Immunogenicity and safety of the live-attenuated tetravalent dengue vaccine (TAK-003) co-administered with recombinant 9-valent human papillomavirus vaccine

Abstract Background: The tetravalent dengue vaccine TAK-003 and the 9-valent human papillomavirus (9vHPV) vaccine regimens are potentially compatible, with overlapping target age groups, facilitating inclusion of TAK-003 into established immunization programs. Methods: This phase 3, open-label, randomized, multicenter trial was conducted in Thailand to investigate the immunogenicity and safety of co-administration of TAK-003 with 9vHPV in healthy participants aged ≥9 to <15 years. Participants were randomized 1:1 to either Group 1 (9vHPV + TAK-003 Month [M]0, TAK-003 M3, 9vHPV M6) or Group 2 (9vHPV M0 and M6) and followed up for 6 months after last vaccination. The primary objective was non-inferiority (NI) (upper bound of the 95 % confidence intervals for the HPV total immunoglobulin G (IgG) level ratio < 1.5) of the immune response to 9vHPV co-administered with TAK-003 versus 9vHPV alone at M7 (1 month after the last 9vHPV dose). Safety was assessed for all participants who received at least one vaccine dose. Results: The trial was completed by 606/614 (98.7 %) participants and 477/614 (77.7 %) participants were included in the per-protocol set (PPS) (Group 1 = 242; Group 2 = 235). Total HPV IgG levels for HPV types ranged from 504 to 7778 mMU/mL in Group 1 and 561–7823 mMU/mL in Group 2 at M7 and NI was demonstrated for all HPV types. Seropositivity rates at M4 were ≥ 99.6 % for all dengue serotypes. No new safety risks were identified from this trial. Conclusions: These findings support the co-administration of the TAK-003 and 9vHPV vaccines. ClinicalTrials.gov registration number: NCT04313244.