title: Immunologic interference from sequential administration of live attenuated alphavirus vaccines.
abstract: Two different human vaccine trials examined interference arising from sequential administration of vaccines against heterologous alphaviruses. The first trial indicated that persons previously vaccinated against Venezuelan equine encephalitis virus (VEEV) exhibited poor neutralizing antibody responses to a live attenuated chikungunya virus (CHIKV) vaccine (46% response rate). The second trial prospectively examined neutralizing antibody responses to live attenuated VEEV vaccine in persons previously inoculated with either CHIKV vaccine or placebo. Following seroconversion to CHIKV, CHIKV vaccine recipients' geometric mean titers (GMTs) to VEEV by 80% plaque-reduction neutralization titration never exceeded 10, compared with a peak GMT of 95 after VEEV vaccination for alphavirus-naive volunteers who initially received placebo (P < .003). ELISA antibody responses demonstrated cross-reactive IgG to VEEV after primary CHIKV immunization and then an anamnestic response upon subsequent VEEV vaccination. These data indicate that preexisting alphavirus immunity in humans interferes with subsequent neutralizing antibody response to a live attenuated, heterologous vaccine.
authors.affiliation: Division of Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: McClain
authors.forename: P R
authors.initials: PR
authors.lastname: Pittman
authors.forename: H H
authors.initials: HH
authors.lastname: Ramsburg
authors.forename: G O
authors.initials: GO
authors.lastname: Nelson
authors.forename: C A
authors.initials: CA
authors.lastname: Rossi
authors.forename: J A
authors.initials: JA
authors.lastname: Mangiafico
authors.forename: A L
authors.initials: AL
authors.lastname: Schmaljohn
authors.forename: F J
authors.initials: FJ
authors.lastname: Malinoski
mesh_terms: D000293:Adolescent; D000328:Adult; D018354:Alphavirus Infections / Q000517:prevention & control*; D000914:Antibodies, Viral / Q000097:blood*; D002646:Chikungunya virus / Q000276:immunology*; D003429:Cross Reactions; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014762:Viral Interference / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines