Immunogenicity of an Intradermal Qdenga Vaccine Among Healthy Volunteers

As in the setting of low- to middle-income countries, to demonstrating that lower doses of vaccine via intradermal route can still elicit robust immune responses, thereby lowering the overall cost of vaccination might be particularly meaningful ,with possible extra benefit of experiencing fewer side effects or risk of allergy. This study goal is to explores the potential of intradermal administration of Qdenga, hypothesizing that a lower dose via this route could achieve adequate immunogenicity compared to the standard subcutaneous administration, thus offering a cost-effective alternative particularly in low-resource settings where dengue is most prevalent.

• Vaccine (Biological): Subcutaneous route vs Intradermal route

Primary outcomes

• Dengue IgG Level [Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination)]: To measure Antibody level for dengue by ELISA on day 0, day 30 and day 120 after 1st vaccination
• CD4 T Cell Responses [Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination)]: To measure T cell responses to dengue antigen by ELISpot on day 0, day 30 and day 120 after 1st vaccination.
• CD8 T Cell Response [Day 0 (Baseline), Day 30 (30 days post 1st vaccination) and Day 120 (30 days post 2nd vaccination)]: To measure T cell responses to dengue antigen by ELISpot on day 0, day 30 and day 120 after 1st vaccination.

Secondary outcomes

• All-Cause Mortality [at day 7 and 30 post each vaccination]: Death from any cause occurring from the first vaccination until the end of the 120-day follow-up period.
• Serious Adverse Events [at day 7 and 30 post each vaccination]: Any untoward medical occurrence during the study period that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect, regardless of its relationship to the study vaccine.
• Local Reactions [at day 7 and 30 post each vaccination]: \- Include any reported pain, swelling, erythema or nodule at the vaccination site
• Systemic Reactions [at day 7 and 30 post each vaccination]: fever, chill, fatique, headache, myalgia
• Pain at Vaccination Site, 7 Day Post 1st Vaccination [7 day post 1st vaccination]: Injection-site pain reported during the 7-day period following the first vaccine dose.
• Erythema at Vaccination Site, 7 Day Post 1st Vaccination [7 day post 1st vaccination]: Erythema at vaccination site reported during the 7-day period following the first vaccine dose.
• Malaise, 7 Day Post 1st Vaccination [7 day post 1st vaccination]: Self-reported malaise during the 7-day period following the first vaccine dose.
• Headache, 7 Day Post 1st Vaccination [7 day post 1st vaccination]: Self-reported headache during the 7-day period following the first vaccine dose.
• Erythema at Vaccination Site, 7 Day Post 2nd Vaccination [7 day post 2nd vaccination]: Erythema at vaccination site reported during the 7-day period following the second vaccine dose.

Sex: All, ages: 18 Years to 60 Years, accepts healthy volunteers

Inclusion Criteria:

* Thai adult aged 18-60 years, who not previously received dengue vaccine.
* The subjects are able to and willing to comply with the requirements of the clinical trial program and could complete the 3-month follow-up of the study.
* Individuals who are in good health condition at the time of entry into the trial as determined by medical history, physical examination and clinical judgment of the investigator and meet the requirements of immunization
* The subject can provide with informed consent and sign informed consent form

Exclusion Criteria:

* Have a medical history or family history of convulsion, epilepsy, encephalopathy and psychosis.
* Be allergic to any component of the research vaccines or used to have a history of hypersensitivity or serious reactions to vaccination.
* Women with positive urine pregnancy test, pregnant or breast-feeding, or have a pregnancy plan within six months.
* Have acute infectious diseases, including dengue infection
* Have severe chronic diseases or condition in progress cannot be controlled. For example, poor controlled DM and uncontrolled HT.
* Have the history of urticaria 1 year before receiving the investigational vaccine.
* Have known underlying diseases of thrombocytopenia or other coagulation disorders (which may cause contraindications for intramuscular injection).
* Have needle sickness.
* Have the history of immunosuppressive therapy, cytotoxic therapy or systemic corticosteroids
* Have received blood products within 4 months before injection of investigational vaccines.
* Under anti-tuberculosis treatment.
* Not be able to follow the protocol, or not be able to understand the informed consent according to the researcher's judgment, due to various medical, psychological, social or other conditions.

Participant flow

Outcome results

• Dengue IgG Level (Primary), Median, RU/ml: SC ID 108.9 (102.2 to 124.8); SC SC 104.0 (104.0 to 113.0) (p < 0.01)
• CD4 T Cell Responses (Primary), Median, SFCs per 10^6 PBMCs: SC ID 22.0 (17.8 to 81.3); SC SC 15.0 (5.0 to 38.0)
• CD8 T Cell Response (Primary), Median, SFCs per 10^6 PBMCs: SC ID 5.0 (1.8 to 38.5); SC SC 11.0 (1.0 to 47.0)
• All-Cause Mortality (Secondary), Count of participants, Participants: SC ID 0; SC SC 0
• Serious Adverse Events (Secondary), Count of participants, Participants: SC ID 0; SC SC 0
• Local Reactions (Secondary), Count of participants, Participants: SC ID 3; SC SC 1
• Systemic Reactions (Secondary), Count of participants, Participants: SC ID 0; SC SC 2
• Pain at Vaccination Site, 7 Day Post 1st Vaccination (Secondary), Count of participants, Participants: SC ID 2; SC SC 1
• Erythema at Vaccination Site, 7 Day Post 1st Vaccination (Secondary), Count of participants, Participants: SC ID 2; SC SC 0
• Malaise, 7 Day Post 1st Vaccination (Secondary), Count of participants, Participants: SC ID 0; SC SC 1
• Headache, 7 Day Post 1st Vaccination (Secondary), Count of participants, Participants: SC ID 0; SC SC 1
• Erythema at Vaccination Site, 7 Day Post 2nd Vaccination (Secondary), Count of participants, Participants: SC ID 2; SC SC 0

Adverse events

Time frame: Day 37, 60 (7 and 30 days post 1st vaccination) and Day 97, 120 (7 and 30 days post 2nd vaccination)

Other adverse events by term

Limitations and caveats: This pilot study is limited by small sample size, short follow-up, and lack of neutralization assays and detailed T-cell phenotyping. These factors restrict interpretation of durability, serotype-specific responses, and immune correlates. Larger studies with extended immunologic assessments are planned.

• Study Protocol and Statistical Analysis Plan (PDF, 2025-11-16)