Downloaded from http://journals.lww.com/pidj by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 07/03/2021 Copyright © 2021 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. The Pediatric Infectious Disease Journal • Volume XX, Number XX, XXX XXX www.pidj.com | 1 Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Quadrivalent Human Papillomavirus Vaccine in Boys and Girls 9–13 Years of Age in Malaysia A Phase IIIb, Randomized, Open-label Study Jamiyah Hassan, MMed,* Teck-Hock Toh, FRCPCH,† Selva Kumar Sivapunniam, MMed,‡ Ruziaton Hasim, MMed,§ Nor Faizah Ghazali, MFM,¶ Sofiah Sulaiman, MMed,* Mia Tuang Koh, FRCP,∥ Stephanie Meyer, PharmD,** Myew-Ling Toh, MD,** Celine Zocchetti,** Claire Vigne,†† and Cesar Mascareñas, MD‡‡ Background: Incorporating dengue vaccination within existing vaccina- tion programs could help improve dengue vaccine coverage. We assessed the immunogenicity and safety of a quadrivalent human papillomavi- rus (HPV) vaccine administered concomitantly or sequentially with a tetravalent dengue vaccine (CYD-TDV) in healthy children 9–13 years of age in Malaysia. Methods: In this phase IIIb, open-label, multicenter study (NCT02993757), participants were randomized 1:1 to receive 3 CYD-TDV doses 6 months apart and 2 doses of quadrivalent HPV vaccine concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Only baseline dengue-seropositive participants received the 3 doses. Antibody levels were measured at baseline and 28 days after each injection using an enzyme- linked immunosorbent assay for HPV-6, -9, -16 and -18, and the 50% plaque reduction neutralization test for the 4 dengue serotypes; immuno- genicity results are presented for baseline dengue-seropositive participants. Safety was assessed throughout the study for all participants. Results: At baseline, 197 of 528 (37.3%) randomized participants were dengue-seropositive [n = 109 (concomitant group) and n = 88 (sequential group)]. After the last HPV vaccine dose, antibody titers for HPV among baseline dengue-seropositive participants were similar between treatment groups, with between-group titer ratios close to 1 for HPV-6 and 0.8 for HPV-11, -16, and -18. After CYD-TDV dose 3, dengue antibody titers were similar between treatment groups for all serotypes [between-group ratios ranged from 0.783 (serotype 2) to 1.07 (serotype 4)]. No safety concerns were identified. Conclusions: The immunogenicity and safety profiles of CYD-TDV and quadrivalent HPV vaccines were unaffected when administered concomi- tantly or sequentially in dengue-seropositive children. Key Words: dengue vaccine, human papillomavirus vaccine, immuno- genicity, Malaysia, safety (Pediatr Infect Dis J 2021;XX:00–00) D engue is a mosquito-borne viral disease that is endemic in regions with tropical and sub-tropical climates.1,2 Dengue dis- ease can present as mild and self-limiting flu-like symptoms, but some individuals develop complications such as severe dengue or dengue shock syndrome (DSS) resulting in an estimated 500,000 hospitalizations and 22,000 deaths globally.3 Travel acquired dengue is playing an increasingly important role in dengue trans- mission with, dengue now the leading cause of febrile illness in returning travelers and the second highest cause of traveler hospi- talizations in Europe.4,5 ISSN: 0891-3668/21/XXXX-0000 DOI: 10.1097/INF.0000000000003164 Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Com- mons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC- ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Vaccine Reports Accepted for publication March