authors.forename: Shobana
authors.initials: S
authors.lastname: Balasingam
authors.affiliation: c Division of Infectious Diseases, University Medicine Cluster, National University Hospital , Singapore , Singapore.|d Department of Medicine , Yong Loo Lin School of Medicine, National University of Singapore , Singapore.
authors.forename: Sophia
authors.initials: S
authors.lastname: Archuleta
authors.affiliation: e Communicable Disease Center, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital , Singapore , Singapore.|f Yong Loo Lin School of Medicine, National University of Singapore , Singapore , Singapore.
authors.forename: Yee Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: e Communicable Disease Center, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital , Singapore , Singapore.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Gan
authors.affiliation: e Communicable Disease Center, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital , Singapore , Singapore.
authors.forename: Tun Linn
authors.initials: TL
authors.lastname: Thein
authors.affiliation: b Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore , Singapore.
authors.forename: Annelies
authors.initials: A
authors.lastname: Wilder-Smith
authors.affiliation: a Singapore Immunology Network, Agency for Science, Technology (A*STAR) , Singapore , Singapore.|b Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore , Singapore.
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D001208:Asia; D001402:B-Lymphocytes / Q000276:immunology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008875:Middle Aged; D012846:Singapore; D013997:Time Factors; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C000603176:CYD-TDV vaccine; D053059:Dengue Vaccines
keywords: antibodies; dengue; immune memory; long-term; memory B cells; vaccine