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A Randomized, Double-Blind, Controlled Trial of the 17D Yellow Fever Virus Vaccine Given in Combination with Immune Globulin or Placebo: Comparative Viremia and Immunogenicity

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  • Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia; Centers for Disease Control and Prevention, Fort Collins, Colorado; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas; Sanofi Pasteur, Swiftwater, Pennsylvania

We evaluated whether coadministration of the yellow fever (YF) virus vaccine with human immunoglobulin (Ig) that contained YF virus-neutralizing antibodies would reduce post-vaccination viremia without compromising immunogenicity and thus, potentially mitigate YF vaccine-associated adverse events. We randomized 80 participants to receive either YF vaccine and Ig or YF vaccine and saline placebo. Participants were followed for 91 days for safety and assessments of viremia and immunogenicity. There were no differences found between the two groups in the proportion of vaccinated participants who developed viremia, seroconversion, cluster of differentiation (CD)-8+ and CD4+ T-cell responses, and cytokine responses. These results argue against one putative explanation for the increased reporting of YF vaccine side effects in recent years (i.e., a change in travel clinic practice after 1996 when hepatitis A prophylaxis with vaccine replaced routine use of pre-travel Ig, thus potentially removing an incidental YF vaccine-attenuating effect of anti-YF virus antibodies present in Ig) (ClinicalTrials.gov identifier: NCT00254826).

Author Notes

* Address correspondence to Mark J. Mulligan, The Hope Clinic of the Emory Vaccine Center, 603 Church Street, Decatur, GA 30030. E-mail: mark.mulligan@emory.edu† These authors contributed equally.‡ Deceased.

Financial support: This work was supported by a grant from Sanofi Pasteur. This work was facilitated by the Center for AIDS Research (CFAR) at Emory University (P30 AI050409).

Disclosure: D.T. was employed by the study sponsor, Sanofi Pasteur, at the time that the study was conducted. Seema Garg moved to Sanofi Pasteur after the study was completed. These statements are made in the interest of full disclosure and not because the authors consider their employment to be a conflict of interest.

Authors' addresses: Srilatha Edupuganti and Mark J. Mulligan, The Hope Clinic of Emory Vaccine Center, Decatur, GA, E-mails: sedupug@emory.edu and mark.mulligan@emory.edu. Rachel B. Eidex, Centers for Disease Control and Prevention, Division of Global Migration and Quarantine, Pretoria, South Africa, E-mail: eidexr@sa.cdc.gov. Harry Keyserling, Emory Children's Center, Atlanta, GA, E-mail: hkeyser@emory.edu. Rama S. Akondy and Rafi Ahmed, Emory Vaccine Center, Atlanta, GA, E-mails: rakondy@emory.edu and rahmed@emory.edu. Robert Lanciotti, Centers for Disease Control and Prevention, Fort Collins, CO, E-mail: rsl2@cdc.gov. Walter Orenstein, Emory University School of Medicine, Atlanta, GA, E-mail: worenst@emory.edu. Carlos del Rio, Rollins School of Public Health, Emory University School of Medicine, Atlanta, GA, E-mail: cdelrio@emory.edu. Yi Pan, Tucker, GA, E-mail: jnu5@cdc.gov. Troy Querec and Martin Cetron, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: tquerec@cdc.gov and mzc4@cdc.gov. Alan Barrett, University of Texas Medical Branch, Sealy Center for Vaccine Development and Department of Pathology, Galveston, TX, E-mail: abarrett@utmb.edu. Dirk Teuwen, UCB Pharma, Chemin du Foriest, Braine, l'Alleud, Belgium, E-mail: dirk.teuwen@ucb.com.

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