title: Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity.
abstract: A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.
authors.affiliation: Australian Army Malaria Institute, Queensland, Australia.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nasveld
authors.forename: Joanne
authors.initials: J
authors.lastname: Marjason
authors.forename: Sonya
authors.initials: S
authors.lastname: Bennett
authors.forename: John
authors.initials: J
authors.lastname: Aaskov
authors.forename: Suzanne
authors.initials: S
authors.lastname: Elliott
authors.forename: Karen
authors.initials: K
authors.lastname: McCarthy
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kanesa-Thasan
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Feroldi
authors.forename: Mark
authors.initials: M
authors.lastname: Reid
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D005260:Female; D006801:Humans; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010919:Placebos / Q000008:administration & dosage; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D010948:Viral Plaque Assay; D015004:Yellow Fever / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; D010919:Placebos; D014613:Vaccines, Attenuated; D017778:Vaccines, Combined; D022341:Yellow Fever Vaccine