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

Abstract

Background: Incorporating dengue vaccination within existing vaccination programs could help improve dengue vaccine coverage. We assessed the immunogenicity and safety of a quadrivalent human papillomavirus (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; immunogenicity 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 concomitantly or sequentially in dengue-seropositive children.

Conflict of interest statement

J.H., N.F.G., R.H. and S.S. received a grant from Sanofi Pasteur to conduct this study. J.H. received personal fees from Merck Sharp & Dohme, Johnson & Johnson, DKSH Malaysia, Nestle Malaysia, Ferring Pharmaceuticals, Sanofi Malaysia, Zuellig Pharma Malaysia, Abex Medical Systems, Abbott Malaysia and Bayer Malaysia; S.S. received personal fees from Dutch Lady during the 36 months before submitting this manuscript, outside the submitted work. C.M., C.V., C.Z., M.-L.T. and S.M. are employees of Sanofi Pasteur. The other authors have no conflicts of interest to disclose.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1.

Flow of participants through the study. *Five participants did not meet inclusion criteria or refused vaccine after randomization. †After protocol amendment, participants who were seronegative for dengue at baseline were discontinued for “noncompliance with protocol.”

FIGURE 2.

GMTs of neutralizing antibodies against HPV types 6, 11, 16 and 18 28 days after each dose of quadrivalent HPV vaccine given concomitantly or sequentially with CYD-TDV (full analysis set, dengue-seropositive participants).

FIGURE 3.

GMTs of neutralizing antibody for each dengue serotype, 28 days after each dose of CYD-TDV administered concomitantly or sequentially with quadrivalent HPV vaccine (full analysis set, dengue-seropositive participants).