Phase IV Study on Serological Cross-Reactivity in Flavivirus Diagnostics Post-Vaccination with Dengue Tetravalent Vaccine (Live, Attenuated) in Swedish Travelers

The primary objective of this phase IV clinical trial is to evaluate whether the **Qdenga** vaccine leads to significantly elevated levels of cross-reactive IgG antibody levels against tick-borne encephalitis virus (TBEV), yellow fever virus (YFV), Zika virus (ZIKV), and Japanese encephalitis virus (JE) at day 90 following the administration of two doses of the vaccine, compared to levels before vaccination. This assessment is clinically relevant as it addresses potential cross-reactivity in serological diagnostics of flavivirus infections, which is crucial for accurate diagnosis and management of these infections in individuals vaccinated with the dengue vaccine.

The clinical trial involves a study population comprising **healthy adults** aged 18 years and older, with both **male and female** participants included. The trial is focused on individuals without any pre-existing medical conditions, as it is a prophylactic study for a vaccine against **dengue fever**. Participants are required to be planning travel to a dengue-endemic region, which is a significant lifestyle consideration. The selection criteria include the ability to participate in all study components and the provision of signed informed consent. Women of childbearing potential must have a negative pregnancy test. The sponsor has not provided the total number of participants involved in the trial.

The clinical trial is designed as an **open non-randomized phase IV trial** to evaluate the potential cross-reactivity in serological diagnostics of flavivirus infections following vaccination with the live dengue vaccine, Qdenga. The primary objective is to assess whether the Qdenga vaccine causes significantly elevated levels of cross-reactive **IgG antibody** levels against tick-borne encephalitis virus (TBEV), yellow fever virus (YFV), Zika virus (ZIKV), and Japanese encephalitis virus (JE) at day 90 after two doses of Qdenga compared to before vaccination. The trial is expected to commence recruitment on September 1, 2025, and conclude by November 1, 2027.

Participants will be involved in the study for a period of approximately 90 days. The study will include several key visits: an initial **screening visit** to determine eligibility based on criteria such as age (18 years or older), ability to participate, and a negative pregnancy test for women of childbearing potential. Participants must also plan to travel to a dengue fever endemic country. Following the screening, participants will receive two doses of the vaccine, administered via **subcutaneous injection**, with a maximum total dose of 1 ml. The primary endpoint will be measured at a follow-up visit on day 90, where IgG antibody levels will be assessed.

The trial will involve a series of study visits, including the initial screening, vaccination visits, and a follow-up visit at day 90. The end-of-study visit will coincide with the final follow-up, where the primary endpoint will be evaluated. Participants may be withdrawn from the study if they fail to meet the inclusion criteria, experience adverse reactions, or choose to withdraw consent. The trial is categorized as low intervention, given its prophylactic nature and the use of an authorized vaccine. The study aims to provide valuable insights into the serological impact of the Qdenga vaccine on cross-reactive antibody levels in individuals traveling to dengue-endemic regions.

The clinical trial involves the administration of **Qdenga**, a powder and solvent for solution for injection, which is a **dengue tetravalent vaccine** (live, attenuated). The vaccine is designed to provide immunization against dengue virus and is composed of live, attenuated viruses. The active substances include **Dengue virus, serotype 2, live, attenuated**, and serotype 2 expressing surface proteins of serotypes 1, 3, and 4, all live and attenuated. These components are identified by the synonyms TDV-2, TDV-1, TDV-3, and TDV-4, respectively. The vaccine is administered via **subcutaneous injection**. The dosage regimen consists of two doses, each with a maximum daily dose of 0.5 ml, and a total maximum dose of 1 ml over a treatment period of 2 months.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the Qdenga vaccine to assess its effects on cross-reactive IgG antibody levels against other flaviviruses, including TBEV, YFV, ZIKV, and JE. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to evaluate the immunological response at day 90 following the administration of the two doses of the vaccine.

Efficacy in this clinical trial will be assessed by measuring the levels of cross-reactive **IgG antibodies** against tick-borne encephalitis virus (TBEV), yellow fever virus (YFV), Zika virus (ZIKV), and Japanese encephalitis virus (JE) in serum. The primary endpoint is the comparison of these **IgG antibody** levels at day 90 after administration of two doses of the Qdenga vaccine, relative to levels before vaccination. This assessment aims to determine if the Qdenga vaccine causes significantly elevated levels of cross-reactive **IgG antibodies** against these flaviviruses.