title: Atypical antibody responses in dengue vaccine recipients.
abstract: Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.
authors.affiliation: Walter Reed Army Institute of Research, Washington, District of Columbia, USA. niranjan.kanesa-thasan@det.amedd.army.mil
authors.forename: N
authors.initials: N
authors.lastname: Kanesa-Thasan
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.forename: G V
authors.initials: GV
authors.lastname: Ludwig
authors.forename: C
authors.initials: C
authors.lastname: Rossi
authors.forename: J R
authors.initials: JR
authors.lastname: Putnak
authors.forename: J A
authors.initials: JA
authors.lastname: Mangiafico
authors.forename: B L
authors.initials: BL
authors.lastname: Innis
authors.forename: R
authors.initials: R
authors.lastname: Edelman
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D017321:Clinical Trials, Phase I as Topic; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D016032:Randomized Controlled Trials as Topic; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000009:adverse effects; D014765:Viral Vaccines / Q000009:adverse effects; D014766:Viremia
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines